掲載種別：研究論文（学術雑誌）   出版者・発行元：Medical Association of Nippon Medical School  

DOI： 10.1272/manms.19.84

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

microRNAs (miRNAs) are extracellularly released by cells for intercellular communication, while intracellularly, they inhibit the expression of specific genes. An increasing number of studies suggest that extracellular miRNAs have great potential as both therapeutic targets and disease-specific biomarkers in a variety of diseases, including pain disorders. However, little is known about miRNA release from dorsal root ganglion (DRG) neurons in neuropathic pain caused by peripheral nerve injury. In this study, we investigated the changes in the extracellular release of miRNAs from DRG neurons in a rat model of neuropathic pain induced by chronic constriction injury of the sciatic nerve. We found increased release of six miRNAs (let-7d, miR-21, miR-142-3p, miR-146b, miR-203-3p and miR-221) from primary cultured DRG neurons prepared from rats 7 days after nerve injury. Among these, miR-221 was also increased in serum from days 7 to 28 after nerve injury. In contrast, serum miR-221 levels and its release from DRG neurons were unchanged in an inflammatory pain model produced by intraplantar injection of complete Freund's adjuvant. These results suggest that the increased release of specific miRNAs by DRG neurons may be involved in the pathophysiology of neuropathic pain through extracellular as well as intracellular mechanisms. Furthermore, serum miR-221 may be useful as a biomarker of neuropathic pain caused by peripheral nerve injury.

DOI： 10.1371/journal.pone.0280425

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Heparin anticoagulation increases the bleeding risk during extracorporeal life support (ECLS). This study determined whether factor XII (FXII) silencing using short interfering RNA (siRNA) can provide ECLS circuit anticoagulation without bleeding. Adult male, Sprague-Dawley rats were randomized to four groups (n = 3 each) based on anticoagulant: (1) no anticoagulant, (2) heparin, (3) FXII siRNA, or (4) nontargeting siRNA. Heparin was administered intravenously before and during ECLS. FXII or nontargeting siRNA were administered intravenously 3 days before the initiation of ECLS via lipidoid nanoparticles. The rats were placed on pumped, arteriovenous ECLS for 8 hours or until the blood flow resistance reached three times its baseline resistance. Without anticoagulant, mock-oxygenator resistance tripled within 7 ± 2 minutes. The resistance in the FXII siRNA group did not increase for 8 hours. There were no significant differences in resistance or mock-oxygenator thrombus volume between the FXII siRNA and the heparin groups. However, the bleeding time in the FXII siRNA group (3.4 ± 0.6 minutes) was significantly shorter than that in the heparin group (5.5 ± 0.5 minutes, p < 0.05). FXII silencing using siRNA provided simpler anticoagulation of ECLS circuits with reduced bleeding time as compared to heparin.

DOI： 10.1097/MAT.0000000000001876

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Postoperative acute kidney injury (AKI) is a highly prevalent and serious complication after cardiac surgery. The aim of this study is to identify the predictors of AKI and the cut-off values after isolated off-pump coronary artery bypass grafting (OPCAB). A total of 329 adult patients, who underwent isolated OPCAB between December 2008 and February 2021, were retrospectively analyzed. The patients were divided into three groups: non-AKI, early AKI and late AKI groups. The early AKI group or the late AKI group were defined as 'having AKI that occurred before or after 48 h postoperatively', respectively. Multivariate logistic regression analysis was performed to identify the predictors of AKI. Receiver operating characteristic (ROC) curve analysis was used to evaluate the cutoff value, the sensitivity, and the specificity of the predictors. On the multivariate analysis, the emergency surgery, the preoperative serum albumin, and the postoperative day 1 neutrophil to lymphocyte ratio (NL ratio) were identified as the independent predictors of AKI. However, neither albumin nor the NL ratio predicted late AKI. The present study showed the preoperative albumin and the postoperative day 1 NL ratio were the robust and independent predictors of postoperative early AKI in isolated OPCAB.

DOI： 10.1038/s41598-022-19772-7

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

INTRODUCTION: Oxygenator exchange during extracorporeal membrane oxygenation (ECMO) is a life-threatening procedure. D-dimer has been used to predict oxygenator failure, but it is a parameter used a few days before oxygenator exchange. This study investigated parameters before and immediately after ECMO initiation that predict oxygenator exchange. METHODS: This was a single-center, retrospective study of 28 patients who received veno-venous ECMO with heparin/silicone-coated polypropylene oxygenator (NSH-R HPO-23WH-C; Senko Medical Inc., Tokyo, Japan), due to acute respiratory failure, from April 2015 to March 2020. Clinical data before ECMO initiation and during the first 3 days on ECMO were compared between the patients with oxygenator exchange (exchange group) and those without oxygenator exchange (non-exchange group). RESULTS: Nine (32%) patients required oxygenator exchange. The exchange group had significantly higher white blood cell count (WBC) (16,944 ± 2423/µL vs 10,342 ± 1442/µL, p < 0.05) and Acute Physiology and Chronic Health Evaluation (APACHE) II score (31 ± 5 vs 25 ± 8, p < 0.05) before ECMO initiation than the non-exchange group. The partial pressure of oxygen at the outlet of the oxygenator (PO2 outlet) and activated partial thromboplastin time (aPTT) during the first 3 days on ECMO were significantly lower in the exchange group than in the non-exchange group. CONCLUSIONS: High WBC and APACHE II score before ECMO initiation, low PO2 outlet, and aPTT during the first 3 days on ECMO were associated with oxygenator exchange during veno-venous ECMO. These parameters could be used to avoid unexpected oxygenator exchange.

DOI： 10.1177/03913988221118382

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Anaesthetics may modify colorectal cancer cell biology which potentially affects long-term survival. This study aims to compare propofol and sevoflurane regarding with the direct anaesthetic effects on cancer malignancy and the indirect effects on host immunity in a cancer xenograft mode of mice. Cultured colon cancer cell (Caco-2) was injected subcutaneously to nude mice (day 1). Mice were exposed to either 1.5% sevoflurane for 1.5 h or propofol (20 μg g-1; ip injection) with or without 4 μg g-1 lipopolysaccharide (LPS; ip) from days 15 to 17, compared with those without anaesthetic exposure as controls. The clinical endpoints including tumour volumes over 70 mm3 were closely monitored up to day 28. Tumour samples from the other cohorts were collected on day 18 for PCR array, qRT-PCR, western blotting and immunofluorescent assessment. Propofol treatment reduced tumour size (mean ± SD; 23.0 ± 6.2mm3) when compared to sevoflurane (36.0 ± 0.3mm3) (p = 0.008) or control (23.6 ± 4.7mm3). Propofol decreased hypoxia inducible factor 1α (HIF1α), interleukin 1β (IL1β), and hepatocyte growth factor (HGF) gene expressions and increased tissue inhibitor of metalloproteinases 2 (TIMP-2) gene and protein expression in comparison to sevoflurane in the tumour tissue. LPS suppressed tumour growth in any conditions whilst increased TIMP-2 and anti-cancer neutrophil marker expressions and decreased macrophage marker expressions compared to those in the LPS-untreated groups. Our data indicated that sevoflurane increased cancer development when compared with propofol in vivo under non-surgical condition. Anaesthetics tested in this study did not alter the effects of LPS as an immune modulator in changing immunocyte phenotype and suppressing cancer development.

DOI： 10.1007/s10565-022-09747-9

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Klippel-Trenaunay-Weber syndrome (KTWS) is a rare congenital malformation. Although there have been few reports on anaesthetic management of patients with KTWS, there is a lack of data on anaesthetic management for abdominal aortic aneurysm (AAA) surgeries in these patients. CASE PRESENTATION: A 74-year-old man (height, 160 cm and body weight, 51.5 kg) with KTWS was scheduled for AAA replacement. Abdominal computed tomography (CT) showed prominent tortuosity below the abdominal aorta with an infrarenal abdominal aortic aneurysm, right common iliac artery aneurysm, and right external iliac artery aneurysm. Moreover, a remarkably noted arteriovenous fistula had developed between the aneurysm and peripheral artery. General anaesthesia was induced. Furthermore, a central venous catheter and an 8.5 French sheath in the left internal jugular vein were inserted. During the operation, bleeding from a collateral vessel in the cross-clamped aorta led the surgeon to decide to perform aneurysmorrhaphy. Intraoperatively, blood loss was 1500 ml, and 20 units of red blood cell concentrate were used. CONCLUSIONS: Regarding AAA procedures in patients with KTWS, aortic cross-clamping may not sufficiently intercept blood flow due to collateral vessels. In these patients, the anaesthesiologist must be prepared to transfuse blood more rapidly and frequently than during normal AAA procedures.

DOI： 10.1186/s12871-022-01761-y

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

In Japan, successful cases of a bridge to lung transplantation (BTT) by extracorporeal membrane oxygenation (ECMO) are rare. We present the case of a man in his thirties, diagnosed with interstitial pneumonia 6 years prior and registered for lung transplant 1 year prior due to disease progression despite treatment. Due to the patient's worsening respiratory failure, he was transferred to our hospital for BTT by ECMO. Since long-term management was expected and pulmonary hypertension was present, veno-arterial (V-A) ECMO was conducted using the right atrial blood outflow via the right internal jugular vein and right axillary artery inflow via a vascular graft. After tracheostomy, he was managed as "Awake ECMO". In addition, interprofessional collaboration such as physiotherapist rehabilitation, nurses, and liaison teams prevented muscle weakness and supported the mental aspect. We were able to minimize complications such as severe infections and bleeding. A compatible brain-dead donor was found on day 108 after introducing ECMO, and the patient was transferred to a transplant facility on day 109. The peripheral upper V-A ECMO is one of the configurations suitable for long-term BTT management.

DOI： 10.1007/s10047-022-01341-4

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Wiley  

Lung endothelial permeability is a key pathological feature of acute respiratory distress syndrome. Hyaluronic acid (HA), a major component of the glycocalyx layer on the endothelium, is generated by HA synthase (HAS) during inflammation and injury and is critical for repair. We hypothesized that administration of exogenous high molecular weight (HMW) HA would restore protein permeability across human lung microvascular endothelial cells (HLMVEC) injured by an inflammatory insult via upregulation of HAS by binding to CD44. A transwell coculture system was used to study the effects of HA on protein permeability across HLMVEC injured by cytomix, a mixture of IL-1β, TNFα, and IFNγ, with or without HMW or low molecular weight (LMW) HA. Coincubation with HMW HA, but not LMW HA, improved protein permeability following injury at 24 h. Fluorescence microscopy demonstrated that exogenous HMW HA partially prevented the increase in "actin stress fiber" formation. HMW HA also increased the synthesis of HAS2 mRNA expression and intracellular HMW HA levels in HLMVEC following injury. Pretreatment with an anti-CD44 antibody or 4-methylumbelliferone, a HAS inhibitor, blocked the therapeutic effects. In conclusion, exogenous HMW HA restored protein permeability across HLMVEC injured by an inflammatory insult in part through upregulation of HAS2.

DOI： 10.1096/fba.2022-00006

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: The concept of "see one, do one, teach one" raises concerns regarding patient safety in the intensive care unit (ICU) and highlights the need for prior preparation of residents/fellows for ICU rotation. This study assessed the need for an adult pre-ICU "boot camp" training course. METHODS: An online questionnaire regarding the current ICU training and desirable course framework was distributed via e-mail to the ICU directors of 269 educational centers certified by the Japanese Society of Intensive Care Medicine. RESULTS: The response rate was 39% (106/269). The number of residents/fellows undergoing ICU rotation was 5.5 (IQR 2-12) /ICU/year, and the majority (63%) were second to fourth year post-graduate residents and fellows. ICU directors opined that of the fundamental critical care skills, residents/fellows performed well or very well in only seven out of 29 skills (24%). Only 18% of the ICU directors had an established ICU training curriculum. Overall, 72% of the directors were interested in the boot camp. The desirable course framework was 3-5 hours per day with simulations and lectures. The core skills that directors considered as important to acquire during ICU rotation were central venous catheter insertion, tracheal intubation, defibrillation, initiation of mechanical ventilation, physical examination of critically ill patients, and shock assessment. CONCLUSIONS: Residents/fellows began ICU rotations with suboptimal skills as reported by ICU directors. In addition, most of the ICUs had not established a training curriculum. Therefore, having an ICU boot camp is necessary to enhance critical care skills and to decrease medical errors.

DOI： 10.1272/jnms.JNMS.2022_89-412

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The suprachiasmatic nucleus (SCN) of the hypothalamus is a nucleus that regulates circadian rhythms through the cyclic expression of clock genes. It has been suggested that circadian-rhythm-related, adverse postoperative events, including sleep disturbances and delirium, are partly caused by anesthesia-induced disruption of clock-gene expression. We examined the effects of multiple general anesthetics on the expression cycle of Period2 (Per2), one of the clock genes that regulate circadian rhythms in the SCN, and on the behavioral rhythms of animals. Rats were treated with sevoflurane, propofol, and dexmedetomidine for 4 h. The expression of Per2 in SCN was analyzed using in situ hybridization, and the behavioral rhythm before and after anesthesia was analyzed. Per2 expression in the SCN decreased significantly immediately after anesthesia in all groups compared with corresponding control groups. However, Per2 returned to normal levels within 24 h, and there was no phase change in the gene expression cycle or behavioral rhythm. This study suggests that acute suppression of Per2 expression may be a general phenomenon induced by general anesthesia, but that the molecular mechanism of the body clock is resilient to disturbances to some extent.

DOI： 10.1007/s00418-022-02113-0

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

General anesthetics have different efficacies and side effect incidences based on their mechanism of action. However, detailed comparative studies of anesthetics are incomplete. In this study, target brain regions and gene expression changes in these brain regions were determined for sevoflurane and propofol to understand the mechanisms that cause differences among anesthetics. Rats were anesthetized with sevoflurane or propofol for 1 hr, and brain regions with anesthesia-induced changes in neuronal activity were examined by immunohistochemistry and in situ hybridization for c-Fos. Among the identified target brain regions, gene expression analysis was performed in the habenula, the solitary nucleus and the medial vestibular nucleus from laser microdissected samples. Genes altered by sevoflurane and propofol were different and included genes involved in the incidence of postoperative nausea and vomiting and emergence agitation, such as Egr1 and Gad2. GO enrichment analysis showed that the altered genes tended to be evenly distributed in all functional category. The detailed profiles of target brain regions and induced gene expression changes of sevoflurane and propofol in this study will provide a basis for analyzing the effects of each anesthetic agent and the risk of adverse events.

DOI： 10.1267/ahc.21-00091

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background: Only a few studies have been reported on the use of dexmedetomidine for sedating surgical patients requiring epidural or spinal anesthesia. We conducted a randomized, double-blind, placebo-controlled, parallel-group study at 12 hospitals in Japan. Methods: Adult patients were randomly allocated to receive an intravenous administration of placebo or dexmedetomidine at 0.067, 0.25, 0.5 or 1.0 µg/kg over 10 min after epidural or spinal anesthesia. All dexmedetomidine groups received dexmedetomidine 0.2-0.7 µg/kg/h to maintain an Observer's Assessment of Alertness/Sedation Scale (OAA/S) score of ≤ 4; however, propofol was administered to rescue patients who exceeded this score. Surgery was then started 15 min after study drug infusion in patients with OAA/S score of ≤ 4. The primary endpoint was the percentage of patients not requiring rescue propofol to achieve and maintain an OAA/S score of ≤ 4. Results: Of the 120 enrolled and randomized patients, 119 were treated the study: 22 received placebo and 97 received dexmedetomidine (23-25 patients per dose). Significantly more patients did not require propofol in the dexmedetomidine 0.5 and 1.0 µg/kg groups (68.0% and 80.0%, respectively) compared to the placebo group (22.7%) (P = 0.003 and P < 0.001, respectively). Common adverse events (AEs) were protocol-defined respiratory depression, bradycardia and hypotension. There was no significant difference in the incidence of AEs between the dexmedetomidine and the placebo groups. Conclusion: We concluded that loading doses of 0.5 and 1.0 µg/kg dexmedetomidine, followed by an infusion at a rate of 0.2-0.7 µg/kg/h, provide effective and well-tolerated sedation for surgical patients during epidural or spinal anesthesia. Clinical trials.gov identifier: NCT01438957.

DOI： 10.33160/yam.2022.02.002

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Previous studies have shown that the liquid gastric emptying mainly depended on energy content, regardless of compositional differences. But the gastric emptying of alcoholic beverages remains unclear. Therefore, we performed the present study to compare gastric emptying times between whisky mixed with water and glucose solution with uniform energy contents and volumes. As a crossover study, 10 healthy male volunteers ingested one of 3 test solutions with a uniform volume of 150 ml, i.e., whisky with water-containing whisky 30 ml (67 kcal), sugar water containing glucose 16.8 g (67 kcal), and water (0 kcal), and the gastric emptying time of each beverage was then assessed by ultrasound measurements of the gastric antral cross-sectional area. The gastric emptying pattern of whisky with water was faster than that of isocaloric sugar water, but slower than that of water. Each antral cross-sectional area 20, 30, and 40 min after the ingestion of sugar water was significantly larger than that of whisky with water. Antral cross-sectional areas 10 and 20 min after the ingestion of water were significantly smaller than those of whisky with water. In conclusion, the gastric emptying time of whisky would be faster than that of isocaloric glucose solution and slower than that of water. Unlike the other beverages, the gastric emptying time of alcohol drinks does not purely depend on the energy content because alcohol itself has no calorie before absorption. This study is registered with the University Hospital Medical Information Network (UMIN) Clinical Trials Registry (UMIN000034443).

DOI： 10.1155/2022/6137230

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SAGE Publications  

Oxaliplatin, a platinum-based chemotherapeutic agent, frequently causes severe neuropathic pain typically encompassing cold allodynia and long-lasting mechanical allodynia. Endothelin has been shown to modulate nociceptive transmission in a variety of pain disorders. However, the action of endothelin varies greatly depending on many variables, including pain causes, receptor types (endothelin type A (ET_A) and B (ET_B) receptors) and organs (periphery and spinal cord). Therefore, in this study, we investigated the role of endothelin in a Sprague–Dawley rat model of oxaliplatin-induced neuropathic pain. Intraperitoneal administration of bosentan, a dual ET_A/ET_B receptor antagonist, effectively blocked the development or prevented the onset of both cold allodynia and mechanical allodynia. The preventive effects were exclusively mediated by ET_A receptor antagonism. Intrathecal administration of an ET_A receptor antagonist prevented development of long-lasting mechanical allodynia but not cold allodynia. In marked contrast, an intraplantar ET_A receptor antagonist had a suppressive effect on cold allodynia but only had a partial and transient effect on mechanical allodynia. In conclusion, ET_A receptor antagonism effectively prevented long-lasting mechanical allodynia through spinal and peripheral actions, while cold allodynia was prevented through peripheral actions.

DOI： 10.1177/17448069211058004

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その他リンク： http://journals.sagepub.com/doi/full-xml/10.1177/17448069211058004

記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: A growing number of older patients are undergoing surgeries. The reliable pre-operative predictive factors of surgical mortality among older patients remained unclear. This study compared the predictive factors for 30-day survival in patients over 90 years old after their non-cardiac surgery. METHODS: A retrospective study at Nippon Medical School hospital was performed for patients aged >90 years who underwent non-cardiac surgeries between 2010 and 2020. Measurements included age, gender, American Society of Anesthesiologists physical status (ASA-PS), pre-operative Charlson score, pre-operative fall risk assessment, Eastern Cooperative Oncology Group performance status (ECOG-PS), the modified 5-item frailty index (mFI-5), the presence of intra-operative transfusion, post-operative complications, and 30-day survival post-surgery. RESULTS: A total of 327 cases of elective surgery and 149 cases of emergency surgery were examined. The non-survival group (n=20, 4.2%) had significantly worse pre-operative ASA-PS in emergency cases (non-survival vs. survivor group, 2.8 [2-3] vs. 2.3 [1-4], p=0.045), ECOG-PS (3.0 [2-4] vs. 1.0 [0-4], p<0.001), and mFI-5 values (3.0 [1-4] vs. 1.0 [0-3], p<0.001), more emergency cases (75.0% vs. 36.2%, p=0.004), and a greater need for intra-operative transfusion (55.0% vs. 13.4%, p<0.001). Among the frailty assessment methods, ECOG-PS was the most efficient for 30-day mortality (area under curve, ECOG-PS: 0.98, p<0.001; mFI-5: 0.86, p<0.001; Charlson score: 0.53, p=0.71; fall risk assessment: 0.55, p=0.44). Kaplan-Maier curves and a multivariate logistic regression analysis demonstrated that ECOG-PS>3 was significantly associated with 30-day mortality (ECOG-PS: Kaplan-Maier curve, p<0.001, Log-rank test; odds ratio 1.71, 95%CI: 1.35-2.16, p<0.001). CONCLUSIONS: After non-cardiac surgery in patients >90 years old, ECOG-PS>3 was significantly correlated with 30-day mortality.

DOI： 10.1272/jnms.JNMS.2022_89-304

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記述言語：日本語   出版者・発行元：(一社)日本心臓血管麻酔学会  

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記述言語：日本語   出版者・発行元：日本臨床麻酔学会  

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記述言語：日本語   出版者・発行元：日本臨床麻酔学会  

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記述言語：日本語   出版者・発行元：日本臨床麻酔学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

INTRODUCTION: We previously reported that extracellular vesicles (EVs) released during Escherichia coli bacterial pneumonia were inflammatory, and administration of high molecular weight hyaluronic acid (HMW HA) suppressed several indices of acute lung injury (ALI) from Escherichia coli pneumonia by binding to these inflammatory EVs. The current study was undertaken to study the therapeutic effects of HMW HA in ex vivo perfused human lungs injured with Pseudomonas aeruginosa (PA)103 bacterial pneumonia. METHODS: For lungs with baseline alveolar fluid clearance (AFC)<10%/h, HMW HA 1 or 2 mg was injected intravenously after 1 h (N = 4-9), and EVs released during PA pneumonia were collected from the perfusate over 6 h. For lungs with baseline AFC>10%/h, HMW HA 2 mg was injected intravenously after 1 h (N = 6). In vitro experiments were conducted to evaluate the effects of HA on inflammation and bacterial phagocytosis. RESULTS: For lungs with AFC<10%/h, administration of HMW HA intravenously significantly restored AFC and numerically decreased protein permeability and alveolar inflammation from PA103 pneumonia but had no effect on bacterial counts at 6 h. However, HMW HA improved bacterial phagocytosis by human monocytes and neutrophils and suppressed the inflammatory properties of EVs released during pneumonia on monocytes. For lungs with AFC>10%/h, administration of HMW HA intravenously improved AFC from PA103 pneumonia but had no significant effects on protein permeability, inflammation or bacterial counts. DISCUSSION: In the presence of impaired alveolar epithelial transport capacity, administration of HMW HA improved the resolution of pulmonary edema from Pseudomonas PA103 bacterial pneumonia.

DOI： 10.1152/ajplung.00626.2020

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

INTRODUCTION: The successful use of prolonged (i.e., > 28 days) veno-venous extracorporeal membrane oxygenation (V-V ECMO) is being increasingly reported. However, limited data is available on its outcomes. This study investigated the outcomes of acute respiratory distress syndrome (ARDS) patients on prolonged ECMO support. METHODS: We retrospectively evaluated 57 patients requiring V-V ECMO for ARDS between 2015 and 2020. The patients were divided into two groups according to ECMO duration: (i) ≤ 28 days group (n = 43, 75%), or (ii) > 28 days (n = 14, 25%) group. Clinical characteristics, complications, and outcomes between these two groups were statistically compared. RESULTS: There were no significant differences in demographics, comorbidity, ARDS etiology and severity scores between the two groups. However, the mechanical ventilation period before ECMO initiation was significantly longer in the > 28 days group than in the ≤ 28 days group (10.5 days vs. 1 day; P < .05). The incidence of positive bacterial blood culture results during ECMO was significantly higher in the > 28 days group than in the ≤ 28 days group (43% vs. 9%; P < .05). Additionally, the hospital survival rate was significantly lower in the > 28 days group than in the ≤ 28 days ECMO group (21% vs. 60%; P < .05). CONCLUSION: Prolonged ECMO was associated with worse hospital survival outcomes. Early initiation of ECMO along with meticulous care and appropriate treatment against infection during ECMO could improve the hospital survival of ARDS patients on prolonged ECMO support.

DOI： 10.1111/aor.14051

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記述言語：日本語   出版者・発行元：(一社)日本ペインクリニック学会  

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記述言語：日本語   出版者・発行元：(一社)日本ペインクリニック学会  

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記述言語：日本語   出版者・発行元：(一社)日本ペインクリニック学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) research using large animals requires a significant amount of resources, slowing down the development of new means of ECMO anticoagulation. Therefore, this study developed and evaluated a new rat ECMO model using a 3D-printed mock-oxygenator. METHODS: The circuit consisted of tubing, a 3D-printed mock-oxygenator, and a roller pump. The mock-oxygenator was designed to simulate the geometry and blood flow patterns of the fiber bundle in full-scale oxygenators but with a low (2.5 mL) priming volume. Rats were placed on arteriovenous ECMO at a 1.9 mL/min flow rate at two different heparin doses (n = 3 each): low (15 IU/kg/h for eight hours) versus high (50 IU/kg/h for one hour followed by 25 IU/kg/h for seven hours). The experiment continued for eight hours or until the mock-oxygenator failed. The mock-oxygenator was considered to have failed when its blood flow resistance reached three times its baseline resistance. RESULTS: During ECMO, rats maintained near-normal mean arterial pressure and arterial blood gases with minimal hemodilution. The mock-oxygenator thrombus weight was significantly different (p < 0.05) between the low (0.02 ± 0.006 g) and high (0.003 ± 0.001 g) heparin delivery groups, and blood flow resistance was also larger in the low anticoagulation group. CONCLUSIONS: This model is a simple, inexpensive system for investigating new anticoagulation agents for ECMO and provides low and high levels of anticoagulation that can serve as control groups for future studies.

DOI： 10.1186/s12967-021-02847-w

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Inhalational anesthetics was previously reported to suppress glioma cell malignancy but underlying mechanisms remain unclear. The present study aims to investigate the effects of sevoflurane and desflurane on glioma cell malignancy changes via microRNA (miRNA) modulation. The cultured H4 cells were exposed to 3.6% sevoflurane or 10.3% desflurane for 2 h. The miR-138, -210 and -335 expression were determined with qRT-PCR. Cell proliferation and migration were assessed with wound healing assay, Ki67 staining and cell count kit 8 (CCK8) assay with/without miR-138/-210/-335 inhibitor transfections. The miRNA downstream proteins, hypoxia inducible factor-1α (HIF-1α) and matrix metalloproteinase 9 (MMP9), were also determined with immunofluorescent staining. Sevoflurane and desflurane exposure to glioma cells inhibited their proliferation and migration. Sevoflurane exposure increased miR-210 expression whereas desflurane exposure upregulated both miR-138 and miR-335 expressions. The administration of inhibitor of miR-138, -210 or -335 inhibited the suppressing effects of sevoflurane or desflurane on cell proliferation and migration, in line with the HIF-1α and MMP9 expression changes. These data indicated that inhalational anesthetics, sevoflurane and desflurane, inhibited glioma cell malignancy via miRNAs upregulation and their downstream effectors, HIF-1α and MMP9, downregulation. The implication of the current study warrants further study.

DOI： 10.3390/ijms22094355

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: microRNAs (miRNAs) are single-stranded and noncoding RNA molecules that control post-transcriptional gene regulation. miRNAs can be tumor suppressors or oncogenes through various mechanism including cancer cell biology, cell-to-cell communication, and anti-cancer immunity. MAIN BODY: Anesthetics can affect cell biology through miRNA-mediated regulation of messenger RNA (mRNA). Indeed, sevoflurane was reported to upregulate miR-203 and suppresses breast cancer cell proliferation. Propofol reduces matrix metalloproteinase expression through its impact on miRNAs, leading to anti-cancer microenvironmental changes. Propofol also modifies miRNA expression profile in circulating extracellular vesicles with their subsequent anti-cancer effects via modulating cell-to-cell communication. CONCLUSION: Inhalational and intravenous anesthetics can alter cancer cell biology through various cellular signaling pathways induced by miRNAs' modification. However, this area of research is insufficient and further study is needed to figure out optimal anesthesia regimens for cancer patients.

DOI： 10.1186/s12871-021-01294-w

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Inhalational anaesthetics were previously reported to promote ovarian cancer malignancy, but underlying mechanisms remain unclear. The present study aims to investigate the role of sevoflurane- or desflurane-induced microRNA (miRNA) changes on ovarian cancer cell behaviour. The cultured SKOV3 cells were exposed to 3.6% sevoflurane or 10.3% desflurane for 2 h. Expression of miR-138, -210 and -335 was determined with qRT-PCR. Cell proliferation and migration were assessed with wound healing assay, Ki67 staining and Cell Counting Kit-8 (CCK8) assay with or without mimic miR-138/-210 transfections. The miRNA downstream effector, hypoxia inducible factor-1α (HIF-1α), was also analysed with immunofluorescent staining. Sevoflurane or desflurane exposure to cancer cells enhanced their proliferation and migration. miR-138 expression was suppressed by both sevoflurane and desflurane, while miR-210 expression was suppressed only by sevoflurane. miR-335 expression was not changed by either sevoflurane or desflurane exposure. The administration of mimic miR-138 or -210 reduced the promoting effects of sevoflurane and desflurane on cancer cell proliferation and migration, in line with the HIF-1α expression changes. These data indicated that inhalational agents sevoflurane and desflurane enhanced ovarian cancer cell malignancy via miRNA deactivation and HIF-1α. The translational value of this work needs further study.

DOI： 10.3390/ijms22041826

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The widespread occurrence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to a pandemic of coronavirus disease 2019 (COVID-19). The S spike protein of SARS-CoV-2 binds with angiotensin-converting enzyme 2 (ACE2) as a functional "receptor" and then enters into host cells to replicate and damage host cells and organs. ACE2 plays a pivotal role in the inflammation, and its downregulation may aggravate COVID-19 via the renin-angiotensin system, including by promoting pathological changes in lung injury and involving inflammatory responses. Severe patients of COVID-19 often develop acute respiratory distress syndrome and multiple organ dysfunction/failure with high mortality that may be closely related to the hyper-proinflammatory status called the "cytokine storm." Massive cytokines including interleukin-6, nuclear factor kappa B (NFκB), and tumor necrosis factor alpha (TNFα) released from SARS-CoV-2-infected macrophages and monocytes lead inflammation-derived injurious cascades causing multi-organ injury/failure. This review summarizes the current evidence and understanding of the underlying mechanisms of SARS-CoV-2, ACE2 and inflammation co-mediated multi-organ injury or failure in COVID-19 patients.

DOI： 10.1007/s10753-020-01337-3

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE: The purpose of this pre-post survey study was to assess the effect of the Patient SafetyNet system (Masimo Corp, Irvine, CA) on postoperative respiratory evaluation by nurses in general wards. Patient SafetyNet is a wireless monitoring system that evaluates respiratory rate and percutaneous oxygen saturation. DESIGN: Survey of nurses at a single medical center. METHODS: Staff nurses (n = 75) were queried using a questionnaire asking about methods and problems of postoperative respiratory monitoring, usefulness of this system, and suggestions about suitable cases of this system. FINDINGS: A total of 75 questionnaires were completed and returned. The nurses reported that central/remote (89.3%) or continuous (98.7%) monitoring was useful in the postquestionnaire. Moreover, the average frequency of clinical examination was reduced from 11.0 ± 2.3 to 5.1 ± 1.3. Using the Patient SafetyNet system led to a reported 61.3% reduction in nursing workload related to respiratory assessment postoperatively. CONCLUSIONS: Continuous monitoring of respiratory rate and percutaneous oxygen saturation after general anesthesia is recommended for patients' safety. Moreover, Patient SafetyNet can decrease the number of physical assessments of respiratory status for postoperative patients in the general wards, resulting in reduction of nurse's workload.

DOI： 10.1016/j.jopan.2020.03.005

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記述言語：英語  

Budd-Chiari syndrome (BCS) is a rare congestive hepatopathy arising from hepatic venous outflow obstruction. The clinical presentation of BCS varies depending on the presence of collateral veins. The authors report a rare case of infective endocarditis and chronic primary BCS in a 50-year-old man who underwent open cardiac surgery. Due to the presence of dilated collateral veins flowing directly into the inferior vena cava, cardiopulmonary bypass was established by arterial cannulation of the ascending aorta, with venous cannulation of the upper portion of the superior vena cava, as well as the dilated collateral vein. Mitral valve replacement and tricuspid valvuloplasty were performed uneventfully, and the patient then was admitted to the intensive care unit. Patients with primary BCS need to be evaluated rigorously preoperatively and intraoperatively for collateral flow to establish cardiopulmonary bypass.

DOI： 10.1053/j.jvca.2020.11.063

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Postoperative pain management in thoracotomy patients often is difficult. Furthermore, pediatric patients present more challenges because of their inability to effectively communicate their pain intensity. The purpose of this study was to evaluate the use of continuous field block through intercostal muscles as postoperative pain management in pediatric thoracotomy. METHODS: Between 2014 and 2018, 11 patients underwent an ASD closure using a cardiopulmonary bypass via a mini-right thoracotomy through the fourth intercostal space. At the time of chest closure, a single-shot field block via the fourth intercostal muscles was performed with levobupivacaine (0.6 mg/kg). The first five patients were only given the single-shot field block (Single group). The remaining six patients were given levobupivacaine continuously (0.1 mg/kg/hr) through an indwelling catheter until the chest tube removal (Continuous group). The groups' vital signs, total amounts of acetaminophen used, postoperative courses were compared. RESULTS: Although the heart rate did not differ between the groups, the respiratory rate was significantly higher in the Single group versus the Continuous group at 16 and 32 hr post-surgery (35.6±9.7/min vs. 18.5±4.7/min; p=0.007, 43.0±10.4 vs. 25.3±3.1; p=0.042, respectively). The accumulated dosage of acetaminophen given by postoperative day 2 was significantly higher in the Single group versus the Continuous group (55.3±22.1 mg/kg vs. 7.8±17.4 mg/kg; p=0.012). CONCLUSIONS: Continuous field block via intercostal muscles after ASD closure via a mini-right thoracotomy in children was effective to stabilize the vital signs and reduce the analgesic medication use.

DOI： 10.1272/jnms.JNMS.2021_88-507

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: The incidence and risk factors of postoperative nausea and vomiting (PONV) and early PONV (ePONV) was evaluated in patients who underwent breast surgery with volatile anesthesia. METHODS: In this retrospective study, we used a multivariate logistic regression to investigate the incidence and risk factors of PONV. RESULTS: Among 928 patients, 166 (18%) and 220 (24%) had ePONV and PONV, respectively. In the multivariate analysis, the anesthesia duration and the use of desflurane were independent risk factors for ePONV. For PONV, the anesthesia duration and Apfel score were the independent risk factors. CONCLUSIONS: Although many previous studies have shown that PONV is a multifactorial event, our results indicate that desflurane use can be considered a main cause of ePONV. However, in the delayed phase, a higher Apfel score was the main predictor. In the early and delayed phases, a long duration of anesthesia was related to a high risk of PONV. Accordingly, avoiding a long duration of anesthesia and desflurane use is recommended for patients at a high risk of developing PONV, particularly for those with high Apfel scores.

DOI： 10.1272/jnms.JNMS.2021_88-510

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記述言語：英語  

DOI： 10.1016/S0140-6736(20)30488-8

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE: Remimazolam, an ultra-short-acting benzodiazepine sedative is equally effective as propofol in induction and maintenance of general anesthesia with improved hemodynamic stability in American Society of Anesthesiologists (ASA) Class I and II patients. This trial investigated remimazolam's efficacy and safety in vulnerable patients (ASA Class III) undergoing elective general surgery. METHODS: A multicenter, randomized, double-blind, parallel-group trial in 67 adult surgical patients undergoing general anesthesia with two remimazolam induction doses (6 mg kg-1 h-1-group A and 12 mg kg-1 h-1-group B) has been conducted in 6 trials sites in Japan. Remimazolam was infused up to 2 mg kg-1 h-1 for maintenance of anesthesia in both groups. RESULTS: The functional anesthetic capability of the investigated drug was 100% in both arms. The mean time to loss of consciousness (LoC) was significantly shorter in group B (81.7 s) compared to group A (97.2 s), p = 0.0139. The mean bispectral index (BIS) value during maintenance of anesthesia ranged from 46.0 to 68.0 and from 44.7 to 67.5 in group A and B, respectively. There was no statistically significant difference between the remimazolam arms concerning the incidence of blood pressure (BP) decrease (67.7% in group B vs. 54.8% in group A), recovery profile or the incidence or severity of adverse events (AEs) or adverse drug reactions (ADRs). CONCLUSION: Both induction regimens (6 and 12 mg kg-1 h-1) were equally efficacious and safe in surgical patients ASA Class III. A significantly shorter time to LoC was observed with the higher remimazolam dosage. Clinical trial registration This trial is registered with the Japan Pharmaceutical Information Center-Clinical Trials Information (JapicCTI). JapicCTI number: 121977.

DOI： 10.1007/s00540-020-02776-w

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE: This trial was conducted to confirm the non-inferiority of remimazolam versus propofol in the induction and maintenance of general anesthesia in surgical patients. METHODS: Surgical patients (n = 375) were randomized to remimazolam started at 6 or 12 mg/kg/h by continuous intravenous (IV) infusion until the loss of consciousness (LoC), followed by 1 mg/kg/h to be adjusted as appropriate until the end of surgery or IV propofol administered as a slow bolus of 2.0-2.5 mg/kg until LoC followed by 4-10 mg/kg/h until the end of surgery. Efficacy was measured via the combined primary endpoint of no intraoperative awakening/recall, no need for rescue sedatives, and no body movements. Adverse events and adverse drug reactions (ADRs) were monitored for safety. RESULTS: Efficacy rates were 100% in all treatment groups, and the non-inferiority of remimazolam was demonstrated [95% confidence interval (- 0.0487; 0.0250)]. The time to LoC was longer in the remimazolam 6 (p < 0.0001) and 12 mg/kg/h (p = 0.0149) groups versus propofol. The time to extubation was longer in both remimazolam groups versus the propofol group (p ≤ 0.0001). The incidence of ADRs was similar in the remimazolam groups (39.3% and 42.7%, respectively) compared with the propofol group (61.3%). Decreased blood pressure occurred in 20.0% and 24.0% of patients treated with 6 and 12 mg/kg/h remimazolam, respectively, compared with 49.3% of patients receiving propofol. Injection site pain was reported in 18.7% of propofol patients but not in those receiving remimazolam. CONCLUSIONS: This trial demonstrated that remimazolam was well tolerated and non-inferior to propofol with regard to efficacy as a sedative hypnotics for general anesthesia. CLINICAL TRIAL REGISTRATION: This trial is registered with the Japan Pharmaceutical Information Center - Clinical Trials Information (JapicCTI). JapicCTI number: 121973.

DOI： 10.1007/s00540-020-02788-6

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The Sensmart Model X-100 (Nonin Medical Inc, Plymouth, MN, USA) is a relatively new device that possesses two sets of emitters and detectors and uses near infrared spectroscopy (NIRS) to measure regional cerebral oxygen saturation (rSO2). The value of rSO2 obtained by other NIRS devices is affected by physiological and anatomical variables such as hemoglobin concentration, area of cerebrospinal fluid (CSF) layer and skull thickness. The effects of these variables have not yet been determined in measurement of rSO2 by Sensmart Model X-100. We examined the effects of area of CSF, hemoglobin concentration, and skull thickness on the values of rSO2 measured by Sensmart Model X-100 and tissue oxygen index (TOI) measured by NIRO-200NX (Hamamatsu Photonix, Hamamatsu, Japan). Forty neurosurgical, cardiac and vascular surgical patients who underwent preoperative computed tomographic (CT) scan of the brain were enrolled in this study. Regional cerebral oxygen saturation (rSO2) at the forehead was measured sequentially by NIRO-200NX and by Sensmart Model X-100. Simultaneously, mean arterial pressure, hemoglobin concentration, and partial pressure of carbon dioxide in arterial blood (PaCO2) were measured. To evaluate the effects of anatomical factors on rSO2, we measured skull thickness and area of CSF layer using CT images of the brain. Multiple regression analysis was used to examine the relationships between the rSO2 values and anatomical and physiological factors. The area of the CSF layer and hemoglobin concentration had significant associations with rSO2 measured by the Sensmart Model X-100, whereas none of the studied variables was significantly associated with TOI. The measurement of rSO2 by Sensmart Model X-100 is not affected by the skull thickness of patients. Area of the CSF layer and hemoglobin concentration may be the main biases in measurement of rSO2 by Sensmart Model X-100.

DOI： 10.1007/s10877-020-00567-y

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background:
Post hoc analysis was used to investigate the effects of renal function on the efficacy and safety of landiolol using data from the J-Land II study, which evaluated landiolol in patients with hemodynamically unstable ventricular tachycardia (VT) or ventricular fibrillation (VF) who were refractory to Class III antiarrhythmic drugs.
Methods and Results:
Patient data from the J-Land II study (n=29) were stratified by renal function (estimated glomerular filtration rate [eGFR] <45 and ≥45 mL/min/1.73 m2) and analyzed. Continuous landiolol infusion (1 μg/kg/min, i.v.) was initiated after VT/VF was suppressed with electrical defibrillation; subsequent dose adjustments were made (1-40 μg/kg/min). The primary efficacy endpoint was the proportion of patients free from recurrent VT/VF during the assessment period. Safety endpoints were also assessed. In the eGFR <45 and ≥45 mL/min/1.73 m2 groups, the median doses of landiolol during the assessment period were 9.44 and 8.97 μg/kg/min, the proportions of patients free from recurrent VT/VF were 69.2% and 81.8%, and adverse events occurred in 9 and 10 of 13 patients in each group, respectively. There were no apparent differences in the efficacy or safety of landiolol between the 2 groups.
Conclusions:
The data suggest that renal function may not affect the efficacy and safety of landiolol for hemodynamically unstable VT or VF.

DOI： 10.1253/circrep.CR-20-0017

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Most children with trisomy 13 display central apnea, and are prone to opioid-induced respiratory depression. We conducted opioid-free anesthesia for a patient with trisomy 13 and obstructive sleep apnea, and safely extubated the patient in the operating room. CASE PRESENTATION: A 27-month-old girl with trisomy 13 underwent tonsillectomy. Given her high sensitivity to opioids, general anesthesia was introduced and maintained only with 2-5% sevoflurane and 33% nitrous oxide in oxygen. We used acetaminophen for postoperative analgesia. The tracheal tube was removed under stable breathing pattern 10 min after the surgery in the operating room. Two years later, opioid-free anesthesia with 2-5% sevoflurane and 33% nitrous oxide in oxygen was again performed safely for tube insertion into both eardrums. CONCLUSION: Opioid-free anesthesia with adequate non-narcotic analgesics is safe for children with trisomy 13 with multiple apnea-related comorbidities.

DOI： 10.1186/s40981-020-00354-3

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Robot-assisted surgery and pure laparoscopic surgery are available for minimally invasive radical prostatectomy (MIRP). The differences in anesthetic management between the two MIRPs under combined general and epidural anesthesia (CGEA) remain unknown. This study therefore aimed to determine the effects of robot-assisted surgery on anesthetic and perioperative management for MIRP under CGEA. METHODS: A retrospective observational study was performed by obtaining data from the patients' electronic medical records. Demographic data, intraoperative parameters, postoperative complications, and hospital stays after the MIRPs were compared between patients who underwent robot-assisted laparoscopic radical prostatectomy (RALP) and those with pure laparoscopic radical prostatectomy (LRP). RESULTS: There were no differences in the patients' background data between the 102 who underwent RALP and 112 who underwent LRP. Anesthesia and surgical times were shorter in the RALP group than in the LRP group. Consumption of anesthetics, including intravenous opioids, and epidural ropivacaine, was less in the RALP group. Although the estimated blood loss and volume of colloid infusion were lower in the RALP group, the volume of crystalloid infusion was larger. Intraoperative allogeneic transfusion was not required in either group. There were no differences in incidents of postoperative cardiopulmonary complications or postoperative nausea and vomiting (PONV) in either MIRP group. Hospital stays after the procedure were shorter in the RALP group. CONCLUSIONS: Robot-assisted surgery required varied consumption of anesthetics and infusion management during MIRP under GCEA. It also shortened the postoperative hospital stay without increasing the rates of postoperative complications.

DOI： 10.1272/jnms.JNMS.2021_88-304

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The kidneys are prone to developing ischemia reperfusion injury (IRI) following certain renal surgeries and cardiovascular surgeries requiring cardiac arrest. Sevoflurane and ischemic preconditioning reportedly alleviate IRI, which is mediated via microRNAs. The present study compared anesthetic preconditioning (APC) and ischemic preconditioning (IPC) on microRNAs, which promote cell‑survival pathways in rats in a randomized controlled study. After undergoing right nephrectomy under general anesthesia, male Wistar rats (336±24 g) and were divided into four groups (IRI, APC, IPC and sham; n=7 each). The IRI group underwent 45 min clamping of the left renal vasculature, followed by 4 h of reperfusion. APC involved exposure to one minimum alveolar concentration sevoflurane for 15 min. IPC included three cycles of two‑min clamping and five‑min reperfusion. Blood and renal biopsy samples were assessed postoperatively to measure serum creatinine and to analyze renal microRNA (miR) expression using reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) testing and their target pathways with Ingenuity Pathway Analysis™. The present study found that serum creatinine values in APC (0.71±0.08 mg/dl) and IPC (0.73±0.1 mg/dl) groups were lower than in the IRI group (0.96±0.13 mg/dl; P<0.05), indicating amelioration of IRI by APC and IPC. RT‑qPCR followed by pathway analysis indicated that APC and IPC affect 'protein kinase B (Akt)'. APC promoted miR‑17‑3p and suppressed miR‑27a. IPC promoted miR‑19a. All the miRs were predicted to regulate phosphorylated Akt, which promotes cell‑protection. Western blot analysis showed that expression of phosphorylated Akt increased and phosphatase and tensin homologue deleted from chromosome 10 (PTEN) decreased following APC and IPC. The present study concluded that APC and IPC affect different miRs, although they are estimated to similarly promote the PTEN/phosphoinositide 3‑kinase/Akt signaling pathway, resulting in reno‑protection.

DOI： 10.3892/ijmm.2020.4477

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Intravascular lymphoma is a rare disease that progresses to multiple organ dysfunction caused primarily by tumor cell proliferation in small blood vessels. Few studies have investigated critical care management of intravascular lymphoma. We describe a rare case of multiple organ failure due to intravascular lymphoma with severe lactic acidosis in a patient who survived. A 64-year-old man with impaired consciousness was diagnosed as having intravascular large B-cell lymphoma by means of a random skin biopsy. The patient arrived at our hospital's intensive care unit (ICU) with impaired consciousness, respiratory failure that required mechanical ventilation, and lactic acidosis that required renal replacement therapy. Mechanical ventilation and renal replacement therapy were continued in the ICU, and his respiratory status and circulatory dynamics eventually stabilized. However, his impaired consciousness and hyperlactatemia did not improve until after the start of chemotherapy with doxorubicin, cyclophosphamide, vincristine, prednisolone, and rituximab. Although he developed tumor lysis syndrome immediately after chemotherapy, his systemic condition was gradually stabilized by continued critical care management primarily comprising renal replacement therapy. He was weaned from ventilator support after a tracheotomy and moved to the general ward. Hematopoietic malignancy with hyperlactatemia has a very poor prognosis; however, hyperlactatemia and impaired consciousness were dramatically improved in this patient by critical care management and chemotherapy.

DOI： 10.1272/jnms.JNMS.2019_86-606

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Respiratory depression, presenting as desaturation and bradypnea, is common during the early postoperative period. However, it has not been evaluated by appropriate monitoring. The purpose of the present study was to identify the incidence and predictors of desaturation and bradypnea following general anesthesia, using a continuous and centralized monitoring system, in non-ICU patients who did not have serious complications and did not undergo major surgery. Patients were connected to a continuous and centralized monitoring system via a pulse oximeter and respiratory rate sensor for at least 8 h after extubation. We assessed the incidence and risk factors for desaturation (SpO2 < 90% for > 10 s) and bradypnea (respiratory rate < 8 breaths/min for > 2 min) events. We retrospectively collected the clinical data of 1064 adult patients in the study. The incidences of desaturation and bradypnea were 12.1% and 5.1%, respectively. Most desaturation events occurred after the termination of oxygen administration. The greatest incidence of bradypnea was within the first hour after surgery, reducing over time. Analysis revealed that age (odds ratio [OR] 1.04, 95% confidence interval [CI] 1.03-1.06; p < 0.001), BMI (OR 1.12, 95% CI 1.06-1.18; p < 0.001) and current smoking (OR 1.91, 95% CI 1.12-3.42; p = 0.023) were significant risk factors for desaturation. Sleep apnea syndrome (OR 4.23, 95% CI 1.09-13.5; p = 0.021) and postoperative opioid administration (OR 2.76, 95% CI 1.44-5.20; p = 0.002) were significantly associated with bradypnea. Age (OR 1.04, 95% CI 1.01-1.07; p = 0.010) and postoperative opioid administration (OR 3.16, 95% CI 1.22-7.87; p = 0.019) showed a significant association with the occurrence of both desaturation and bradypnea. This study demonstrated the incidence and predictors of postoperative desaturation and bradypnea, and suggests the need for monitoring oxygen saturation and respiratory rate for at least 8 h after surgery in non-ICU patients. Use of monitoring systems might provide a safety net for postoperative patients.

DOI： 10.1007/s10877-019-00293-0

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記述言語：英語  

DOI： 10.1007/s10877-019-00358-0

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Acoustic respiratory rate (RRa) monitoring is a non-invasive method of monitoring respiratory rate in spontaneously breathing individuals. The aim of this report is to highlight the clinical utility of this monitoring system in post-thyroidectomy patients by presenting a case of respiratory compromise due to post-thyroidectomy hematoma, in which the alarm of the respiratory rate monitor alerted the nursing staff about the complication. A 61-year-old woman who uneventfully underwent right thyroid lobectomy for adenomatous goiter under general anesthesia with endotracheal intubation was being monitored postoperatively using the RRa monitoring system. The alarm of the monitor suddenly indicated tachypnea, with an increase in respiratory rate from 8 to 30 breaths/min over less than 3 min, although with normal oxygenation (SaO2 99%). Physical examination revealed the presence of a hematoma due to postoperative bleeding, which was emergently treated surgically under general anesthesia with awake videolaryngoscopy-assisted endotracheal intubation, with adequate preparations for emergency tracheostomy, if required. Videolaryngoscopy before the intubation revealed mild laryngopharyngeal edema and tracheal displacement, although awake endotracheal intubation could be easily performed with a metallic tube. Thereafter, after anesthesia induction, the hematoma was drained, hemostasis was achieved, and the wound was closed after surgical drain insertion. The patient was extubated postoperatively without any further respiratory events. The information on respiratory rate disorders provided by RRa monitoring, including the tachypnea alarm, can contribute to early detection of postoperative respiratory complications and to avoiding life-threatening situations following certain operations, such as thyroidectomy.

DOI： 10.1007/s10877-019-00283-2

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Intraoperative neuromonitoring (IONM) might reduce the incidence of injury to the recurrent laryngeal nerve (RLN) during thyroidectomy. Although dislocation of endotracheal tube surface electrodes can lead to false-positive IONM results (loss of signal), the risk factors for dislocation and the effects of muscle relaxants are unclear. Therefore, to identify factors that affect IONM results, we examined the frequency and risk factors for tube dislocation after cervical extension before surgery, the effect of sugammadex administration, and the correlation between IONM results and postoperative RLN palsy. METHODS: Thirty-nine patients scheduled for thyroidectomy from October 2016 to April 2017 were enrolled. All patients underwent standard IONM and pre- and postoperative laryngoscopy. Differences in patient characteristics in the tube dislocation group and non-dislocation group, and differences in amplitude during vagal stimulation before and after sugammadex administration, were assessed by the Mann-Whitney test or Fisher's exact test. RESULTS: Tube dislocation occurred in 27 patients (69%). Sterno-cricoid distance was significantly shorter in the dislocation group (n=27) than in the non-dislocation group (n=12) (43.88 [32.2-55.91] mm vs 49.46 [40.66-55.91] mm, respectively; p=0.048). Without sugammadex, amplitude during vagal stimulation was sufficient for monitoring. Nine patients had new-onset RLN palsy, which was transient in all patients. The sensitivity of IONM was 100%, the positive predictive value was 60%, and the negative predictive value was 100%. CONCLUSIONS: The present findings suggest that anesthesiologists should use video laryngoscopy to correct tube dislocation and that a rocuronium dose of 0.6 mg/kg, without sugammadex, is adequate for IONM.

DOI： 10.1272/jnms.JNMS.2019_86-408

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

A right aortic arch with an aberrant left subclavian artery and a Kommerell's diverticulum represents a rare anatomic variant carrying the risk of dissection or rupture. Resection of the diverticulum and re-implantation of the left subclavian artery during childhood have been recommended. Because of the risk of cerebral blood flow reduction during the aberrant subclavian artery re-implantation to the common carotid artery, monitoring and prompt measures to curb blood flow reduction are required. A 5-month-old boy was scheduled to undergo resection surgery. During the translocation of the aberrant subclavian artery to the common carotid artery, his regional oxygen saturation (rSO2) in the left cerebrum began to decrease. We increased the end-tidal CO2 (EtCO2), mean arterial pressure, and a fraction of inspired oxygen, successfully restoring the rSO2 to the initial level. No postoperative neurological complications were observed. Our experience with this patient suggests that rSO2 monitoring is a useful, and intervention protocol including hypercapnia, elevated mean arterial pressure, and hyperoxia to counter the decreased cerebral blood flow is effective in infant patients undergoing right-sided aortic arch surgery.

DOI： 10.1007/s00540-019-02700-x

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Neuropathic pain is an intractable chronic pain condition caused by damage to the somatosensory system. Although non-coding RNAs such as microRNAs are important regulators of neuropathic pain, the role of long non-coding RNAs (lncRNAs) is poorly understood. METHODS: This study used a rat model of neuropathic pain induced by lumbar fifth spinal nerve ligation (SNL). Microarray analysis of lncRNAs in the lumbar fifth dorsal root ganglion was performed at day 14 after SNL. Expression levels of H19 were examined by using quantitative PCR. In situ hybridization was used to determine the distribution of H19 at day 14 after SNL. Schwann cells were isolated from peripheral nerves at day 14 after SNL. RESULTS: H19 lncRNA was greatly increased in the L5 dorsal root ganglion at day 14 after SNL and was significantly higher at and after day 4. In the dorsal root ganglion, H19 was detected mainly in non-neuronal cells but not in primary sensory neurons. Consistent with this, H19 expression was upregulated in Schwann cells isolated from peripheral nerves after SNL. CONCLUSION: Increased H19 lncRNA in Schwann cells might be involved in neuropathic pain.

DOI： 10.1272/jnms.JNMS.2018_86-402

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記述言語：日本語   出版者・発行元：日本手術医学会  

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記述言語：日本語   出版者・発行元：日本手術医学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1253/circj.CJ-18-1361

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記述言語：日本語   出版者・発行元：日本臨床麻酔学会  

術中のデクスメデトミジン(DEX)投与が術後睡眠障害に影響するかを後方視的に検討した。脊髄くも膜下麻酔下に施行された泌尿器科手術患者を対象として、術中使用された鎮静剤によりDEX群(73例)、ミダゾラム(MDZ)群(54例)の2群に分類し、術当日の睡眠導入剤使用の有無について比較検討した。睡眠導入剤使用はDEX群5例、MDZ群13例であった。DEX群で術後の睡眠導入剤使用が有意に少なく、DEXは手術中のみの使用でも術後睡眠障害を減らす可能性が示唆された。(著者抄録)

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その他リンク： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2019&ichushi_jid=J01620&link_issn=&doc_id=20190604270007&doc_link_id=1390845713077905408&url=https%3A%2F%2Fcir.nii.ac.jp%2Fcrid%2F1390845713077905408&type=CiNii&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00003_3.gif

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Beta-blockers have been reported to improve prognosis for various cancers, but the usefulness of perioperative administration remains unclear. To assess the efficacy of perioperative administration of landiolol hydrochloride, an intravenous beta-blocker, for lung cancer, we conducted a single-center, retrospective study. This study included patients who participated in a research conducted by Nippon Medical School Hospital from August 2012 to November 2013. The main selection criteria were males and females younger than 85 years old who have undergone anatomic lung resection for lung malignancies. Fifty-seven patients, 28 in the landiolol group and 29 in the control group, were included. The postoperative relapse-free survival rate at 2 years was 0.89 (95% CI, 0.78-1.01) in the landiolol group and 0.76 (95% CI, 0.60-0.91) in the control group (Chi-squared test; P = 0.1828). The relapse-free survival rate tended to be higher in the landiolol group than in the control. Hazard ratio for relapse-free survival in the landiolol group compared to the control was 0.41 (95% CI, 0.13-1.34), demonstrating that relapse free survival was prolonged in the landiolol group (log-rank test; P = 0.1294). It was suggested that relapse-free survival was prolonged when landiolol hydrochloride was administered from the induction to completion of anesthesia. Further studies are needed to confirm our findings.

DOI： 10.1038/s41598-019-41520-7

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記述言語：英語  

DOI： 10.1186/s40981-018-0203-0

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記述言語：日本語   出版者・発行元：(一社)日本ペインクリニック学会  

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記述言語：英語  

According to the Extracorporeal Life Support Organization, the average duration of veno-venous extracorporeal membrane oxygenation (V-V ECMO) in adults with acute respiratory failure is 10.5-13.5 days. Some patients on V-V ECMO may not recover in such a short period of time, and recently, there have been more reports of prolonged V-V ECMO. However, we do not know how long it is feasible to wait for native lung recovery or lung transplant (LTx) with the use of ECMO. We describe a patient with acute exacerbation of idiopathic pulmonary fibrosis supported by ECMO for 403 days while waiting for a LTx. In this case, we kept the patient awake, and he was communicating frequently with his family. We changed the membrane oxygenator 23 times and the cannula 10 times without complication. However, we terminated the treatment on day 403 of ECMO because there was no access site for cannula insertion due to blockage by a venous thrombotic occlusion, making it impossible to continue this bridge to lung transplantation. It has become possible to maintain patients on ECMO for extended periods of time, but it is difficult to manage ECMO for more than one year without the development of a more durable lung support system.

DOI： 10.1016/j.rmcr.2018.04.015

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：CHURCHILL LIVINGSTONE  

Background & aims: We previously demonstrated that the gastric emptying rate of liquids chiefly. depended on the total amount of calories (energy content) in a uniform volume. The aim of the present study was to examine the effects of different volumes of liquids with a uniform energy content on gastric emptying.
Methods: Three types of test solutions were prepared with a uniform amount of calories (200 kcal provided by glucose) and step-wise increments in volume (200 ml, 400 ml, and 600 ml). The gastric volume of each solution was determined by ultrasound measurements of the gastric antral cross-sectional area after their ingestion by 8 healthy volunteers.
Results: The mean gastric volume decreased exponentially to nearly 0 ml 70 min after ingestion in the 200 ml group, 90 min in the 400 ml group, and 100 min in the 600 ml group. Each gastric emptying curve converged with identical slopes on the graph when the points at which the gastric emptying curves of the 200 ml and 400 ml groups reached the zero point on the Y-axis (mean gastric volume) were shifted toward 110 min on the X-axis (time scale).
Conclusions: The volume of liquid ingested with a uniform glucose-based energy content is a critical determinant of liquid gastric emptying. The gastric emptying time may be predicted following the ingestion of an isocaloric liquid with any volume over a predefined range once a gastric emptying curve following the ingestion of a liquid has been plotted on a graph. (C) 2016 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

DOI： 10.1016/j.clnu.2016.08.014

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記述言語：日本語   出版者・発行元：日本臨床麻酔学会  

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記述言語：日本語   出版者・発行元：日本臨床麻酔学会  

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記述言語：日本語   出版者・発行元：日本臨床麻酔学会  

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記述言語：日本語   出版者・発行元：日本臨床麻酔学会  

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記述言語：日本語   出版者・発行元：日本臨床麻酔学会  

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記述言語：日本語   出版者・発行元：(一社)日本ペインクリニック学会  

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記述言語：日本語   出版者・発行元：(一社)日本ペインクリニック学会  

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記述言語：日本語   出版者・発行元：(一社)日本ペインクリニック学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY  

BACKGROUND AND PURPOSE: Although oxaliplatin is an effective anti-cancer platinum compound, it can cause painful chronic neuropathy, and its molecular mechanisms are poorly understood. MicroRNAs (miRNAs) are small non-coding RNAs that negatively regulate gene expression in a sequence-specific manner. Although miRNAs have been increasingly recognized as important modulators in a variety of pain conditions, their involvement in chemotherapy-induced neuropathic pain is unknown. EXPERIMENTAL APPROACH: Oxaliplatin-induced chronic neuropathic pain was induced in rats by i.p. injections of oxaliplatin (2 mg·kg-1 ) for five consecutive days. The expression levels of miR-15b and β-site amyloid precursor protein-cleaving enzyme 1 (BACE1 also known as β-secretase 1) were examined in the dorsal root ganglion (DRG). To examine the function of miR-15b, an adeno-associated viral vector encoding miR-15b was injected into the DRG in vivo. KEY RESULTS: Among the miRNAs examined in the DRG in the late phase of oxaliplatin-induced neuropathic pain, miR-15b was most robustly increased. Our in vitro assay results determined that BACE1 was a target of miR-15b. BACE1 and miR-15b were co-expressed in putative myelinated and unmyelinated DRG neurons. Overexpression of miR-15b in DRG neurons caused mechanical allodynia in association with reduced expression of BACE1. Consistent with these results, a BACE1 inhibitor dose-dependently induced significant mechanical allodynia. CONCLUSIONS AND IMPLICATIONS: These findings suggest that miR-15b contributes to oxaliplatin-induced chronic neuropathic pain at least in part through the down-regulation of BACE1.

DOI： 10.1111/bph.13698

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記述言語：英語  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：MEDICAL ASSOC NIPPON MEDICAL SCH  

Deafferentation pain induced by subarachnoid block (SAB) is rare, but it can appear in the form of recurrent phantom lower limb pain, new acute-onset stump pain in amputees, lower limb pain in patients with tabes dorsalis, and neuropathic pain. We have previously reported that thiopental is an effective treatment for deafferentation pain induced by therapeutic SAB applied to treat neuropathic pain of central origin. Here, we report the case of an amputee who developed new stump pain in his lower limb immediately after subarachnoid tetracaine was administered prior to appendectomy. A 51-year-old man who had previously undergone right below-knee amputation for acute arterial thrombosis, and who had not previously experienced chronic phantom limb or stump pain, was scheduled for emergency open appendectomy. For anesthesia, we induced SAB with a hyperbaric tetracaine solution. No paresthesia occurred during administration. However, the patient immediately complained of severe, lightning-bolt pain in the right lower limb stump after the SAB was established. He was given intravenous pentazocine, which promptly resolved the pain. Appendectomy was then performed under sedation using intravenous midazolam. The patient did not experience further deafferentation pain during his hospital stay and has reported no stump pain since discharge from the hospital. This case report suggests that SAB induces deafferentation pain in some patients and that this unusual pain can be treated with pentazocine.

DOI： 10.1272/jnms.84.183

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記述言語：英語   出版者・発行元：Springer Berlin Heidelberg  

Background: Surgery cancellation results in unavailability of the operating room and loss time. We identified the frequency of and reasons for operation cancellations after patients entered the operating room and assessed the preventability of such cancellations. Findings: A retrospective chart review of all scheduled surgical procedures proposed under general anesthesia in a period spanning 2008 to 2016 was performed, and the reasons for cancellation were assessed. A total of 30 surgery procedures were cancelled after the patient had entered the operation room and preparation for general anesthesia had been completed. Ten of 18 cases (55.6%) that were cancelled before general anesthesia induction could have been prevented, accounting for 36.7% of the overall cancellations. The majority of the cancellations after anesthesia were due to the patients’ health status. Conclusions: Improving the systems for checking patients’ medical problems and performing preoperative evaluations can reduce the number of cancellations after the patient has entered the operating room.

DOI： 10.1186/s40981-016-0066-1

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCIENCE INC  

A 69-year-old woman undergoing treatment for hypertension and epilepsy was scheduled to undergo cataract surgery. All preoperative examination results were within normal limits. Despite being tense, she walked to the operating room. Approximately 2 minutes after an intravenous line was established by an anesthesia resident, severe hypoxia and bradycardia developed, and she lost consciousness. Cardiopulmonary resuscitation was initiated immediately, and after 1 minute, she regained consciousness, and her breathing and circulation recovered. After admission to the intensive care unit, emergency coronary angiography was performed. The blood flow in all the coronary arteries was normal. However, a decrease in the apical left ventricular wall motion and an increase in the basal wall motion were observed. Based on these findings, Takotsubo cardiomyopathy was diagnosed. The wall motion gradually improved and the patient was discharged from the hospital on postoperative day 15. The respiratory depression and bradycardia were thought to be due to an inadvertent bolus of remifentanil. We surmised that the patient had received a slight amount of retained medication when the anesthesia resident established the intravenous line, which caused severe respiratory depression. It is important to note that adverse effects such as severe respiratory depression and bradycardia can be caused by even small doses of remifentanil.

DOI： 10.1016/j.jclinane.2016.08.007

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記述言語：日本語   出版者・発行元：日本臨床麻酔学会  

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記述言語：日本語   出版者・発行元：日本臨床麻酔学会  

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記述言語：日本語   出版者・発行元：日本臨床麻酔学会  

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記述言語：日本語   出版者・発行元：日本臨床麻酔学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER IRELAND LTD  

The inhalation anesthetic sevoflurane suppresses Per2 expression in the suprachiasmatic nucleus (SCN) in rodents. Here, we investigated the intra-SCN regional specificity, time-dependency, and pharmacological basis of sevoflurane-effects. Bioluminescence image was taken from the SCN explants of mPer2 promoter-destabilized luciferase transgenic rats, and each small regions of interest (ROI) of the image was analyzed. Sevoflurane suppressed bioluminescence in all ROIs, suggesting that all regions in the SCN are sensitive to sevoflurane. Clear time-dependency in sevoflurane effects were also observed; application during the trough phase of the bioluminescence cycle suppressed the subsequent increase in bioluminescence and resulted in a phase delay of the cycle; sevoflurane applied during the middle of the ascending phase induced a phase advance; sevoflurane on the descending phase showed no effect. These results indicate that the sevoflurane effect may depend on the intrinsic state of circadian machinery. Finally, we examined the involvement of GABAergic signal transduction in the sevoflurane effect. Co-application of both GABA(A) and GABA(B) receptor antagonists completely blocked the effect of sevoflurane on the bioluminescence rhythm, suggesting that sevoflurane inhibits Per2 expression via GABAergic signal transduction. Current study elucidated the anesthetic effects on the molecular mechanisms of circadian rhythm. (C) 2015 Elsevier Ireland Ltd and Japan Neuroscience Society. All rights reserved.

DOI： 10.1016/j.neures.2015.11.010

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記述言語：日本語   出版者・発行元：(一社)日本ペインクリニック学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER IRELAND LTD  

General anesthesia affects the expression of clock genes in various organs. Expression of Per2, a core component of the circadian clock, is markedly and reversibly suppressed by sevoflurane in the suprachiasmatic nucleus (SCN), and is considered to be a biochemical marker of anesthetic effect in the brain. The SCN contains various types of neurons, and this complexity makes it difficult to investigate the molecular mechanisms of anesthesia. Here, we established an in vitro experimental system using a cell line to investigate the mechanisms underlying anesthetic action. Development of the system comprised two steps: first, we developed a system for application of inhalational anesthetics and incubation; next, we established cultures of anesthetic-responsive cells expressing mPer2 promoter-dLuc. GT1-7 cells, derived from the mouse hypothalamus, responded to sevoflurane by reversibly decreasing mPer2-promoter-driven bioluminescence. Interestingly, the suppression of bioluminescence was found only in the serum-starved GT1-7 cells, which showed neuron-like morphology, but not in growing cells, suggesting that neuron-like characteristics are required for anesthetic effects in GT1-7 cells. (C) 2016 Elsevier Ireland Ltd. All rights reserved.

DOI： 10.1016/j.neulet.2016.04.005

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：IMPACT JOURNALS LLC  

The majority of ovarian cancer patients relapse after surgical resection. Evidence is accumulating regarding the role of surgery in disseminating cancer cells; in particular anaesthesia may have an impact on cancer re-occurrence. Here, we have investigated the metastatic potential of volatile anaesthetics isoflurane, sevoflurane and desflurane on ovarian cancer cells.
Human ovarian carcinoma cells (SKOV3) were exposed to isoflurane (2%), sevoflurane (3.6%) or desflurane (10.3%) for 2 hours. Metastatic related gene expression profiles were measured using the Tumour Metastasis PCR Array and qRT-PCR. Subsequently vascular endothelial growth factor A (VEGF-A), matrix metalloproteinase 11 (MMP11), transforming growth factor beta-1 (TGF-beta 1) and chemokine (C-X-C motif) receptor 2 (CXCR2) proteins expression were determined using immunofluorescent staining. The migratory capacities of SK-OV3 cells were assessed with a scratch assay and the potential role of CXCR2 in mediating the effects of volatile anaesthetics on cancer cell biology were further investigated with CXCR2 knockdown by siRNA.
All three volatile anaesthetics altered expression of 70 out of 81 metastasic related genes with significant increases in VEGF-A, MMP-11, CXCR2 and TGF-beta genes and protein expression with a magnitude order of desflurane (greatest), sevoflurane and isoflurane. Scratch analysis revealed that exposure to these anesthetics increased migration, which was abolished by CXCR2 knockdown.
Volatile anaesthetics at clinically relevant concentrations have strong effects on cancer cell biology which in turn could enhance ovarian cancer metastatic potential. This work raises the urgency for further in vivo studies and clinical trials before any conclusions can be made in term of the alteration of clinical practice.

DOI： 10.18632/oncotarget.8304

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：MEDICAL ASSOC NIPPON MEDICAL SCH  

AIM: Opioids are increasingly used to control postoperative pain via intravenous patient-controlled analgesia, with several advantages. The present study evaluated the effects of intravenous patient-controlled analgesia with different doses of fentanyl on postoperative pain and on the quality of physical/emotional recovery from surgery and anesthesia. METHODS: We retrospectively reviewed data from 288 patients, and evaluated whether intravenous patient-controlled analgesia with fentanyl correlated with the degree of postoperative pain. We then prospectively studied 47 patients who underwent elective laparoscopic cholecystectomy. The patients were randomized into 2 groups (15 or 30 μg/mL of fentanyl), and postoperative pain control was compared using a visual analog scale score. Furthermore, the Japanese 40-item quality of recovery (QoR-40J) score (global and dimensional) and Hospital Anxiety and Depression Scale (HADS) were used to assess the quality of recovery from surgery and anesthesia. RESULTS: Of 288 patients, 20% complained of intolerable pain and 18% experienced postoperative nausea and vomiting. In the prospective study, the visual analog scale pain score was lower in the Fentanyl 30 group than in the Fentanyl 15 group (p<0.05) on postoperative day 1. Dimensional QoR-40J pain subscales correlated with both the emotional state subscales (postoperative day 1, p<0.05; day 2, p<0.05) and global QoR-40 scores on both postoperative days (day 1, p<0.05; day 2, p<0.05). CONCLUSION: The postoperative pain as well as the physical and emotional quality of recovery in the patients who underwent laparoscopic cholecystectomy could be alleviated by sufficient doses of opioids.

DOI： 10.1272/jnms.83.158

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DOI： 10.1186/s40981-016-0031-z

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1186/s40981-016-0068-z

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1186/s40981-016-0028-7

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記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Kokuseido Publishing Co. Ltd  

This is a case report of a 42-year-old man who underwent suboccipital craniectomy and C-l lamino-plasty under general anesthesia. His weight and height were 32 kg and 110 cm, respectively. The patient had short limbs, a protruding forehead, a large tongue, and a short neck. Preoperative magnetic resonance imaging showed marked stenosis of the foramen magnum and cervicomedullary compression and malacia, with the smallest anteroposterior diameter of 4.5 mm. Mask ventilation and tracheal intubation were not feasible
therefore, an Airtraq® laryngoscope and a bronchial fiberscope were used. Anesthesia was maintained with propofol, remifentanil, and fentanyl. After intubation and postural change, the patient was awakened, and we confirmed the absence of any limb movement disorder. Intraoperative motor evoked potentials were normal. After extubation, he experienced numbness of the limbs. Postoperative magnetic resonance imaging revealed an enlargement of the foramen magnum and the foramen of the atlas. However, the cervicomedullary malacia remained unchanged. The cause of numbness was unknown. After rehabilitation, he became ambulatory and could walk continuously for about 300 m at a slow pace.

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記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Kokuseido Publishing Co. Ltd  

A 71-year-old male with left lung cancer was scheduled for endoscopic lung surgery under general anesthesia During a preoperative examination, the patient had hoarseness and was diagnosed with congenital laryngeal web. Differential lung ventilation was needed throughout the surgery, but the opening orifice of the laryngeal web was estimated to be too small for intubation. Therefore, we performed a tracheostomy one week before surgery, for which a double-lumen endotracheal tube was used during differential lung ventilation. Under general anesthesia the lung surgery was successfully completed, and the patient did not have any postoperative complications.

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.3892/br.2015.525

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER  

Second-line therapy has limited activity in patients with recurrent or persistent uterine cervical cancer that has progressed after chemoradiation and palliative chemotherapy. The purpose of this study was to evaluate the efficacy of negative-balance isolated pelvic perfusion (NIPP) in patients with pretreated recurrent/persistent uterine cervical cancer.Between April 2004 and May 2013, a total of 26 patients with recurrent or persistent uterine cervical cancer previously treated with platinum-based systemic chemotherapy and/or chemoradiotherapy received NIPP therapy at our institution, consisting of a 30-min isolated pelvic perfusion with cisplatin and fluorouracil, followed by isolated pelvic dialysis. Primary endpoints were response rate (RR) and progression-free survival (PFS), while secondary endpoints were overall survival (OS) and safety. Platinum pharmacokinetics were also evaluated.The RR was 57.7 % (complete response, five patients; partial response, ten patients). The median PFS and OS after NIPP therapy were 11.0 (95 % confidence interval [CI] 6.6-15.4) and 25.1 (95 % CI 17.1-33.1) months, respectively. PFS was significantly better in patients without intestinal involvement (p = 0.016) or dissemination (p < 0.001). Survival rates at 1, 2, and 3 years after initial NIPP therapy were 65.2, 50.4, and 13.4 %, respectively. The plasma pelvic-to-systemic exposure ratios were 15.4 and 15.8, based on the maximum concentration and the concentration-time curve, respectively. Most adverse events were mild (grade 1-2) (Common Terminology Criteria for Adverse Events, version 3.0). Severe neutropenia (grade 3 or higher) occurred in only 7.7 % of patients.NIPP appears to be an effective and feasible method for patients with pretreated recurrent or persistent cervical cancer.

DOI： 10.1245/s10434-015-4494-3

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記述言語：日本語   出版者・発行元：日本臨床麻酔学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier Taiwan LLC  

An increasing body of evidence shows that the choice of anesthetic can strongly influence more than simply the quality of anesthesia. Regional and general anesthesia have often been compared to ascertain whether one provides benefits through dampening the stress response or harms by accelerating cancer progression. Regional anesthesia offers considerable advantages, by suppressing cortisol and catecholamine levels and reducing muscle breakdown postoperatively. It also has less immunosuppressive effect and potentially reduces the proinflammatory cytokine response. As such, vital organ functions (e.g., brain and kidney) may be better preserved with regional anesthetics, however, further study is needed. Volatile general anesthetics appear to promote cancer malignancy in comparison to regional and intravenous general anesthetics, and reduce the body's ability to act against cancer cells by suppression of natural killer cell activity. There is not sufficient evidence to support an alteration of current clinical practice, however, further research into this area is warranted due to the potential implications elicited by current studies.

DOI： 10.1016/j.aat.2015.07.002

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記述言語：英語   掲載種別：論文集(書籍)内論文   出版者・発行元：Springer Japan  

Fluid management of neurosurgical patients has been a difficult problem for anesthesiologists. Cerebral edema may become a crisis of life. Although restrictive fluid management has been used for a long time, excessive fluid restriction may result in hypotension which can reduce cerebral perfusion pressure and cerebral blood flow. The goals of fluid management for neurosurgical patients include maintaining intravascular volume, preserving cerebral perfusion pressure, and minimizing cerebral edema. The blood-brain barrier prevents not only the movement of colloids but also small ions. Because there are so few protein molecules compared with the number of ions, the fluid movement is governed by crystalloid osmotic pressure rather than colloid oncotic pressure in the brain. Intraoperative fluid administration should be given at a rate sufficient to replace the urinary output, insensible losses, and blood loss, but a reduction of osmolality should be avoided. Fluid administration will not induce cerebral edema as long as normal serum osmolality and oncotic pressure are maintained, and cerebral hydrostatic pressures are not markedly increased.

DOI： 10.1007/978-4-431-54490-6_27

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記述言語：日本語   出版者・発行元：(一社)日本ペインクリニック学会  

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記述言語：日本語   出版者・発行元：(一社)日本ペインクリニック学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.3892/br.2015.428

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PUBLIC LIBRARY SCIENCE  

Anaesthetic preconditioning (APC) and ischemic preconditioning (IPC) ameliorate liver ischemia- reperfusion (I/R) injury and are important for regulating hepatic I/R injury. MicroRNAs (miRNAs) are short, noncoding RNA molecules of 21-23 nucleotides in length, and are currently under intensive investigation regarding their ability to regulate gene expression in a wide range of species. miRNA activity is involved in controlling a wide range of biological functions and processes. We evaluated whether APC and IPC are mediated by the same miRNAs by performing comprehensive miRNA screening experiments in a rat model of hepatic I/R injury. Twenty-one rats were randomly divided into three groups (n = 7/group): control (mock preconditioning), APC, and IPC. Control rats were subjected to 60 min of hepatic ischemia followed by 4 h of reperfusion, whereas the APC and IPC groups were preconditioned with 2% sevoflurane and hepatic ischemia for 10 min prior to ischemia-reperfusion, respectively. Liver samples were collected to measure miRNA levels after 3 h of reperfusion, and gene networks and canonical pathways were identified using Ingenuity Pathway Analysis (IPA). Blood samples were collected to measure the levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT). Although haemodynamic parameters did not vary among the groups, AST and ALT levels were significantly higher in the control group than in the APC and IPC groups. Comprehensive miRNA screening experiments revealed that most miRNAs altered in the APC group were common to those in the IPC group. IPA identified five miRNAs related to the Akt-glycogen synthase kinase-3 beta (GSK-3 beta)-cyclin D1 pathway that were significantly affected by both preconditioning strategies. The application of either APC or IPC to ameliorate hepatic I/R injury results in expression of several common miRNAs that are related to the Akt-GSK-cyclin D1 pathway.

DOI： 10.1371/journal.pone.0125866

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY-BLACKWELL  

Background and PurposeThe locus coeruleus (LC) is the principal nucleus containing the noradrenergic neurons and is a major endogenous source of pain modulation in the brain. Glial cell line-derived neurotrophic factor (GDNF), a well-established neurotrophic factor for noradrenergic neurons, is a major pain modulator in the spinal cord and primary sensory neurons. However, it is unknown whether GDNF is involved in pain modulation in the LC.
Experimental ApproachRats with chronic constriction injury (CCI) of the left sciatic nerve were used as a model of neuropathic pain. GDNF was injected into the left LC of rats with CCI for 3 consecutive days and changes in mechanical allodynia and thermal hyperalgesia were assessed. The (2)-adrenoceptor antagonist yohimbine was injected intrathecally to assess the involvement of descending inhibition in GDNF-mediated analgesia. The MEK inhibitor U0126 was used to investigate whether the ERK signalling pathway plays a role in the analgesic effects of GDNF.
Key ResultsBoth mechanical allodynia and thermal hyperalgesia were attenuated 24h after the first GDNF injection. GDNF increased the noradrenaline content in the dorsal spinal cord. The analgesic effects continued for at least 3 days after the last injection. Yohimbine abolished these effects of GDNF. The analgesic effects of GDNF were partly, but significantly, inhibited by prior injection of U0126 into the LC.
Conclusions and ImplicationsGDNF injection into the LC exerts prolonged analgesic effects on neuropathic pain in rats by enhancing descending noradrenergic inhibition.

DOI： 10.1111/bph.13073

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記述言語：英語   出版者・発行元：(一社)日本インターベンショナルラジオロジー学会  

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記述言語：英語   出版者・発行元：(公社)日本医学放射線学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：BIOMEDICAL RESEARCH PRESS LTD  

Commonly used anesthetics adversely affect the developing brain, but the mechanisms remain unknown. We previously showed that the expressions of microRNAs (miRNAs) in major organs are affected by anesthetics. Therefore, we used TaqMan low-density array (TLDA) to analyze gene expression in the hippocampus of neonatal rats exposed to sevoflurane and performed behavioral tests after they reached adulthood to evaluate cognitive and memory function. Rat male pups at postnatal day 7 were exposed to 1.9% sevoflurane for 3 h, and the hippocampus-miRNA expression profile on postnatal day 8 was determined. Open field and fear conditioning tests conducted during postnatal weeks 7 and 8 indicated that sevoflurane-exposed rats, but not controls, exhibited anxiety- like disorders. TLDA analysis identified 20 differentially expressed miRNAs, which were not shared between postnatally and maturely sevoflurane-exposed rats. The level of rno-miR-632, which targets brain-derived neurotrophic factor and calcium channel, voltage-dependent, alpha 2/delta subunit 2, increased by 10-fold, indicating that exposure to sevoflurane during early neural development alters hippocampus-miRNA expression and may induce subsequent behavioral disorders.

DOI： 10.2220/biomedres.36.347

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1186/1471-2253-14-82

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPANDIDOS PUBL LTD  

The volatile anesthetic, sevoflurane, is widely used in surgery. Over the years, there has been a growing interest in the biological effects of sevoflurane on tissue and organ systems and the molecular mechanisms involved. MicroRNAs (miRNAs or miRs) acting as pivotal post-transcriptional regulators for fine-tuning gene networks are not only expressed intracellularly, but are also secreted into the plasma. However, the sevoflurane-associated dynamics of circulating miRNAs and the effects of sevoflurane on tissues remain unknown. Thus, the aim of this study was to perform a comprehensive analysis of circulating miRNA levels and compositions in sevoflurane-anesthetized rats. The rats were allowed to breathe spontaneously under 2% sevoflurane anesthesia for 6 h, and we performed a quantitative polymerase chain reaction (PCR)-based array analysis of the time-dependent changes in plasma miRNA levels and compositions. Subsequently, we validated the levels of muscle-specific miRNAs (also known as myomiRNAs; miR-1, miR-133a, miR-133b and miR-206) of the plasma, heart and skeletal muscle by quantitative PCR following 3 and 6 h of anesthesia, as well as at 1, 3, 7 and 14 days post-anesthesia. Of the 210 miRNAs detected in the rat plasma from the control group (no anesthesia), 161 plasma miRNAs (77%) were transiently downregulated as a result of sevoflurane anesthesia. Although the downregulation of the plasma miRNAs (148 out of the 161 plasma mRNAs; 92%) recovered immediately after anesthesia, the plasma levels of 4 muscle-specific miRNAs were persistently downregulated until 14 days post-anesthesia. In the cardiac and skeletal muscles, the expression levels of the muscle-specific miRNAs were upregulated within 2 weeks post-anesthesia, indicating that the expression levels of the muscle-specific miRNAs in the cardiac and skeletal muscles and their plasma levels are substantially inversely correlated following anesthesia. Our data suggest that sevoflurane predominantly affects cardiac and skeletal muscles and suppresses the release of miRNA from these tissues into the circulation. This new information provides novel insight into the molecular mechanisms of action of the anesthetic, sevoflurane.

DOI： 10.3892/ijmm.2014.1739

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記述言語：英語  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPANDIDOS PUBL LTD  

General anesthesia is commonly used in the surgical arena, but little is known regarding its influence at the genomic and molecular levels. MicroRNAs (miRNAs) belong to a new class of non-coding RNA molecules which influence cell biology. In the present study, it was hypothesized that miRNAs alter gene expression levels under general anesthesia. The aim was to compare the miRNA expression profiles in the rat hippocampus in response to anesthesia with representative volatile (sevoflurane) and intravenous (propofol) anesthetics. Wistar Rats were randomly assigned to either a 2.4% sevoflurane, 600 mu g/kg/min propofol or control (without anesthetics) group. Total RNA from hippocampal samples which contained miRNA was subjected to quantitative reverse transcription-polymerase chain reaction and Taqman Low-Density Arrays (TLDA). A total of 373 miRNAs are associated with rats and the TLDA analysis revealed that 279 expressed miRNAs (74.8%) were expressed in all three groups. Significant differences in the levels of 33 of the 279 expressed miRNAs (11.8%) were observed among the three groups in response to the anesthetic agents, and when compared with the control group, significant differences were found in 26 of the 279 expressed miRNAs (9.3%). Following sevoflurane anesthesia, the levels of four miRNAs were significantly increased and those of 12 were significantly reduced. By contrast, following propofol anesthesia, the levels of 11 miRNAs were significantly reduced but no miRNAs exhibited significantly elevated levels. Fourteen miRNAs were significantly differentially expressed between the two anesthesia groups. In conclusion, sevoflurane and propofol exerted different effects on miRNA expression in the rat hippocampus.

DOI： 10.3892/mmr.2014.2038

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掲載種別：研究論文（学術雑誌）  

DOI： 10.1007/s12325-014-0123-y

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER  

Postoperative atrial fibrillation (POAF) is one of the most common complications after cardiac surgery. Patients who develop POAF have a prolonged stay in the intensive care unit and hospital and an increased risk of postoperative stroke. Many guidelines for the management of cardiac surgery patients, therefore, recommend perioperative administration of beta-blockers to prevent and treat POAF. Landiolol is an ultra-short acting beta-blocker, and some randomized controlled trials of landiolol administration for the prevention of POAF have been conducted in Japan. This meta-analysis evaluated the effectiveness of landiolol administration for the prevention of POAF after cardiac surgery.
The Medline/PubMed and BioMed Central databases were searched for randomized controlled trials comparing cardiac surgery patients who received perioperative landiolol with a control group (saline administration, no drug administration, or other treatment). Two independent reviewers selected the studies for inclusion. Data regarding POAF and safety outcomes were extracted. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using the Mantel-Haenszel method (fixed effects model).
Six trials with a total of 560 patients were included in the meta-analysis. Landiolol administration significantly reduced the incidence of POAF after cardiac surgery (OR 0.26, 95% CI 0.17-0.40). The effectiveness of landiolol administration was similar in three groups: all patients who underwent coronary artery bypass grafting (CABG) (OR 0.27, 95% CI 0.17-0.43), patients who underwent CABG compared with a control group who received saline or nothing (OR 0.28, 95% CI 0.17-0.45), and all patients who underwent cardiac surgery compared with a control group who received saline or nothing (OR 0.27, 95% CI 0.17-0.42). Only two adverse events associated with landiolol administration were observed (2/302, 0.7%): hypotension in one patient and asthma in one patient.
Landiolol administration reduces the incidence of POAF after cardiac surgery and is well tolerated.

DOI： 10.1007/s12325-014-0116-x

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

INTRODUCTION: Results from the multicenter trial (J-Land study) of landiolol versus digoxin in atrial fibrillation (AF) and atrial flutter (AFL) patients with left ventricular (LV) dysfunction revealed that landiolol was more effective for controlling rapid HR than digoxin. The subgroup analysis for patient characteristics was conducted to evaluate the impact on the efficacy and safety of landiolol compared with digoxin. METHODS: Two hundred patients with AF/AFL, heart rate (HR) ≥ 120 beats/min, and LV ejection fraction (LVEF) 25-50% were randomized to receive either landiolol (n = 93) or digoxin (n = 107). Successful HR control was defined as ≥20% reduction in HR together with HR < 110 beats/min at 2 h after starting intravenous administration of landiolol or digoxin. The subgroup analysis for patient characteristics was to evaluate the impact on the effectiveness of landiolol in AF/AFL patients complicated with LV dysfunction. RESULTS: The efficacy in patients with NYHA class III/NYHA class IV was 52.3%/35.3% in landiolol, and 13.8%/9.1% in digoxin (p < 0.001 and p = 0.172), lower LVEF (25-35%)/higher LVEF (35-50%) was 45.7%/51.1% in landiolol, and 14.0%/12.7% in digoxin (p < 0.001 and p < 0.001), CKD stage 1 (90 < eGFR)/CKD stage 2 (60 ≤ eGFR < 90)/CKD stage 3 (30 ≤ eGFR < 60)/CKD stage 4 (15 ≤ eGFR < 30) was 66.7%/59.1%/39.6%/66.7% in landiolol, and 0%/13.8%/17.0%/0% in digoxin (p = 0.003, p < 0.001, p = 0.015 and p = 0.040). CONCLUSIONS: This subgroup analysis indicated that landiolol was more useful, regardless of patient characteristics, as compared with digoxin in AF/AFL patients complicated with LV dysfunction. Particularly, in patients with impaired renal function, landiolol should be preferred for the purpose of acute rate control of AF/AFL tachycardia.

DOI： 10.1007/s12325-014-0111-2

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PUBLIC LIBRARY SCIENCE  

Background: We previously reported that sevoflurane anesthesia reversibly suppresses the expression of the clock gene, Period2 (Per2), in the mouse suprachiasmatic nucleus (SCN). However, the molecular mechanisms underlying this suppression remain unclear. In this study, we examined the possibility that sevoflurane suppresses Per2 expression via epigenetic modification of the Per2 promoter.
Methods: Mice were anesthetized with a gas mixture of 2.5% sevoflurane/40% oxygen at a 6 L/min flow for 1 or 4 h. After termination, brains were removed and samples of SCN tissue were derived from frozen brain sections. Chromatin immunoprecipitation (ChIP) assays using anti-acetylated-histone antibodies were performed to investigate the effects of sevoflurane on histone acetylation of the Per2 promoter. Interaction between the E'-box (a cis-element in the Per2 promoter) and CLOCK (the Clock gene product) was also assessed by a ChIP assay using an anti-CLOCK antibody. The SCN concentration of nicotinamide adenine dinucleotide (NAD(+)), a CLOCK regulator, was assessed by liquid chromatographymass spectrometry.
Results: Acetylation of histone H4 in the proximal region of the Per2 promoter was significantly reduced by sevoflurane. This change in the epigenetic profile of the Per2 gene was observed prior to suppression of Per2 expression. Simultaneously, a reduction in the CLOCK-E'-box interaction in the Per2 promoter was observed. Sevoflurane treatment did not affect the concentration of NAD(+) in the SCN.
Conclusions: Independent of NAD(+) concentration in the SCN, sevoflurane decreases CLOCK binding to the Per2 promoter E'-box motif, reducing histone acetylation and leading to suppression of Per2 expression.

DOI： 10.1371/journal.pone.0087319

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記述言語：日本語   出版者・発行元：Kokuseido Publishing Co. Ltd  

Off-pump coronary artery bypass grafting (OPCAB) has some advantages in reduction of postoperative complications including systematic inflammatory response, myocardial injury, renal injury and cerebral injury, compared to on-pump coronary artery bypass grafting. It is important to reduce myocardial oxygen consumption during anesthesia for OPCAB. The anesthesiologists should collaborate with the cardiac surgeons and plan the best perioperative strategy for rapid recovery. The anesthesiologists should pay attention to hemodynamic instability and myocardial ischemia during anastomosis. Fast-track anesthesia offers many benefits which lead to earlier ambulation, earlier discharge and earlier rehabilitation. Further fast-track anesthesia including extubation after OPCAB in the operating room is needed, but can only be performed in selected patients.

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記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Kokuseido Publishing Co. Ltd  

As a population ages, an increase in the number of patients with cardiac complications who undergo noncardiac surgeries is observed The perioperative mortality for noncardiac surgery is approximately 1-5%
approximately 20-35% of these cases are due to cardiovascular complications. Among them, perioperative myocardiac infarction/ischemia is a factor that leads to poor prognosis, and the ACC/AHA guidelines emphasize this aspect An important task of the anesthesiologist is to accurately assess risks in patients undergoing noncardiac surgeries and avoid adverse cardiovascular events.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPANDIDOS PUBL LTD  

The two most common forms of chronic pain are inflammatory pain and neuropathic pain. Nevertheless, the underlying mechanisms of these pain conditions and their therapeutic responses are poorly understood. MicroRNAs (miRNAs) negatively regulate cell genes, and thus control cell proliferation, inflammation and metabolism. In the present study, we examined gene expression in the hippocampus of rats in two models of chronic pain. In addition, we used the left hindpaw procedure to identify differences in the bilateral hippocampus. We divided the rats into the 4 following groups: the group with chronic constriction injury (CCI), the sham-operated group, the group injected with complete Freund's adjuvant (CFA) and the group injected with normal saline. miRNA expression profiles were analyzed using TaqMan low-density array (TLDA). We observed 54 miRNAs (22.7%) in the rats with CCI rats that were differentially expressed, including 7 miRNAs that were downregulated compared with the sham-operated rats. In the CFA-injected rats, 40 miRNAs (16.8%) were differentially expressed, including 8 miRNAs that were downregulated compared with the normal saline-injected rats. Pearson's correlation co-efficient for all detected miRNAs in the rat hippocampus failed to identify differences between the hippocampi bilaterally. An unsupervised cluster analysis produced separate clusters between the control and experimental groups. In this study, we demonstrate the differential expression of hippocampal miRNAs in two rat models of chronic pain; however, no significant differences were observed bilaterally in hippocampal miRNA expression. Further research is required to determine the correlation among miRNAs, messenger RNAs (mRNAs) and proteins.

DOI： 10.3892/ijmm.2013.1504

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記述言語：英語  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：MEDICAL ASSOC NIPPON MEDICAL SCH  

Background: Preoperative ingestion of only clear fluids until 2 hours before induction of anesthesia is a common preoperative fasting regimen. Gastric emptying times, however, vary among clear fluids. We therefore investigated the gastric emptying of 2 clear glucose-electrolyte drinks.
Method: A 2-way crossover study was performed in 10 healthy volunteers. After fasting, the volunteers drank 500 mL of either OS-1 (R), an oral rehydration solution, or Pocari Sweat (R), a popular sports drink, over 3 minutes in a standing position. Magnetic resonance imaging was performed before, immediately after, and 30 minutes after the drinking of each test fluid. The difference in gastric emptying between OS-1 (R) and Pocari Sweat (R) was evaluated by comparing gastric fluid volume, flow rate, and residual ratio. We also compared the flow rates of sodium, potassium, carbohydrates, and osmotically active particles in the 2 test fluids.
Results: Gastric fluid volume 30 minutes after drinking was significantly smaller for OS-1 (R) (76.0 +/- 57.0 mL) than for Pocari Sweat (R) (158.1 +/- 73.5 mL, p&lt;0.01), although the volumes did not differ before or immediately after drinking. The flow rate was significantly faster for OS-1 (R) (10.66 +/- 3.34 mL) than for Pocari Sweat (R) (8.68 +/- 3.02 mL/min, p&lt;0.05), and the residual ratio was significantly smaller for OS-1 (R) (21 +/- 14% than for Pocari Sweat (R) (41 +/- 19%, p&lt;0.01). The flow rates of sodium, potassium, and glucose differed significantly between OS-1 (R) and Pocari Sweat (R), whereas the flow rate of osmotically active particles did not.
Conclusions: Gastric emptying is significantly faster for OS-1 (R) than for Pocari Sweat (R).

DOI： 10.1272/jnms.80.342

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER JAPAN KK  

In this study, hemoglobin vesicle (HbV), a type of artificial oxygen carrier, was infused in a hemorrhagic shock model, and the findings were compared with those of red blood cell (RBC) transfusion to evaluate the effects on blood pressure and renal function. In rats maintained in hemorrhagic shock for 30 min under general anesthesia, either irradiated stored RBCs from the same strain or HbVs were used for resuscitation. Blood pressure, serum creatinine concentration, and creatinine clearance 24 h after shock were measured. At 2 and 24 h after shock, the kidneys were removed, and the heme oxygenase-1 (HO-1) mRNA level was measured. A histopathology study was performed 24 h after shock. In both the RBC and HbV group, blood pressure recovered significantly immediately after fluid resuscitation, and blood pressure 24 h after shock did not differ significantly between the two groups. Serum creatinine concentration and creatinine clearance 24 h after shock did not differ significantly between the two groups. After 24 h, there was no significant difference in HO-1 mRNA between the groups. In the renal histopathology samples taken at 24 h after shock, there were no obvious differences between the two groups. In conclusion, HbV transfusion improved blood pressure in a manner equivalent to RBC transfusion when administered during hemorrhagic shock, and no renal dysfunction was apparent after 24 h.

DOI： 10.1007/s10047-013-0712-6

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The present study was conducted to evaluate the efficacy and safety of BLM-240 (desflurane) in comparison to sevoflurane in Japanese patients. A total of 216 patients were enrolled in this randomized comparative study at 15 medical institutions. The patients received either BLM-240 with 50-70 % N2O in O2 (n = 111), BLM-240 with 30 % O2 in air (n = 55), or sevoflurane with 50-70 % N2O in O2 (n = 50). Efficacy was evaluated by an efficacy rate based on an efficacy evaluation criteria and recovery time to extubation from the discontinuation of the anesthetics. Safety was evaluated by incidence of adverse drug reactions (ADR) and other clinical indicators. The efficacy rate of BLM-240 was 98.8 % (164/166 patients), indicating that BLM-240 is effective as an anesthetic. Time from discontinuation of anesthetic delivery to extubation was 9.7 ± 0.6 min in the BLM-240/N2O group and 14.3 ± 0.9 min in the sevoflurane/N 2O group, meeting the pre-defined non-inferiority criteria of BLM-240 to sevoflurane. There was no statistically significant difference in the incidence of total ADR between the BLM-240 group (62.0 %) and sevoflurane group (48.0 %). The results indicate that BLM-240 is an effective and safe inhalation anesthetic in Japanese patients. © 2012 Japanese Society of Anesthesiologists.

DOI： 10.1007/s00540-012-1536-x

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記述言語：日本語   出版者・発行元：(一社)日本ペインクリニック学会  

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記述言語：日本語   出版者・発行元：(一社)日本ペインクリニック学会  

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記述言語：日本語   出版者・発行元：(一社)日本ペインクリニック学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY-BLACKWELL  

Objective We elaborated the rat hippocampi in order to assess for central nervous system changes following a peripheral neuropathic injury. Design, SettingSubjects We examined the gene changes in the hippocampi of chronic constriction injury (CCI) rats with TaqMan (R) low-density array analysis (TLDA) and quantitative real-time polymerase chain reaction (qRT-PCR) of miR-125b, -132, and messenger RNAs (mRNAs) of neuropeptide Y, brain-derived neural factor, N-methyl-D-aspartate glutamate 2A receptor, gamma-aminobutyric acid A a1 receptor, gamma-aminobutyric acid A b1 receptor, gamma-aminobutyric acid B b2 receptor, serotonin 1A receptor, serotonin 2A receptor, serotonin 2C receptor, and serotonin 3A receptor on days 0, 7, and 15 after surgery. Interventions None. Outcome Measures Two behavioral tests (thermal and mechanical stimulation tests) were performed three times at 5-minute intervals to assess pain thresholds. MicroRNA (miRNA) changes were examined by TLDA. mRNA changes were examined by qRT-PCR. Statistical significance was determined by TukeyKramer's method and paired t-test. Results All rats showed mechanical and thermal hypersensitivity on the ipsilateral side. Out of 373 miRNAs analyzed, 237 were expressed, and 51 changed their expressions after CCI. By TLDA, cluster analysis found obvious miRNA changes on day 7 that tended to recover by day 15. For miR-125b, the relative expression decreased to 0.70 +/- 0.30 at day 7 and recovered to 1.65 +/- 0.19 at day 15. The miR-132 relative expressions were 0.69 +/- 0.30 and 0.70 +/- 0.15, respectively. The mRNA changes followed the miRNA changes. Conclusions Our results showed that the peripheral nerve injury altered rat hippocampal miRNA.

DOI： 10.1111/pme.12066

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：MEDICAL ASSOC NIPPON MEDICAL SCH  

Background: Dexmedetomidine has shown beneficial effects in several inflammatory models, including ischemia-reperfusion injury (IRI). This study investigated whether the continuous infusion of dexmedetomidine could improve renal IRE in rats.
Methods: Rats were subjected to either a sham operation and given pentobarbital (10 mg/kg/h; n=6) or were subjected to 45 minutes of renal ischemia and anesthetized with pentobarbital (10 mg/kg/h; n=6), dexmedetomidine (10 or 20 mu g/kg/h; both n=6), or both pentobarbital (10 mg/kg/h) and dexmedetomidine (1.0 mu g/kg/h; n=6) for 6 hours of reperfusion. Blood urea nitrogen and serum creatinine were measured 6 hours after reperfusion. Gene expression mediated by inflammatory systems in the kidney was measured with the real-time reverse-transcriptase polymerase chain reaction.
Results: Treatment with 10 or 20 mu g/kg/h of dexmedetomidine reduced renal dysfunction. The increases in the messenger RNA expression of interleukin-6, intercellular adhesion molecule 1, and inducible nitric oxide synthase caused by renal IRI were suppressed. Under In rats under pentobarbital anesthesia, 1.0 mu g/kg/h of dexmedetomidine also improved renal dysfunction after renal IRI.
Conclusion: The present study demonstrates that continuous infusion of dexmedetomidine improves renal IRI. Moreover, with pentobarbital anesthesia, a dose of dexmedetomidine lower than the sedative dose also improves renal IRI. (J Nippon Med Sch 2013; 80: 131-139)

DOI： 10.1272/jnms.80.131

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background: Our previous studies revealed that application of the inhalation anesthetic, sevoflurane, reversibly repressed the expression of Per2 in the mouse suprachiasmatic nucleus (SCN). We aimed to examine whether sevoflurane directly affects the SCN. Methods: We performed in vivo and in vitro experiments to investigate rat Per2 expression under sevoflurane-treatment. The in vivo effects of sevoflurane on rPer2 expression were examined by quantitative in situ hybridization with a radioactively-labeled cRNA probe. Additionally, we examined the effect of sevoflurane anesthesia on rest/activity rhythms in the rat. In the in vitro experiments, we applied sevoflurane to SCN explant cultures from Per2-dLuc transgenic rats, and monitored luciferase bioluminescence, representing Per2 promoter activity. Bioluminescence from two peripheral organs, the kidney cortex and the anterior pituitary gland, were also analyzed. Results: Application of sevoflurane in rats significantly suppressed Per2 expression in the SCN compared with untreated animals. We observed no sevoflurane-induced phase-shift in the rest/activity rhythms. In the in vitro experiments, the intermittent application of sevoflurane repressed the increase of Per2-dLuc luminescence and led to a phase delay in the Per2-dLuc luminescence rhythm. Sevoflurane treatment did not suppress bioluminescence in the kidney cortex or the anterior pituitary gland. Conclusion: The suppression of Per2-dLuc luminescence by sevoflurane in in vitro SCN cultures isolated from peripheral inputs and other nuclei suggest a direct action of sevoflurane on the SCN itself. That sevoflurane has no such effect on peripheral organs suggests that this action might be mediated through a neuron-specific cellular mechanism or a regulation of the signal transduction between neurons. © 2013 Anzai et al.

DOI： 10.1371/journal.pone.0059454

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：BIOMED CENTRAL LTD  

Background: Landiolol hydrochloride is a new beta-adrenergic blocker with a pharmacological profile that suggests it can be administered safely to patients who have sinus tachycardia or tachyarrhythmia and who require heart rate reduction. This study aimed to investigate whether intraoperative administration of landiolol could reduce the incidence of atrial fibrillation (AF) after cardiac surgery.
Methods: Of the 200 consecutive patients whose records could be retrieved between October 2006 and September 2007, we retrospectively reviewed a total of 105 patients who met the inclusion criteria: no previous permanent/persistent AF, no permanent pacemaker, no renal insufficiency requiring dialysis, and no reactive airway disease, etc. Landiolol infusion was started after surgery had commenced, at an infusion rate of 1 mu g/kg/min, titrated upward in 3-5 mu g/kg/min increments. The patients were divided into 2 groups: those who received intraoperative beta-blocker therapy with landiolol (landiolol group) and those who did not receive any beta-blockers during surgery (control group). An unpaired t test and Fisher's exact test were used to compare between-group differences in mean values and categorical data, respectively.
Results: Seventeen of the 105 patients (16.2%) developed postoperative atrial fibrillation: 5/57 (8.8%) in the landiolol group and 12/48 (25%) in the control group. There was a significant difference between the two groups (P=0.03). The incidence of AF after valve surgery and off-pump coronary artery bypass grafting was lower in the landiolol group, although the difference between the groups was not statistically significant.
Conclusions: Our retrospective review demonstrated a marked reduction of postoperative AF in those who received landiolol intraoperatively. A prospective study of intraoperative landiolol for preventing postoperative atrial fibrillation is warranted.

DOI： 10.1186/1749-8090-8-19

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.3892/ijmm.2012.1163

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記述言語：英語  

DOI： 10.1253/circj.CJ-12-1618

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1097/EJA.0b013e328356fba5

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

Background: In previous studies, the authors showed that anesthetics affect the expression ratios of many genes in rat liver. microRNAs (miRNA) negatively regulate more than 30% of genes in cells, and control cell proliferation, inflammation, and metabolism. The authors hypothesized that anesthetics influence miRNA expression in the liver, and performed miRNA screening tests using TaqMan low-density arrays.
Methods: Rats were randomly assigned to the 2.4% sevoflurane group, the 600 mu g.kg(-1).min(-1) propofol group, and the control group without anesthetics. Rats were allowed to breathe spontaneously under anesthesia for 6 h. The miRNA expression profile of the liver was analyzed, and 15 representative miRNAs were validated by quantitative real-time reverse transcriptase polymerase chain reaction.
Results: TaqMan low-density arrays analysis showed 46 miRNAs that were differentially expressed by anesthetics. After sevoflurane treatment, 16 miRNAs were significantly increased and 11 were significantly decreased compared with controls, whereas after propofol treatment, 31 miRNAs were increased and 8 were decreased. Twenty expressed miRNAs were common to both anesthetics, whereas three miRNAs were differentially expressed. Bland-Altman analysis was performed across the validations to compare the fold changes measured by both methods, and they were equivalent (mean difference = 0.01, 95% CI = -0.26 to 0.27). This showed that the TaqMan low-density arrays results are accurate and can be confirmed using an independent experimental approach.
Conclusion: The results showed that anesthetics cause many miRNA expression changes, and the miRNA expression pattern was particular for each anesthetic. Further studies are needed to determine the functional consequence of miRNA modulation by anesthetics.

DOI： 10.1097/ALN.0b013e3182746676

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

A 55-year-old man was transferred to our hospital with spontaneous esophageal rupture. An emergency operation of mediastinum drainage by thoracotomy was performed. On postoperative day 8, he had new abcesses located at the upper mediastinum around the esophagus, and required another operation. But one-lung ventilation for the operation was difficult, because of profound hypoxia caused by the acute respiratory distress syndrome (ARDS) with severe sepsis. Therefore we introduced V-V ECMO for the treatment of severe hypoxia and could anesthetize him safely during surgical operation. Intraoperative and post-operative hemodynamics was stable. His respiratory condition improved, and he was weaned from V-V ECMO. Unfortunately, postoperative day 11, he died because of sudden intrathoracic bleeding from the thoracic aorta which might have been infected by the severe mediastinitis.

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記述言語：日本語   出版者・発行元：日本臨床麻酔学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER IRELAND LTD  

Some anesthetics can affect gene expression. Previously, we reported that sevoflurane anesthesia drastically and reversibly repressed the expression of mouse Per2 (mPer2), a core clock gene in the suprachiasmatic nucleus (SCN). In the current study, we examined the time-dependent effect of sevoflurane on mPer2 expression and its interactions with the circadian rest/activity rhythm of mice. During certain hours of the day, mice were anesthetized with 2.5% sevoflurane in 40% oxygen for 4 h. The expression level of mPer2 in the SCN was measured by in situ hybridization using a radiolabeled cRNA probe. Anesthesia during the morning hours showed the greatest repressive effect on mPer2 expression. Sevoflurane anesthesia repressed mPer2 expression during the conditions of light/dark and constant dark, and the light conditions modified the repression rate under anesthesia. Moreover, anesthesia in the morning also repressed mPer2 expression the following day. This dominant effect of anesthesia in the morning indicates that sevoflurane anesthesia affects the onset of mPer2 transcription. Behavior analysis revealed that the anesthetic treatment also induced a phase-delay in the rest/activity rhythm. However, no time-dependent effects of anesthesia on the circadian rest/activity rhythm were observed. Further investigation into the molecular events caused by anesthesia are required to explain atypical clinical signs observed in patients after surgical procedures, such as fatigue, sleep disorder, mood alteration and delirium. (c) 2012 Elsevier Ireland Ltd. All rights reserved.

DOI： 10.1016/j.neulet.2012.07.061

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：DOVE MEDICAL PRESS LTD  

Background: The efficacy of sivelestat in the treatment of acute lung injury/acute respiratory distress syndrome (ALI/ARDS) has not been established. In part, this is due to the wide variety of factors involved in the etiology of ALI/ARDS. In this study, we examined the efficacy of sivelestat in patients with ALI/ARDS associated with abdominal sepsis.
Methods: The subjects were 49 patients with ALI/ARDS after surgery for abdominal sepsis. The efficacy of sivelestat was retrospectively assessed in two treatment groups, ie, a sivelestat group (n = 34) and a non-sivelestat group (n = 15).
Results: The sivelestat group showed significant improvements in oxygenation, thrombocytopenia, and multiple organ dysfunction score. The number of ventilator days (6.6 +/- 6.1 versus 11.1 +/- 8.4 days; P = 0.034) and length of stay in the intensive care unit (8.5 +/- 6.2 versus 13.3 +/- 9.5 days; P = 0.036) were significantly lower in the sivelestat group. The hospital mortality rate decreased by half in the sivelestat group, but was not significantly different between the two groups.
Conclusion: Administration of sivelestat to patients with ALI/ARDS following surgery for abdominal sepsis resulted in early improvements of oxygenation and multiple organ dysfunction score, early ventilator weaning, and early discharge from the intensive care unit.

DOI： 10.2147/DDDT.S36436

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.2220/biomedres.33.255

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：BIOMED CENTRAL LTD  

Background: Although general anesthesia is widely used in the surgical arena, the mechanisms by which general anesthetics act remain unclear. We previously described alterations in gene expression ratios in hepatic tissue taken from rats treated with anesthetics. Consequently, it is considered that anesthetics influence liver metabolism. Thus, the goal of this study was to use pattern recognition analysis of proton nuclear magnetic resonance spectra to visualize changes in liver metabolic phenotypes in response to widely used intravenous anesthetics (propofol and dexmedetomidine) and inhalational anesthetics (sevoflurane and isoflurane).
Methods: Rats were randomized into 13 groups (n = 6 in each group), and each group received one of following agents: propofol, dexmedetomidine, sevoflurane, isoflurane, or no anesthetic (control group). The liver was directly removed from rats immediately after or 24 h or 48 h after a 6-h period of anesthesia. Hydrophilic compounds were extracted from the liver and were analyzed with proton nuclear magnetic resonance spectroscopy. All spectral data were processed and analyzed by principal component analysis for comparison of metabolite profiles.
Results: Data were visualized by plotting principal component (PC) scores. In the plots, each point represents an individual sample. Each group was clustered separately on the plots, and the PC scores of the propofol group were clearly distinct from those of the control group and other anesthetic groups. The difference in PC scores was more pronounced immediately after completion of anesthesia when compared with 24 or 48 h after completion of anesthesia. Although the effect of intravenous anesthetics on the liver dissipated over time, the effect of inhalational anesthetics persisted.
Conclusions: Propofol, dexmedetomidine, sevoflurane and isoflurane exert different effects on liver metabolism. In particular, liver metabolism was markedly altered after exposure to propofol. The effect of anesthesia on the liver under propofol or dexmedetomidine resolved rapidly when compared with the effect under sevoflurane or isoflurane.

DOI： 10.1186/1471-2342-12-28

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その他リンク： https://dblp.uni-trier.de/db/journals/bmcmi/bmcmi12.html#TajimaHKS12

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY-BLACKWELL  

BACKGROUND AND PURPOSE The locus coeruleus (LC) is a major source of noradrenergic projections to the dorsal spinal cord, and thereby plays an important role in the modulation of nociceptive information. The LC receives inputs from substance P (SP)-containing fibres from other regions, and expresses the NK1 tachykinin receptor, a functional receptor for SP. In the present study, we investigated the roles of SP in the LC in neuropathic pain. EXPERIMENTAL APPROACH Chronic constriction injury (CCI) of the left sciatic nerve was performed in rats to induce neuropathic pain. After development of neuropathic pain, SP was injected into the LC and the nocifensive behaviours were assessed. The involvement of noradrenergic descending inhibition in SP-induced analgesia was examined by i.t. administration of yohimbine, an a2-adrenoceptor antagonist. NK1 receptor expression in the LC was examined by immunohistochemistry. KEY RESULTS In CCI rats, mechanical allodynia was alleviated by SP injection into the LC. These effects were abolished by prior injection of WIN 51708, an NK1 receptor antagonist, into the LC or i.t. treatment with yohimbine. NK1 receptor-like immunoreactivity was observed in noradrenergic neurons throughout the LC in intact rats, and remained unchanged after CCI. CONCLUSION AND IMPLICATIONS SP in the LC exerted analgesic effects on neuropathic pain through NK1 receptor activation and resulted in facilitation of spinal noradrenergic transmission. Accordingly, manipulation of the SP/NK1 receptor signalling pathway in the LC may be a promising strategy for effective treatment of neuropathic pain.

DOI： 10.1111/j.1476-5381.2011.01820.x

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記述言語：日本語   出版者・発行元：(一社)日本ペインクリニック学会  

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記述言語：日本語   出版者・発行元：(一社)日本ペインクリニック学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：BIOMED CENTRAL LTD  

Background: Acute hypoxemic respiratory failure (AHRF) is one of the most serious complications after cardiovascular surgery. It remains unclear whether noninvasive ventilation (NIV) has potential as an effective therapy for AHRF after cardiovascular surgery, although many reports have described the use of NIV for AHRF after extubation. The aim of this study was to investigate the effectiveness of NIV in the early stage of mild AHRF after cardiovascular surgery.
Methods: We retrospectively analyzed all patients admitted to the intensive care unit after cardiovascular surgery, whose oxygenation transfer (PaO2/FIO2) deteriorated mildly after extubation, and in whom NIV was initiated. A two-way analysis of variance and the Bonferroni multiple comparisons procedure, the Mann-Whitney test, Fisher's exact test or the chi(2) test was performed.
Results: A total of 94 patients with AHRF received NIV, of whom 89 patients (94%) successfully avoided endotracheal intubation (successful group) and five patients required reintubation (reintubation group). All patients, including the reintubated patients, were successfully weaned from mechanical ventilation and discharged from the intensive care unit. In the successful group, PaO2/FIO2 improved and the respiratory rate decreased significantly within 1 h after the start of NIV, and the improvement in PaO2/FIO2 remained during the whole NIV period.
Conclusion: We conclude that NIV is beneficial for mild AHRF after cardiovascular surgery when it is started within 3 h after mild deterioration of PaO2/FIO2. We also think that it is important not to hesitate before performing reintubation when NIV is judged to be ineffective.

DOI： 10.1186/1749-8090-7-41

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1253/circj.CJ-11-1332

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

We experienced anesthesia for total arch and descending aorta replacement and aortic valve replacement for post-repair aneurysm of coarctation of aorta and aortic stenosis. Because there was possibility that post coarctectomy syndrome would occur after repair of coarctation of aorta, administration of depressor that acts on renin-angiotensin-aldosterone and careful observation were needed postoperatively. In consideration of the development of collateral vessels, preoperative imaging evaluation was added and operative method in cardiopulmonary bypass was adjusted. Careful preoperative evaluation is very important in cardiac anesthesia.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER TOKYO  

In many countries, patients are generally allowed to have clear fluids until 2-3 h before surgery. In Japan, long preoperative fasting is still common practice. To shorten the preoperative fasting period in Japan, we tested the safety and efficacy of oral rehydration therapy until 2 h before surgery.
Three hundred low-risk patients scheduled for morning surgery in six university-affiliated hospitals were randomly assigned to an oral rehydration solution (ORS) group or to a fasting group. Patients in the ORS group consumed up to 1,000 ml of ORS containing balanced glucose and electrolytes: 500 ml between 2100 the night before surgery and the time they woke up the next morning and 500 ml during the morning of surgery until 2 h before surgery. Patients in the fasting group started fasting at 2100 the night before surgery. Primary endpoints were gastric fluid volume and pH immediately after anesthesia induction. Several physiological measures of hydration and electrolytes including the fractional excretion of sodium (FENa) and the fractional excretion of urea nitrogen (FEUN) were also evaluated.
Mean (SD) gastric fluid volume immediately after anesthesia induction was 15.1 (14.0) ml in the ORS group and 17.5 (23.2) ml in the fasting group (P = 0.30). The mean difference between the ORS group and fasting group was -2.5 ml. The 95% confidence interval ranged from -7.1 to +2.2 ml and did not include the noninferior limit of +8 ml. Mean (SD) gastric fluid pH was 2.1 (1.9) in the ORS group and 2.2 (2.0) in the fasting group (P = 0.59). In the ORS group, mean FENa and FEUN immediately after anesthesia induction were both significantly greater than those in the fasting group (P &lt; 0.001 for both variables). The ORS group reported they had been less thirsty and hungry before surgery (P &lt; 0.001, 0.01).
Oral rehydration therapy until 2 h before surgery is safe and feasible in the low-risk Japanese surgical population. Physicians are encouraged to use this practice to maintain the amount of water in the body and electrolytes and to improve the patient's comfort.

DOI： 10.1007/s00540-011-1261-x

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background: Our previous microarray study showed that sevoflurane anesthesia affects the expression of rat genes in multiple organs including the liver. In this study, we investigated whether liver protein expression was altered after propofol, sevoflurane, or isoflurane anesthesia. We also investigated differences in the time course of each drug 24 and 72 h after anesthesia. Methods: Rats were randomly assigned to four groups (non-anesthetized group and three groups anesthetized at each time point, n = 6 per group). A venous catheter was inserted into the caudal vein of all rats. Rats were anesthetized with each agent for 6 h, and the liver was obtained immediately after anesthesia. Proteomic analysis was performed. Results: About 4200 spots in each gel were discriminated, and at least 2619 spots were matched. Using LC-MS/MS, we identified 47 spots for propofol, 45 spots for sevoflurane, and 21 spots for isoflurane that were differentially expressed (p &lt
0.05) 0 h after anesthesia. The numbers of altered proteins were 14 and 19 in the isoflurane and sevoflurane groups, respectively, 72 h after anesthesia, but alterations in 40 proteins were seen in the propofol group 72 h after anesthesia. Conclusion: Volatile and intravenous anesthetics affected protein expression in the liver. Alterations were different for each drug, with isoflurane showing fewer altered proteins 0 h after anesthesia than the other two drugs. The time courses of those proteins were also different between individual anesthetics, suggesting fewer alterations in rat liver protein expression with volatile anesthetics than with propofol. © Watanabe et al.

DOI： 10.2174/1875039701205010008

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記述言語：日本語   出版者・発行元：(一社)日本心臓血管麻酔学会  

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記述言語：日本語   出版者・発行元：日本臨床麻酔学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.neures.2011.01.003

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：BIOMEDICAL RESEARCH PRESS LTD  

Some reports have shown that electroconvulsive shock therapy is effective for treating refractory neuropathic pain. However, its mechanism of action remains unknown. This study analyzes changes in protein expression in the brainstems of neuropathic pain model rats with or without electroconvulsive stimulation (ECS). A neuropathic pain model rat is produced by chronic constrictive injury (CCI) of the sciatic nerve. An ECS was administered to rodents once daily for 6 days after the CCI operation. After ECS, the latency to withdrawal from thermal stimulation was significantly increased. The expression of several proteins was changed after CCI. Ten proteins that increased after CCI then had decreased expression levels (close to control) after ECS, and 8 proteins that decreased after CCI then had increased expression levels (close to control) after ECS. In conclusion, ECS improved thermal hypersensitivity in a rat CCI model. Proteomic analysis showed that altered expression levels of proteins in the brainstem of CCI model rats returned to close to control levels after ECS, including many proteins associated with pain. This trend suggests an association of ECS with improved hypersensitivity, and these results may help elucidate the mechanism of this effect.

DOI： 10.2220/biomedres.32.91

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER IRELAND LTD  

Sevoflurane is an anesthetic for the general anesthesia. In this study, we showed that sevoflurane anesthesia affects the expression of mouse Per2 (mPer2), which is a clock gene in the brain which is considered the organ where the anesthetics act in. 64.5% of mPer2 circadian expression was repressed under anesthesia in the suprachiasmatic nucleus (SCN) of the brain. After recovering from the anesthesia, the repressed mPer2 expression was restored to the same level as in non anesthesia-treated mice. This repression pattern was also observed in the subsequent phases of diurnal mPer2 expression. However, obvious phase-shift in the mPer2 expression was not showed in this study. On the other hand, the behavior analysis in this experiment exhibited that the phases in the circadian behavioral rhythm were shifted backwards. We also measured the NAD(+). level in the SCN, which was a mediator regulating the mPer2 expression. Then, significant increase of NAD(+) was detected under the anesthesia. These results indicate that the anesthesia induces the increase of NAD(+), and consequently leads to the repression of mPer2 expression and modifies the circadian expression pattern and diurnal behavioral rhythm of mice. Furthermore, the modification of mPer2 expression by the anesthesia is considered to affect various gene expressions. (C) 2011 Elsevier Ireland Ltd. All rights reserved.

DOI： 10.1016/j.neulet.2010.12.059

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：BIOMEDICAL RESEARCH PRESS LTD  

Previous studies suggest that propofol and sevoflurane anaesthesia in rats may have variable effects on the proteome. Brains from untreated rats and rats anaesthetised with intravenous propofol infusion or inhaled sevoflurane were collected at various time points post-anaesthesia and subjected to global protein expression profiling using two-dimensional gel electrophoresis. Significant changes in protein spot intensity (i.e. expression) between the propofol and sevoflurane groups demonstrated clear similarities and differences in proteomic regulation by these anaesthetics. The proteins regulated were broadly classified into groups involved in cytoskeletal/neuronal growth, cellular metabolism, signalling, and cell stress/death responses. Proteins concerned with cell death and stress responses were down-regulated by both agents, but the anaesthetics had variable effects on proteins in the other groups. Importantly, proteins such as Ulip2 and dihydropyrimidinaseI ike-2 were regulated in opposite directions by propofol and sevoflurane. Moreover, the time-course of regulation of proteins varied depending on the agent used. These data suggest different underlying mechanisms of proteomic regulation. We found that sevoflurane anaesthesia had more pronounced effects, on a wider range of proteins, and over an apparently longer duration than propofol. Thus, sevoflurane could be considered a more disruptive anaesthetic agent. Our findings show that protein expression is regulated differentially according to the anaesthetic agent and the method of delivery support and extend our previous observations of differential genomic regulation by anaesthetics in the brain. This study highlights the power of proteomic studies in assessing the effects of certain anaesthetics on the integrity of neuronal structure and function.

DOI： 10.2220/biomedres.32.55

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：BIOMED CENTRAL LTD  

Background: Local anesthetics alleviate neuropathic pain in some cases in clinical practice, and exhibit longer durations of action than those predicted on the basis of the pharmacokinetics of their blocking effects on voltage-dependent sodium channels. Therefore, local anesthetics may contribute to additional mechanisms for reversal of the sensitization of nociceptive pathways that occurs in the neuropathic pain state. In recent years, spinal glial cells, microglia and astrocytes, have been shown to play critical roles in neuropathic pain, but their participation in the analgesic effects of local anesthetics remains largely unknown.
Results: Repetitive epidural administration of ropivacaine reduced the hyperalgesia induced by chronic constrictive injury of the sciatic nerve. Concomitantly with this analgesia, ropivacaine suppressed the increases in the immunoreactivities of CD11b and glial fibrillary acidic protein in the dorsal spinal cord, as markers of activated microglia and astrocytes, respectively. In addition, epidural administration of a TrkA-IgG fusion protein that blocks the action of nerve growth factor (NGF), which was upregulated by ropivacaine in the dorsal root ganglion, prevented the inhibitory effect of ropivacaine on microglia, but not astrocytes. The blockade of NGF action also abolished the analgesic effect of ropivacaine on neuropathic pain.
Conclusions: Ropivacaine provides prolonged analgesia possibly by suppressing microglial activation in an NGF-dependent manner and astrocyte activation in an NGF-independent manner in the dorsal spinal cord. Local anesthetics, including ropivacaine, may represent a new approach for glial cell inhibition and, therefore, therapeutic strategies for neuropathic pain.

DOI： 10.1186/1744-8069-7-2

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記述言語：日本語   出版者・発行元：(一社)日本集中治療医学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：BIOMEDICAL RESEARCH PRESS LTD  

Some reports have shown that electroconvulsive shock therapy (ECT) is effective for treating refractory neuropathic pain. However, its mechanism of action remains unknown. We have previously shown that electroconvulsive shock (ECS) improved thermal hypersensitivity in chronic constrictive injury (CCI) model rats and simultaneously elevated the neuropeptide Y (NPY) expression in the brain of these rats. In this study, we examined changes in the expression of NPY in the spinal cord of a CCI model. The rat model of CCI was established by ligating the left sciatic nerve. ECS was administered to the rats once daily for six days on days 7-12 after the operation using an electrical stimulator. RT-PCR was used to measure NPY mRNA expression in both the right and left L5 dorsal spinal cords on the 14th day after the operation. NPY gene expression was decreased in the dorsal spinal cords after ECS; however, no differences in NPY expression were observed between the right and left side of dorsal spinal cords, suggesting that the effect of changes in NPY expression after ECS on the improvement of neuropathic pain is not directly related to the spinal cord, but mainly to the upper central nerves.

DOI： 10.2220/biomedres.31.287

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記述言語：日本語   出版者・発行元：日本臨床麻酔学会  

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記述言語：日本語   出版者・発行元：(一社)日本心臓血管麻酔学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PUBLIC LIBRARY SCIENCE  

Background: General anesthesia is routinely used as a surgical procedure and its safety has been endorsed by clinical outcomes; however, its effects at the molecular level have not been elucidated. General anesthetics influence glucose metabolism in the brain. However, the effects of anesthetics on brain metabolites other than those related to glucose have not been well characterized. We used a pattern recognition analysis of proton nuclear magnetic resonance spectra to visualize the changes in holistic brain metabolic phenotypes in response to the widely used intravenous anesthetic propofol and the volatile anesthetic isoflurane.
Methodology/Principal Findings: Rats were randomized into five groups (n = 7 each group). Propofol and isoflurane were administered to two groups each, for 2 or 6 h. The control group received no anesthesia. Brains were removed directly after anesthesia. Hydrophilic compounds were extracted from excised whole brains and measured by proton nuclear magnetic resonance spectroscopy. All spectral data were processed and analyzed by principal component analysis for comparison of the metabolite profiles. Data were visualized by plotting principal component (PC) scores. In the plots, each point represents an individual sample. The propofol and isoflurane groups were clustered separately on the plots, and this separation was especially pronounced when comparing the 6-h groups. The PC scores of the propofol group were clearly distinct from those of the control group, particularly in the 6-h group, whereas the difference in PC scores was more subtle in the isoflurane group and control groups.
Conclusions/Significance: The results of the present study showed that propofol and isoflurane exerted differential effects on holistic brain metabolism under anesthesia.

DOI： 10.1371/journal.pone.0011172

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER JAPAN KK  

Negative pressure pulmonary edema (NPPE) is a noncardiogenic pathological process that is treated with invasive ventilation via a tracheal tube. To investigate the feasibility and safety of noninvasive positive pressure ventilation (NPPV) as an alternative treatment for NPPE, we retrospectively reviewed charts of 15 perioperative NPPE patients. Eight patients were treated by NPPV and 7 were treated by invasive ventilation. Patient characteristics, duration of NPPV, duration of intensive care unit (ICU) stay, and maximum airway pressure were investigated for the NPPV-treated patients. All patients treated by NPPV had a patent airway after complete relief of the airway obstruction and recovered from NPPE symptoms within one postoperative day. Arterial blood gas analysis showed a significant improvement in the PaO2/FiO(2) ratio from 132 +/- A 30 mmHg in the operating room to 282 +/- A 77 mmHg at discontinuation of NPPV. Serious complications, such as ventilator-associated pneumonia or aspiration pneumonia, did not occur, and intubation was not required for any patient. Favorable outcomes in these cases suggest that NPPV could be a feasible and safe alternative for treating NPPE if the patency of the airway is restored.

DOI： 10.1007/s00540-010-0899-0

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記述言語：日本語   出版者・発行元：医学図書出版(株)  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Impaired selective turnover of p62 by autophagy causes severe liver injury accompanied by the formation of p62-positive inclusions and upregulation of detoxifying enzymes. These phenotypes correspond closely to the pathological conditions seen in human liver diseases, including alcoholic hepatitis and hepatocellular carcinoma. However, the molecular mechanisms and pathophysiological processes in these events are still unknown. Here we report the identification of a novel regulatory mechanism by p62 of the transcription factor Nrf2, whose target genes include antioxidant proteins and detoxification enzymes. p62 interacts with the Nrf2-binding site on Keap1, a component of Cullin-3-type ubiquitin ligase for Nrf2. Thus, an overproduction of p62 or a deficiency in autophagy competes with the interaction between Nrf2 and Keap1, resulting in stabilization of Nrf2 and transcriptional activation of Nrf2 target genes. Our findings indicate that the pathological process associated with p62 accumulation results in hyperactivation of Nrf2 and delineates unexpected roles of selective autophagy in controlling the transcription of cellular defence enzyme genes. © 2010 Macmillan Publishers Limited. All rights reserved.

DOI： 10.1038/ncb2021

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記述言語：日本語   出版者・発行元：(一社)日本集中治療医学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Medical Association of Nippon Medical School  

Background: Atrial natriuretic peptide (ANP) plays important roles in the regulation of cardiovascular and renal homeostasis. Furthermore, several studies have shown that ANP may have anti-inflammatory activities. We hypothesized that ANP may alleviate cardiovascular and/or metabolic disorders in rats with lipopolysaccharide (LPS)-induced endotoxemia. Methods: In rats anesthetized with pentobarbital, LPS was injected and ANP was continuously infused at 0.15 μg/kg/min. Mean arterial pressure and pulse rate were monitored hourly, and arterial blood gases were analyzed before LPS injection and at 1, 4, and 6 hours after LPS injection. The expression in the rat left ventricle of mRNAs encoding nitric oxide synthase 2 and 3 (iNOS, eNOS), heme oxygenase 1 and 2 (HO-1, 2), tumor necrosis factor α (TNFα), and interleukin (IL)-1β was measured with the real-time reverse transcriptasepolymerase chain reaction. Results: LPS increased the expression of TNFα, IL-1β, iNOS, and HO-1, which was inhibited by infusion of ANP. Furthermore, the LPS-induced decrease in mean arterial pressure was attenuated, and the acid-base imbalance caused by increased lactate production was improved 6 hours after the administration of ANP. Conclusions: Our results suggest that continuous infusion of ANP counteracts the cardiovascular and metabolic disorders associated with endotoxemia, possibly via antiinflammatory mechanisms.

DOI： 10.1272/jnms.77.296

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Medical Association of Nippon Medical School  

Titration of oral or intravenous medication is the preferred method of pain management for most patients with cancer pain. However, some patients experience insufficient pain relief or considerable adverse effects from systemic opioids. For these reasons, the control of severe cancer pain continues to present a variety of challenges to clinicians. We report our experience of successfully managing cancer pain in a patient by means of long-term intrathecal administration of morphine, bupivacaine, and racemic ketamine via a patient-controlled delivery system. This therapy reduced the patient's nausea, vomiting, and somnolence, led to early hospital discharge, and increased her level of daily activity. There were no signs of motor paralysis, psychomimetic alteration, neurological dysfunction, or infection related to the intrathecal route during treatment. Intrathecal therapy is an effective treatment in terminally ill patients.

DOI： 10.1272/jnms.77.333

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY-BLACKWELL  

Objectives. Electroconvulsive shock therapy (ECT) has been widely used as an effective and established treatment for refractory depression and schizophrenia. Some reports have shown that ECT is also effective for treating refractory neuropathic pain.
Design. In a rat model of neuropathic pain produced by chronic constrictive injury (CCI) of the sciatic nerve, thermal hyperalgesia, and mechanical allodynia were observed from day 2 after surgery. An electroconvulsive shock (ECS) was administered to rodents once daily for 6 days on days 7-12 after CCI operation using a pulse generator. Thermal and mechanical stimulation tests were performed to assess pain thresholds. Real-time polymerase chain reaction was used to measure the gene expression levels for 5HT(1A)R, 5HT(2A)R, neuropeptide Y (NPY), and GABAA(alpha 1)R in the brain.
Results. After ECS, the latency to withdrawal from thermal stimulation was significantly increased; however, pain withdrawal thresholds in response to mechanical stimulation were not significantly changed. Expression ratios of NPY were significantly greater after ECS.
Conclusion. Symptoms of neuropathic pain improved and expression of NPY in the brain was increased in CCI model rats after ECS, suggesting that changes in the expression of NPY in the brain may be related to the mechanism of action of ECT in treating neuropathic pain.

DOI： 10.1111/j.1526-4637.2009.00678.x

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

Transfusion for hemorrhagic shock can improve oxygenation, but immunoreactions may induce inflammation. Artificial oxygen carriers have been developed to address clinical concerns of infection and stability, but whether an artificial oxygen carrier might induce inflammation is not well known. To address this question, we compared inflammatory reactions after resuscitation with hemoglobin vesicles (HbVs) or red blood cells (RBCs) in a hemorrhagic shock rat model. Both HbVs and the stored and irradiated rat RBCs deprived of huffy coat were suspended in recombinant human serum albumin [(Hb) = 8.6 g/dL]. Under anesthesia, hemorrhagic shock was induced for 30 min, followed by resuscitation by 20 min transfusion of HbVs or rat RBCs in a volume equivalent to the volume of withdrawn blood. Lungs were excised 2 or 24 h after resuscitation, and mRNA levels of tumor necrosis factor alpha (TNF-alpha), intercellular adhesion molecule-1 (ICAM-1), nitric oxide synthase 2 (iNOS), nitric oxide synthase 3, hypoxia-inducible factor 1 alpha, and heme oxygenase 1 (HO-1) were measured. In rats resuscitated with HbVs, mRNA levels of TNF-a and HO-1 2 h after resuscitation were significantly higher than those in the rat RBC group, but the levels at 24 h were similar in both groups. The expression of iNOS and ICAM-1, second messengers of inflammation, was not affected, and inflammatory levels after 24 h with HbVs are similar to rat RBC transfusion. The rat RBC group did not show an expected inflammatory reaction related to a transfusion-induced lung injury, and a clinical relevance concerning this level of transient inflammatory reaction induced by HbVs is not known; however, attention to the early stage of resuscitation in ongoing studies of HbV is required. ASAIO Journal 2009; 55: 478-483.

DOI： 10.1097/MAT.0b013e3181b17f34

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：NATURE PUBLISHING GROUP  

Sustained hemodynamic stresses, especially high blood flow, result in flow-induced outward vascular remodeling. Our previous study showed that macrophage depletion reduced flow-induced outward remodeling of the rat common carotid artery, indicating that macrophages are critical in flow-induced outward vascular remodeling. Macrophage is known to release proteinases, including matrix metalloproteinases (MMPs). Degradation and loosening of extracellular matrix by MMPs may facilitate vascular remodeling. Therefore, we assessed the functions of MMPs in flow-induced outward vascular remodeling by using the flow-augmented common carotid artery model in mice. We validated that ligation of the left common carotid artery increased blood flow and luminal diameter of the right common carotid artery without significant change in blood pressure of mice. To assess the functions of MMPs in flow-induced outward vascular remodeling, we used doxycycline (broad-spectrum MMP inhibitor), SB-3CT (selective MMP inhibitor), MMP-9 knockout mice, and MMP-12 knockout mice. Although there was only a trend for doxycycline treatment to reduce flow-induced outward vascular remodeling, SB-3CT treatment significantly reduced flow-induced outward vascular remodeling. In addition, flow-induced outward vascular remodeling was significantly reduced in MMP-9 knockout mice, but not in MMP-12 knockout mice. These data revealed that MMPs, especially MMP-9, are critical in flow-induced outward vascular remodeling. Journal of Cerebral Blood Flow & Metabolism (2009) 29, 1547-1558; doi:10.1038/jcbfm.2009.77; published online 10 June 2009

DOI： 10.1038/jcbfm.2009.77

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：BIOMEDICAL RESEARCH PRESS LTD  

The production of nitric oxide (NO) by inducible NO synthase (NOS) and carbon monoxide (CO) by inducible heme oxygenase (HO) contributes greatly to endotoxemia. Reciprocal relationships have been proposed between the NO/NOS and CO/HO systems. However, the interaction between these systems during endotoxemia is unclear, and it is unknown whether the interactive behavior differs among organs. Using endotoxic rats, we studied the effects of the inducible NOS (iNOS) inhibitor L-canavanine (CAN), and the HO inhibitor zinc protoporphyrin (ZPP) oil gene expression and protein levels of iNOS, endothelial NOS (eNOS), inducible HO (HO-1), and constitutive HO (HO-2) in the brain, lung, heart, liver and kidney tissue. Intravenous injection of LPS significantly increased iNOS and HO-1 gene expression in all organs. The effects of LPS on eNOS gene expression differed among organs, with increased expression in the liver and kidney, and no change in the lung, brain and heart. ZPP administration down-regulated the LPS-induced increase in HO-1 expression and produced a further increase in iNOS expression in all organs. These data suggest that the CO/HO system modifies the NO/NOS system in endotoxic organs, and that there were only minor organ-specific behaviors in terms of the relationship between these systems in the organs examined.

DOI： 10.2220/biomedres.30.235

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PERGAMON-ELSEVIER SCIENCE LTD  

Introduction: There are circadian genes whose expressions were affected by sevoflurane. We hypothesized that propofol and dexmedetomidine also have influences on the expressions of circadian genes.
Materials and methods: Seven-week-old rats were cannulated and propofol (600 mu g/kg/min, 1 ml/h, n = 6: group P6H), dexmedetomidine (1 mu g/kg/min, 1 ml/h, n = 6: group D6H), 10% lipid (1 ml/h, n = 6: group L) and normal saline (1 ml/h, n = 6: group N) were infused intravenously for 6 h; rats were decapitated soon or 24 h after awakening from anesthesia (groups P24H n = 6 and D24H n = 6). Real time reverse transcription-polymerase chain reaction was performed using rat whole brain and the expressions of circadian genes were measured.
Results: In the P6H group and the P24H group, the whole expressions of seven genes were changed significantly compared with the L group. In the D6H group, the whole expression of seven genes was changed significantly compared with the N group. In the P6H group, all gene expressions except for Tef (thyrotroph embryonic factor) were changed significantly compared with the L group. In this group, the expression of Dbp (D site albumin promoter binding protein) was increased, and the others were decreased. In the D6H group, all gene expressions except for Dbp and Tef were decreased significantly compared with the N group. For the two anesthetics, the expression patterns were different only in Dbp.
Conclusion: We showed that propofol and dexmedetomidine have influences on the circadian gene expressions. (C) 2009 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.brainresbull.2009.04.015

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCIENCE INC  

Study Objective: To determine whether administration of pre-warmed colloid followed by pre-warmed crystalloid solution prevents the development of hypothermia in patients undergoing Cesarean delivery.
Design: Randomized, double-blind, placebo-controlled study.
Patients: 30 parturients scheduled to undergo elective Cesarean delivery during spinal anesthesia.
Interventions: Patients assigned to the warmed fluid group (n = 15) received pre-warmed colloid with average molecular weight of 70,000 daltons and substitution ratio of 0.55, followed by pre-warmed crystalloid (kept in warmed storage maintained at 41 degrees C) during surgery. Patients assigned to the unwarmed fluid group (n = 15) received non-warmed infusion. All patients received 400 mL before spinal anesthesia followed by another 300 mL before delivery of the newborn. After completion of a 1,000 mL infusion of colloid fluid, acetate Ringer&apos;s solution was infused.
Measurements: Core temperature measured at the tympanic membrane, and forearm and fingertip skin temperatures were recorded just after arrival at the operating room (baseline), after administration of spinal anesthesia (spinal), at incision (incision), at delivery of the newborn, (delivery), and at 15, 30, and 45 minutes after delivery. Rectal temperature of the baby, Apgar scores at one and 5 minutes after delivery, and umbilical artery pH were evaluated.
Main Results: Core temperature was significantly higher in the unwarmed fluid group from the time of delivery to 45 minutes after delivery. Apgar scores at one minute after delivery and umbilical arterial pH were significantly higher in the warmed fluid group.

DOI： 10.1016/j.jclinane.2008.12.010

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

Dexmedetomidine hydrochloride is a potent, highly selective alpha-2 adrenergic receptor agonist, broadly used as a sedative drug in intensive care units. We describe the case of a 59-yr-old patient who experienced drug fever caused by dexmedetomidine hydrochloride. The patient was transferred to the intensive care unit with an abdominal aortic aneurysm rupture. After initiation of sedation with dexmedetomidine hydrochloride, he developed pyrexia of more than 39 degrees C. This symptom improved rapidly 7 h after stopping dexmedetomidine hydrochloride. Other possible causes (such as infection) were sequentially eliminated.

DOI： 10.1213/ane.0b013e31819f1985

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記述言語：日本語  

Protective effects of each cardiovascular drug on major organ functions are reviewed. Based on these effects, proper use of the drugs is presented. It is probable that norepinephrine and dobutamine have the most protective effect against major organ dysfunctions. It has been shown that perioperative beta- blocker administration reduces cardiovascular complications. Nicorandil is likely to have ischemic preconditioning properties. In case of hypotension, low doses of noradrenaline should be administered first, and then dobutamine should be added. In case of systolic dysfunction, low doses of dobutamine should be chosen first, and then noradrenaline, and finally olprinone could be added. In case of hypotension and systolic dysfunction, a combination of norepinephrine and dobutamine is the first choice. Then adrenaline could be added. When ischemic heart disease exists, nicorandil should be given. When decreasing or stabilizing heart rate is required, an ultra-short acting beta-blocker, such as lan- diolol, is recommended. To maintain hypotension in a certain situation, prostaglandin E 1 is better to use than nicardipine, diltiazem, and nitroglycerin. It is important to administer the drugs focusing on postoperative complications and outcome.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：BIOMEDICAL RESEARCH PRESS LTD  

We previously showed that sevoflurane anesthesia affected the expression ratios of 177 of 10,000 genes in multiple organs of rats by microarray analyses. The maximum number of altered genes was detected in the liver. and included several genes characterized as encoding drug-metabolizing enzymes (DMEs). Here, we investigated whether alterations of pharmacokinetic gene expressions after anesthesia differed between inhalation and intravenous anesthesia, and how long the alterations persisted after awakening from anesthesia. Livers were obtained from rats (n = 6 per group) anesthetized with sevoflurane, isoflurane, propofol or dexmedetomidine for 0 or 6 h, and rats awakened for 24 h after anesthesia for 6 h. The mRNA expression ratios of eight genes encoding DMEs that showed the greatest alterations in the previous study, namely Cyp7a1, Cyp2b15, Por, Nr1i2, Ces2, Ugt1a7,-Abcb1a and Abcc2, were measured by quantitative real-time reverse transcriptase-polymerase chain reaction. The expression ratios were mostly increased after 6 h of anesthesia and returned to their control levels at 24 h after awakening from anesthesia. However, the expression ratios of some genes remained elevated for 24 h after awakening from anesthesia. There were differences between inhalation and intravenous anesthesia, and interestingly, between sevoflurane and isoflurane and between propofol and dexmedetomidine.

DOI： 10.2220/biomedres.30.17

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

We previously showed that sevoflurane anesthesia affected the expression ratios of 177 of 10,000 genes in multiple organs of rats by microarray analyses. The maximum number of altered genes was detected in the liver, and included several genes characterized as encoding drug-metabolizing enzymes (DMEs). Here, we investigated whether alterations of pharmacokinetic gene expressions after anesthesia differed between inhalation and intravenous anesthesia, and how long the alterations persisted after awakening from anesthesia. Livers were obtained from rats (n = 6 per group) anesthetized with sevoflurane, isoflurane, propofol or dexmedetomidine for 0 or 6 h, and rats awakened for 24 h after anesthesia for 6 h. The mRNA expression ratios of eight genes encoding DMEs that showed the greatest alterations in the previous study, namely Cyp7a1, Cyp2b15, Por, Nr1i2, Ces2, Ugt1a7, Abcb1a and Abcc2, were measured by quantitative real-time reverse transcriptase-polymerase chain reaction. The expression ratios were mostly increased after 6 h of anesthesia and returned to their control levels at 24 h after awakening from anesthesia. However, the expression ratios of some genes remained elevated for 24 h after awakening from anesthesia. There were differences between inhalation and intravenous anesthesia, and interestingly, between sevoflurane and isoflurane and between propofol and dexmedetomidine.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

We have designed a new curved laryngoscope blade based on a new concept of reversing the peardrop phenomenon to facilitate a view of the larynx sufficient for intubation in a greater variety of patients than the current Macintosh blade affords. The new design has a bifid tip and S-shaped spatula to exert more effective pressure in the vallecula area, elevate the epiglottis and change directions of the forces on the tongue to prevent posteroinferior displacement of the compressed tongue in the submandibular space during laryngoscopy. A radiograph laryngoscopy technique was used to guide the new blade curvature design and compare the performance of the new blade with the Macintosh blade in patients with or without a difficult airway. Our results confirm that the new blade provides a laryngeal view sufficient to accomplish intubation by compressing the root of the tongue in an anterocephalad direction in the submandibular space and elevating the epiglottis effectively in patients with or without unanticipated difficult airway. The new curved blade can also effectively move the U-shaped epiglottis out of the laryngeal view to facilitate intubation in pediatric patients aged 2 mo-13 yr.

DOI： 10.1213/ane.0b013e318185cecb

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：BIOMEDICAL RESEARCH PRESS LTD  

The purpose of the present study was to evaluate the effect of dexmedetomidine, used as a sedative in the intensive care unit, on human neutrophil apoptosis and superoxide production in vitro. Neutrophils from healthy volunteers were incubated in different concentrations of dexmedetomidine (1, 10 and 100 ng/mL). Apoptosis was assessed by Hoechst 33342 staining, caspase activities and loss of mitochondrial transmembrane potential (MTP). Superoxide production was determined by the WST-1 assay. After 24 h of incubation, dexmedetomidine accelerated neutrophil apoptosis in a dose-dependent manner and 100 mu M yohimbine did not inhibit the apoptosis. Treatment with 100 ng/mL of dexmedetomidine significantly enhanced the activation of caspases-3/7, -8 and -9, and also markedly increased the number of neutrophils with decreased MTP. At 24 h, the suppression of superoxide production was dependent on dexmedetomidine concentrations. However, a clinically relevant concentration (I ng/mL) of dexmedetomidine did not affect neutrophil apoptosis and superoxide production. These results suggest that high doses of dexmedetomidine induce lapoptosis without alpha(2)-adrenoceptors stimulus and inhibit superoxide production after long-term incubation. The mechanisms of dexmedetomidine-induced apoptosis are associated with the caspase cascade and loss of MTP.

DOI： 10.2220/biomedres.29.189

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER TOKYO  

Purpose. Noninvasive ventilation (NIV) has been successfully used to treat various forms of acute respiratory failure. It remains unclear whether NIV has potential as an effective therapeutic method in patients with acute lung injury (ALI). The aims of this study were to determine factors predicting the need for endotracheal intubation in ALI patients treated with NIV, and to promote the selection of patients suitable for NIV.
Methods. We conducted a retrospective study of all patients admitted to the intensive care unit (ICU) of the Nippon Medical School Hospital from 2000 to 2006 with a diagnosis of ALI, in whom NIV was initiated.
Results. A total of 47 patients with ALI received NIV, and 33 patients (70%) successfully avoided endotracheal intubation. Patients who required endotracheal intubation had a significantly higher Acute Physiology and Chronic Health Evaluation (APACHE) II score and a significantly higher Simplified Acute Physiology Score (SAPS) II, and a significantly lower arterial pH. The respiratory rate decreased significantly within 1 h of starting NIV only in patients successfully treated with NIV. An APACHE II score of more than 17 (P = 0.022) and a respiratory rate of more than 25 breaths.min(-1) after 1 h of NIV (P = 0.024) were independent factors associated with the need for endotracheal intubation. Patients who avoided endotracheal intubation had a significantly lower ICU mortality rate and in-hospital mortality rate than patients who required endotracheal intubation.
Conclusion. We determined an APACHE II score of more than 17 and a respiratory rate of more than 25 breaths.min(-1) after 1 h of NIV as factors predicting the need for endotracheal intubation in ALI patients treated with NIV.

DOI： 10.1007/s00540-008-0637-z

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

BACKGROUND: Agitation is associated with failure of noninvasive ventilation (NIV). We investigated the effect of dexmedetomidine in patients with NIV.
METHODS: This was a prospective clinical investigation in an intensive care unit. Dexmedetomidine was infused in 1.0 patients in whom NIV was difficult because of agitation.
RESULTS: Ramsay and Richmond Agitation-Sedation Scale scores were maintained at 2.94 +/- 0.94 and -1.23 +/- 1.30, respectively. All patients were successfully weaned from NIV, and the respiratory state was not worsened.
CONCLUSION: This study shows that dexmedetomidine is an effective sedative drug for patients with NIV.

DOI： 10.1213/ane.0b013e3181732dc2

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：OXFORD UNIV PRESS  

Background. Sevoflurane is a fluorinated volatile anaesthetic agent that lowers arterial pressure, in part by vasodilation. We previously showed, in rat lungs, that sevoflurane affected the expression of endothelin-1 (ET-1), a potent vasoconstrictor peptide. Therefore, we hypothesized that the vasodilation induced by sevoflurane involved vasodilatory and vasoconstrictor components.
Methods. Rats were anaesthetized with sevoflurane 4% for 0, 2, and 6 h (n=9 each group) before death. In addition, a further group (n=9) were anaesthetized for 6 h then awoken for 2 h before death (n=9). We measured expression of mRNA encoding ET-1, nitric oxide synthase-1, 2, 3 (NOS1, 2, 3), haeme oxygenase-1, 2 (HO-1, 2), adrenomedullin (ADM), calcitonin gene-related peptide, vasoactive intestinal peptide, and prostacyclin synthase in whole lung using real-time reverse transcriptase-polymerase chain reaction.
Results. Expressions of ET-1 and ADM were significantly increased by inhalation of sevoflurane for 2 and 6 h (P &lt; 0.05). Expression of NOS3 was significantly increased at 6 h (P &lt; 0.05). After awaking from anaesthesia, the expressions of NOS3, ET-1, and ADM returned to baseline levels.
Conclusions. Sevoflurane increased the expressions of ET-1, NOS3, and ADM. Our results suggest that the increased expressions of NOS3 and ADM may counteract that of ET-1 and so regulate pulmonary circulation under sevoflurane anaesthesia.

DOI： 10.1093/bja/aem347

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCIENCE BV  

Propofol is a commonly used anesthetic agent, and it attenuates hypoxic ventilatory response in humans. Propofol reduce in vivo and in vitro carotid body responses to hypoxia as well as to nicotine in experimental animals. In the present study we examined the effects of propofol on carotid body responses to hypercapnia and K+-induced carotid body activation and compared these effects with hypoxia in an in vitro rabbit carotid body preparation. Hypoxia, hypercapnia and potassium increased the carotid sinus nerve activity and propofol attenuated the chemoreceptor responses to all three stimuli. However, the magnitude of propofol-induced attenuation was greater for hypercapnic and K+-induced carotid body activation compared to the hypoxic response. These observations suggest that propofol-induced attenuation of the hypoxic response is partly secondary to depression of chemoreceptor response to hypercapnia inhibiting the synergistic interactions between O-2 and CO2 and may involve CO2/H+ sensitive K+ channels. (C) 2007 Elsevier B.V. All rights reserved.

DOI： 10.1016/j.resp.2007.10.011

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER TOKYO  

Beta-adrenergic receptor blockers have proved to be effective for the management of various cardiovascular diseases and the prevention of perioperative cardiac events and cerebrovascular accidents. Landiolol is a short-acting beta-blocker, with high beta 1-selectivity and a short duration of action. We thought landiolol was valuable and suitable for intensive care unit (ICU) patients, and conducted a retrospective study. The records of 80 patients (58 post-surgical patients; group S and 22 internal medicine patients; group IM) were reviewed. Thirty-seven (64%) of the group S patients were post-coronary artery bypass graft surgery, and the IM group consisted mostly of patients with acute myocardial infarction. The most common indication for landiolol in group S was the prevention of myocardial ischemia (50%), and in group IM, it was atrial fibrillation (45%). The median infusion rate of landiolol was 5 mu g.kg(-1).min(-1) and the median infusion time was 2 days. Twenty-six patients were continued on oral beta-adrenergic receptor blockers. Landiolol reduced heart rate significantly without reducing blood pressure, and stabilized hemodynamics. We confirmed that landiolol is valuable as a bridge to starting oral beta-adrenergic receptor blockers and as an anti-arrhythmic agent, and that it is suitable for ICU patients due to its high beta 1-selectivity and rapid onset and offset of action.

DOI： 10.1007/s00540-007-0573-3

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

BACKGROUND: In clinical practice, the analgesic effects of epidurally administered local anesthetics on chronic pain sometimes outlast the duration of drug action expected from their pharmacokinetics. To investigate the underlying mechanisms of this prolonged effect, we examined the effects of ropivacaine, a local anesthetic, on pain-related behavior in a rat model of neuropathic pain. We also analyzed changes in the expression of nerve growth factor (NGF), which is involved in plasticity of the nociceptive circuit after nerve injury.
METHODS: In a rat model of neuropathic pain produced by chronic constrictive injury (CCI) of the sciatic nerve, thermal hyperalgesia, and mechanical allodynia were observed from Day 3 after surgery. Ropivacaine or saline was administered through an epidural catheter once a day, every day, and from Days 7-13 after the CCI operation. NGF content was measured in the L4 dorsal root ganglion, the hindpaw skin, the L4/5 dorsal spinal cord, and the sciatic nerve, using enzyme immunoassay.
RESULTS: The latency to withdrawal from thermal stimuli on the ipsilateral paw pads of CCI rats was significantly increased 4 days after the beginning of ropivacaine treatment, and thermal hyperalgesia was almost fully relieved. Similarly, mechanical allodynia was partially reduced after ropivacaine treatment. NGF content was increased in the L4 dorsal root ganglion on the ipsilateral, but not the contralateral, side, in CCI rats treated with ropivacaine.
CONCLUSION: Repetitive administration of ropivacaine into the epidural space in CCI rats exerts an analgesic effect, possibly by inducing a plastic change in the nociceptive circuit.

DOI： 10.1213/01.ane.0000296460.91012.51

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

Background : For anesthetic management of traditional open prostatectomy, preparation for hemorrhage is necessary. However, it has been considered that the amount of bleeding under laparoscopic prostatectomy is less than that of traditional open surgery. Methods : The amount of bleeding and autologous blood preparation, fluid balance, and anesthetic management were investigated in patients who had undergone laparoscopic or open prostatectomy at the Nippon Medical School Hospital between June, 2004 and November, 2005, retrospectively. The difference of these aspects between the two surgical method groups was evaluated. Results : Thirty-two patients underwent prostatectomy in the investigation period. In these patients, 4 patients were excluded due to incomplete anesthesia record or change of surgical method. The amount of bleeding, and both amount of autologous blood preparation and transfusion in the laparoscopic surgery were less than those in the open surgery. There were no significant differences in the fluid balance and amount of urine output between the two groups. Conclusions : We conclude that preparation of autologous blood transfusion is necessary for the traditional open prostatectomy, but not for the laparoscopic prostatectomy.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCIENCE BV  

General anesthesia is routinely used as a surgical procedure and its safety has been endorsed by clinical outcomes; however, its effects at the molecular level have not been elucidated. We previously showed that inhalation anesthesia affects the expression of 1.5% of 10,000 genes, which included so-called circadian genes. In the current study, we confirmed that inhalation of sevoflurane alters circadian gene expression, and investigated whether this alteration persists after awakening from anesthesia. Rats were anesthetized with 4.0% sevoflurane for 0 h, 2 h and 6 h (n = 9 each group), before being sacrificed. Rats were also anesthetized for 6 h and allowed to recover after anesthesia, then sacrificed 2 h, 6 h and 24 h after awakening (n = 9 each group). Anesthesia was started for each group so that all rats would be sacrificed at 13:00, and gene expression in the whole brain was examined using real-time RT-PCR. Expression of the genes encoding Per2, Dbp, Arc, Egr1, Krox20 and NGFI-B was suppressed during inhalation of sevoflurane for 2 h and 6 h. Although the suppression tended to be alleviated after awakening from anesthesia, the expression levels after a recovery period of 24 h remained significantly lower than the control levels of these genes, except for Krox20. We demonstrated that circadian gene expression is suppressed in whole brain during sevoflurane anesthesia, and the suppression continues for at least 24 h after termination of sevoflurane treatment. This suggests that sevoflurane anesthesia may have effects at the molecular level and that these effects are long lasting. (C) 2007 Elsevier B.V. All rights reserved.

DOI： 10.1016/j.brainres.2007.09.011

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：W B SAUNDERS CO-ELSEVIER INC  

Background: A common problem during lung separation is malposition of the double-lumen tube (DLT). It was hypothesized that inflation of the distal cuff with saline instead of air may reduce the incidence of malposition of the endobronchial tube.
Materials and Methods: Fifty-two patients who were scheduled to undergo thoracic surgery with lung separation by a DLT were randomly assigned to 1 of 2 groups: the distal cuff was inflated with 2 mL of air in the air group (n = 26), whereas the distal cuff was inflated with 1.2 mL of saline in the saline group (n = 26). Anesthesia was maintained by isoflurane, 50% oxygen and nitrous oxide mixture, and incremental injection of epidural ropivacaine, 0.75%. Respiration was controlled by pressure-controlled ventilation. The peak airway pressure was maintained between 20 to 25 cmH(2)O. The position of the bronchial cuff was evaluated with a fiberoptic bronchoscope just after intubation and 1 and 2 hours after intubation by using a 3-point scale: 0, in exactly the same position as the previous inspection; 1, not in exactly the same position as that in the previous inspection, but there was no possibility that the tube was malpositioned; and 2, the cuff looked as if it was going to become herniated or dislodged. Signs suggesting malposition such as air leakage, high airway pressure, or inflation of the independent lung were recorded. When repositioning was required, the anesthesiologist repositioned the DLT using bronchoscopic observation or clinical signs. The endpoint of this study was the number of patients who required repositioning during surgery.
Results: The malposition score at 1 hour and 2 hours after intubation was comparable in the 2 groups (0.6 +/- 0.6 v 0.4 +/- 0.6 and 0.5 +/- 0.8 v 0.2 +/- 0.5, mean +/- standard deviation, air group v saline group, 1 hour and 2 hours after positioning, p = 0.27 and p = 0.33, respectively). However, a significantly higher cumulative number of air-group patients required repositioning of the tube than saline-group patients (13:6, air group:saline group, p = 0.04).
Conclusion: Inflation of the distal cuff with saline may reduce the incidence of malpositioning of DLTs during lung separation. (C) 2007 Elsevier Inc. All rights reserved.

DOI： 10.1053/j.jvca.2006.11.014

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：BLACKWELL PUBLISHING  

Electroconvulsive therapy (ECT) is an effective and safe treatment for a variety of neuropsychiatric disorders. Premedication with atropine has been recommended in order to avoid bradycardia and transient asystole induced by ECT. In contrast, some other arrhythmias can happen such as atrial flutter and fibrillation. But ventricular tachycardia is rare. Reported herein is a case of incessant non-sustained ventricular tachycardia, possibly triggered by atropine premedication.

DOI： 10.1111/j.1440-1819.2007.01708.x

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER  

Purpose Negative-balance isolated pelvic perfusion (NIPP) is used to administer high doses of anticancer drugs such as cisplatin to patients with advanced cancer of the pelvic region. Although the drugs are intended to be specifically delivered to the pelvis, their leakage into the systemic circulation can cause acute renal failure. This study examines the loading volume required for preservation of renal function during anesthesia of NIPP.
Methods Pelvic cancer patients were assigned to NIPP according to its enrollment criteria. Patients with heart failure, uncontrollable hypertension, renal failure, pulmonary disease or contraindication for the contrast media were excluded. We compared the current anesthesia management regime with a previous protocol, with regard to the loading volume and renal function as assessed by the calculated glomerular filtration rate (GFR). The correlation between the total loading volume and the GFR ratio (GFR after NIPP/GFR before NIPP) was evaluated to define adequate volume loading.
Results The GFR ratios were 0.86 +/- 0.29 and 1.12 +/- 0.25 for the previous and current procedures, respectively. The regression line showed that a minimum loading volume of 28.8 ml kg(-1)h(-1) was required to maintain a GFR ratio of &gt;= 1.
Conclusions A large volume infusion preserves the GFR despite high-dose cisplatin administration by NIPP.

DOI： 10.1007/s00432-007-0217-x

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The authors applied near-infrared low-level laser irradiation (LLLI) directed to the stellate ganglion (SG) and to the common carotid artery (CCA), and compared the effects on central retinal artery blood flow using color pulse Doppler sonography. In 10 healthy volunteers, LLLI (0.92 W, 1 : 1 duty cycle, 10 min) to both the SG and CCA significantly increased peak systolic blood velocity in the ophthalmic artery (p&lt
0.001, each) and central retinal artery (p&lt
0.001, each) without changes in vessel resistance. Irradiation to the CCA produced a stronger effect than that to the SG in the ophthalmic artery (p=0.007) and central retinal artery (p=0.031). These data suggest that LLLI to the SG or to the CCA is a useful therapy for increasing the retrobulbar blood flow, with irradiation directed to the CCA being more effective than that directed to the SG in clinical settings.

DOI： 10.1272/jnms.74.23

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCIENCE INC  

Study Objective: To assess whether nicorandit reduces the likelihood of cardiac events during and after intermediate risk surgery.
Design: Multicenter study.
Setting: 13 hospitals in Japan.
Patients: Intermediate-risk patients were identified by the presence of risk factors such as angina, a history of myocardial infarction, heart failure, diabetes mellitus, and abnormal electrocardiography (ECG).
Interventions: Nicorandil was given to these patients during the operation.
Measurements and Main Results: Cardiac events during the operation and the following 5 days were monitored. The frequency of cardiac events in nicorandil-treated patients was compared with those in nontreated patients. Eighty-four patients received nicorandil during surgery and 237 patients received standard care. Cardiac events in the nicorandil-treated group occurred less frequently both during the operation (odds ratio, 0.15; 95% confidence interval, 0.03-0.76; P = 0.02) and after it (odds ratio, 0.24; 95% confidence interval, 0.06-0.90; P = 0.04).
Conciusions: Nicorandil reduces the frequency of cardiac events in patients undergoing noncardiac surgery, both during and after the operation. (C) 2007 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.jclinane.2006.05.023

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Medical Association of Nippon Medical School  

Background: Left ventricular (LV) diastolic function has received much attention recently. However, few studies have evaluated LV diastolic function in the perioperative period. The aim of this study was to elucidate perioperative changes in diastolic function using tissue Doppler imaging (TDI) in patients undergoing repair of an infrarenal abdominal aortic aneurysm (AAA). Methods: Eight patients undergoing repair of an infrarenal AAA were studied prospectively using transesophageal echocardiography. Doppler echocardiographic examinations were performed before the surgical procedure (T1), immediately before aortic unclamping (T2), 30 minutes after aortic unclamping (T3), and at the end of surgery (T4). Results: Pulmonary edema developed in two patients on postoperative day 1. These two patients had the lowest early diastolic mitral annular velocity (Ea) of the study group at the end of surgery. The ratio of the peak velocity of early mitral inflow (E) to the peak velocity of atrial inflow was significantly decreased at T3 and T4. The systolic ejection velocity was significantly decreased at T3, but returned to the baseline value at T4. The Ea was significantly decreased at T3 and T4. The E/Ea ratio showed a progressive rise and was significantly increased at T3 and T4. Conclusions: In patients undergoing repair of an infrarenal AAA, the Ea derived using TDI decreases at T3 and is still reduced at T4. The E/Ea ratio, which is used to estimate LV filling pressures, is significantly increased at T3 and T4. Further research is required to confirm the development of diastolic dysfunction and determine its possible association with increased postoperative morbidity and mortality.

DOI： 10.1272/jnms.74.393

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記述言語：英語   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：BIOMEDICAL RESEARCH PRESS LTD  

The aim of the present study was to compare the hypoxic and inflammatory effects of transfusing hemoglobin-vesicles (HbV) or lactated Ringer's (LR) solution on several organs in a hemorrhagic shock model. Hemorrhagic shock was induced in 48 anesthetized rats by withdrawing 28 mL/kg blood. The animals were resuscitated by replacing the blood with an equal volume of HbV solution or three times the volume of LR solution. The heart, lung, liver, kidney and spleen were extracted at different time points following resuscitation, and mRNA expression levels of hypoxia-induced factor 1-alpha (HIF-1 alpha) and tumor necrosis factor-alpha (TNF-alpha) were determined. Blood lactate concentrations in the HbV group rapidly returned to baseline levels, whereas elevated lactate concentrations in the LR group were prolonged. There were no significant differences between the two resuscitation groups in terms of HIF-1 alpha and TNF-alpha expression in the organs examined. HIF-1 alpha and TNF-alpha expression in the lungs was significantly greater than in other organs. Our results suggest that resuscitation from hemorrhagic shock with HbV did not increase hypoxic or inflammatory effects in major organs, compared with resuscitation using LR solution, despite prolonged elevation of blood lactate.

DOI： 10.2220/biomedres.27.283

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCIENCE INC  

PURPOSE: To determine the effect of ophthalmic viscosurgical devices (OVDs) and irrigation/aspiration (I/A) settings on free radical development during phacoemulsification.
SETTING: Department of Ophthalmology, Nippon Medical School, Tokyo, Japan.
METHODS: Free radicals were detected by the electron spin resonance (ESR) spin-trap method. After a spin-trapping agent, 5,5-dimethyl-1-pyrroline N-oxide 1%, was mixed with the irrigating solution, phacoemulsification simulation was performed in an eye model at 100% ultrasound power levels for 10, 20, and 30 seconds. A high I/A setting (35 mL/min with 250 mm Hg vacuum) and a low I/A setting (15 mL/min with 60 mm Hg vacuum) were used in combination with no OVD, sodium hyaluronate 1% (Healon), sodium hyaluronate 2.3% (Healon5), sodium hyaluronate 3%-chondroitin sulfate 4% (Viscoat), or sodium hyaluronate 1% (Opegan). Immediately after phacoemulsification, the solution in the anterior chamber was collected and signals from the spin adduct were measured using an ESR spectrometer.
RESULTS: With the low setting, all OVDs significantly suppressed the signals for up to 20 seconds. At 30 seconds, the signals were still significantly smaller in all OVD groups, except Healon, than those in the no-OVD. With the high setting, the effect was not significant in the Healon and Opegan groups at 10 seconds; by 20 seconds and after, only Viscoat showed significant suppression.
CONCLUSIONS: Free radical development in phacoemulsification can be altered by OVD properties and I/A settings. To reduce oxidative stress to the corneal endothelium, attention should be paid to the retention of OVDs in the anterior chamber during phacoemulsification.

DOI： 10.1016/j.jcrs.2006.04.026

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Here we report on a postoperative living-donor liver transplantation (LDLT) patient who received nightly infusions of dexmedetomidine (DEX), a specific α-adrenergic receptor agonist, to treat agitation and insomnia during an intensive care unit stay. The infusion rate was adjusted according to the Ramsay sedation score. The actual plasma concentrations were higher than the values predicted by RugLoop software package simulation 9h after the DEX infusion. However, all of the measurements were within the therapeutic range for DEX. Thus, DEX infusion could be safely used in the postoperative LDLT patient by employing a simple consciousness scale. © JSA 2006.

DOI： 10.1007/s00540-006-0409-6

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

Background. Ketamine potentiates intravenous or epidural morphine analgesia. The authors hypothesized that very-low-dose ketamine infusion reduces acute and long-term postthoracotomy pain.
Methods: Forty-nine patients scheduled to undergo open thoracotomy were randomly assigned to receive one of two anesthesia regimens: continuous epidural infusion of ropivacaine and morphine, along with intravenous infusion of ketamine (0.05 mg (.) kg(-1) (.) h(-1) [approximately 3 mg/h], ketamine group, n = 24) or placebo (saline, control group, n = 25). Epidural analgesia was continued for 2 days after surgery, and infusion of ketamine or placebo was continued for 3 days. Pain was assessed at 6, 12, 24, and 48 h after surgery. Patients were asked about their pain, abnormal sensation on the wound, and inconvenience in dally life at 7 days and 1, 3, and 6 months after surgery.
Results: The visual analog scale scores for pain at rest and on coughing 24 and 48 h after thoracotomy were lower in the ketamine group than in the control group (pain at rest, 9 11 vs. 25 +/- 20 and 9 +/- 11 as. 18 +/- 13; pain on coughing, 26 +/- 16 vs. 50 +/- 17 and 30 +/- 18 vs. 43 +/- 18, mean SD; P = 0.002 and P = 0.01, P &lt; 0.0001 and P = 0.02, respectively). The numerical rating scale scores for baseline pain 1 and 3 months after thoracotomy were significantly lower in the ketamine group (0.5 [0-4] us. 2 [0-5] and 0 [0-5] vs. 1.5 [0-6], median [range], respectively; P = 0.02). Three months after surgery, a higher number of control patients were taking pain medication (2 vs. 9; P = 0.03).
Conclusions: Very-low-dose ketamine (0.05 mg - kg(-1) - h(-1)) potentiated morphine-ropivacaine analgesia and reduced postthoracotomy pain.

DOI： 10.1097/00000542-200607000-00020

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

Objective: To examine the association between decreased release of proinflammatory cytokines in response to urinary trypsin inhibitor pretreatment and decreased myocardial and lung injury after cardiopulmonary bypass.
Design: A prospective, randomized, double-blind study.
Setting. University hospital.
Subjects: Thirty patients on cardiopulmonary bypass undergoing coronary artery bypass grafting.
Interventions: Patients received 5000 units/kg intravenous urinary trypsin inhibitor (n = 15) or 0.9% saline (control, n = 15) immediately before aortic carmulation for cardiopulmonary bypass.
Measurement and Main Results. Neutrophil elastase, tumor necrosis factor-alpha, interleukin-6, and interleukin-8 were measured after intubation (T1), immediately before aortic cannulation (T2), after separation from cardiopulmonary bypass (T3), at the end of surgery (T4), and on postoperative days 1 (T5), 3 (T6), and 5 (T7). Simultaneous hematocrit values were obtained at all sample times. lsoenzyme of creatine kinase with muscle and brain subunits, troponin-T, and myosin light chain I were also measured. Various hemodynamic and pulmonary data were obtained perioperatively. Levels of neutrophil elastase and cytokines were corrected for hemodilution. Interleukin-6 and interleukin-8 levels were lower at T3 and T4 in the urinary trypsin inhibitor group than in the control group. Stroke volume index was significantly decreased in the control group at T3, and statistical difference was found between groups at T3 (p &lt;.01). Respiratory index and intrapulmonary shunt were significantly higher in the control group than in the urinary trypsin inhibitor group at T3. Changes in respiratory index and intrapulmonary shunt correlated with interleukin-8 levels at T3 (r(2)=.52, p &lt; 00001; r(2)=.37, p &lt; 0001, respectively) and T4 (r(2)=.44, p &lt;.001; r(2)=.24, p &lt;.05, respectively). Neutrophil elastase levels and cardiac marker responses to coronary artery bypass grafting surgery were similar in both groups.
Conclusions: Prepump administration of urinary trypsin inhibitor attenuates the elevation of interleukin-6 and interleukin-8 release immediately after cardiopulmonary bypass.

DOI： 10.1097/01.CCM.0000215110.55899.AE

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Epidural anesthesia attenuates surgical stress responses, such as the immune reaction and the pituitary hormone response. In the present study, we investigated the leukocyte response to initial surgical stimulation during upper abdominal surgery. Twenty adult patients (American Society of Anesthesiologists physical status I-II) undergoing elective upper abdominal surgery were randomly assigned to an epidural anesthesia group or a general anesthesia group. An epidural catheter for postoperative pain relief was inserted into all patients before induction. In the epidural anesthesia group, patients obtained preemptive analgesia from Th4 to Th12 with 2% mepivacaine, whereas general anesthesia was maintained with 2 L of oxygen, 4 L of nitrous oxide, and 1% to 3% isoflurane. Changes in the leukocyte count and leukocyte subset distribution were determined before induction (baseline), immediately after induction, 5 minutes after induction, 5 minutes after skin incision, and 5 minutes after peritoneal incision. The changes were significantly different between the groups throughout the observation period (p&lt
0.0001). The general anesthesia group demonstrated an increase in the leukocyte count compared with the baseline data 5 minutes after skin incision and 5 minutes after peritoneal incision (p&lt
0.01). Moreover, these counts were significantly higher in the general anesthesia group than in the epidural anesthesia group (p&lt
0.05). The subset distributions were also significantly different between the groups throughout the observation period (p&lt
0.0001). In the general anesthesia group, neutrophils decreased and lymphocytes increased significantly compared with baseline (p&lt
0.05). Moreover, lymphocyte distribution was significantly higher in the general anesthesia group than in the epidural anesthesia group 5 minutes after peritoneal incision. Thus, anesthesia modifies the early response of leukocytes to surgical stress. The link between the early leukocyte response to surgery and postoperative outcome is the next subject of investigation.

DOI： 10.1272/jnms.73.4

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：BLACKWELL PUBLISHING  

Although the contribution of the gamma-aminobutyric acid (GABA) receptor system in peripheral chemosensation is unclear, immunohistochemistry has demonstrated the presence of GABA-ergic receptors in mammalian carotid bodies. We hypothesized that an activation of the carotid body GABA receptors would counteract the depolarizing effect of hypoxia.
The carotid body with arterial supply and the carotid sinus nerve was removed en bloc from New Zealand White rabbits and placed in a perfusion chamber. The carotid body preparation was perfused via the cut common carotid artery with a modified Tyrode's solution at a rate of 3.5-4.5 ml/min with a constant pressure of 45 cmH(2)O. The carotid sinus nerve firing frequency (Hz) was recorded at two different oxygen tension levels during perfusion with midazolam of 1, 10 and 100 mu g/l.
The frequency was decreased by midazolam in a dose-dependent manner (n = 8). Firing frequencies (mean +/- SEM) at the low oxygen tension level decreased from 643.13 +/- 67.2 Hz in the control to 554.5 +/- 67.7 Hz (P = 0.054 vs. control), 509.01 +/- 100.5 Hz (P &lt; 0.012 vs. control) and 422.6 +/- 77.3 Hz (P &lt; 0.001 vs. control) during perfusion with midazolam of 1, 10 and 100 mu g/l, respectively.
Midazolam depresses carotid body chemoreceptor activity in a dose-dependent manner.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

Several hemoglobin (Hb)-based oxygen carriers are available for use in clinical situations, but their use risks inducing cardiovascular dysfunction as a result of Hb interacting with nitric oxide. Hb vesicles (HbV) are liposome-encapsulated purified human Hb with polyethylene glycol chains at the surface. This study evaluated the effects of HbV on hemodynamics, tissue and systemic oxygenation, and osmotic pressure after fluid resuscitation in an acute hemorrhagic shock model. Hemorrhagic shock was induced in 24 anesthetized mechanically ventilated male rabbits by withdrawing blood to a mean arterial blood pressure (MAP) of 30 to 35 mmHg over 15 min and maintaining this state for 30 min. The animals were resuscitated by replacing the blood with equal volumes of HbV in recombinant human albumin solution (HbV/rHSA), rHSA alone, or Ringer lactated solution (RL), or with three times the withdrawn volume of RL and observed for 2 h. Fluid resuscitation restored MAP, central venous pressure, and cardiac index values, but these fell again within 2 h in rabbits treated with RL. Fluid resuscitation using HbV/rHSA immediately increased MAP and cardiac index but not systemic vascular resistance, maintained a high level of oxygen consumption, and reduced the blood glucose level, which increased after hemorrhage. Fluid resuscitation using HbV/rHSA did not disturb microoxygenation in the brain, kidneys, liver, or muscle; allowed an immediate recovery of tissue oxygenation without decreasing cardiac output or increasing systemic vascular resistance, and increased the oxygen consumption. HbV solution offers the advantages of systemic oxygenation without impairing microcirculation in the treatment of hemorrhagic shock.

DOI： 10.1097/01.shk.0000192118.68295.5d

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

Asymptomatic Brugada syndrome patients often display concealed Brugada-type electrocardiogram patterns that result in under-diagnosis of this syndrome. These patients include individuals of both genders and a wide range of ages. They are as likely as non-Brugada patients to have normal longevity or to suffer from a critical illness. Here we report a case of septic shock in which Brugada-type electrocardiogram patterns were induced by pilsicainide administration for the treatment of atrial fibrillation. This case report suggests that some drugs used in the treatment of septic shock can unmask the Brugada-type electrocardiogram pattern and induce lethal ventricular tachyarrhythmia.

DOI： 10.1213/01.ANE.0000184258.64205.9B

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Combined spinal epidural anesthesia is widely used for Caesarean section. Bolus administration of an epidural initial dose introduces the risk of drug flux from the epidural space to the subarachnoid space, and the volume effect of the initial dose may cause epidural top-up and extension of subarachnoid blockade. These problems may be avoided if the initial dose is not administered. This study investigated whether epidural continuous infusion without an initial dose (continuous group) can decrease postoperative pain as well as an epidural continuous infusion with an initial dose (initial dose group). Sixty-one patients undergoing elective Caesarean section were randomly assigned to the initial dose group or the continuous group. Twenty patients undergoing emergency Caesarean section with spinal anesthesia (spinal group) were also investigated to confirm that epidural block is effective for postoperative pain. Data in this study were obtained retrospectively from each patient. s records. Between the initial dose group and the continuous group, there was no significant difference in the number of times flurbiprofen or pentazocine were used for postoperative pain relief. However, the number of times that pentazocine was used was significantly higher in the spinal group than in other groups. This finding suggests that an epidural initial dose is unnecessary for postoperative pain relief in combined spinal epidural anesthesia for Caesarean section.

DOI： 10.1272/jnms.73.70

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Aim: The present study was designed to assess whether prophylactic use of bicarbonated Ringer's solution ameliorates metabolic acidosis in patients undergoing aortic surgery. Methods: Twenty patients undergoing elective infrarenal aortic aneurysm repair were randomly assigned to receive either bicarbonated Ringer's solution or acetated Ringer's solution. The pH, PaCO 2, and base excess (BE) were measured before surgical incision (T0), 5 min before reperfusion (T1) , 5 min after reperfusion (T2), and 30 min after reperfusion (T3). Data were compared between the two groups. Results: Both pH and BE initially showed a slight decrease in both groups during clamping. After unclamping of the aorta, an additional decrease in pH was observed in both groups (T0 to T2, and T3). There were no significant differences in pH between the groups throughout the study period. Conclusions: Aortic cross-clamping leads to the development of metabolic acidosis, with a decrease in pH and BE. The effect of administration of bicarbonated infusion fluid during elective abdominal aortic surgery had not significant compared with that of acetated Ringer's solution with respect to acid-base homeostasis.

DOI： 10.1272/jnms.72.364

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記述言語：英語   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

Aprotinin therapy is a promising strategy for reducing blood loss and blood transfusion requirements. The efficacy and safety of aprotinin in orthopedic surgery, however, remain controversial. We searched electronic databases for randomized controlled trials on the efficacy and safety of the use of aprotinin in orthopedic surgery. Thirteen trials that included a total of 506 patients who underwent major orthopedic surgery were analyzed. The pooled intraoperative and perioperative blood loss was significantly less in the aprotinin-treated patients than in the control patients (weighted mean difference [WMD] for intraoperative blood loss = -229 mL, 95% confidence interval [CI] = -367 to -91 mL, P = 0.0011; WMD for perioperative blood loss = -557 mL; 95% CI = -860 to -254 mL; P &lt; 0.0001). The pooled amounts of red blood cell (RBC) units (U) transfused intraoperatively and perioperatively were significantly less in the aprotinin-treated patients than in the control patients (WMD for intraoperative RBCU = -1.1 U; 95% CI = -1.7 to -0.4 U; P = 0.0001; WMD for perioperative RBCU= -1.1 U; 95% CI = -1.7 to -0.5 U; P &lt; 0.0001). Aprotinin was not associated with an increased incidence of deep vein thrombosis (odds ratio = 0.39; 95% CI = 0.14 to 1.05, P = 0.061). The authors conclude that aprotinin reduces the intraoperative and perioperative blood loss and allogeneic blood transfusion requirement and may not be associated with increased risk of deep vein thrombosis in the presence of pharmacological or mechanical prophylaxis in patients undergoing major orthopedic surgery.

DOI： 10.1213/01.ANE.0000180767.50529.45

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：BIOMEDICAL RESEARCH PRESS LTD  

Previous studies have suggested that cannabinoid compounds are anticonvulsants and that these compounds depress respiratory activity. However, the anticonvulsant potential of cannabinoids and their depressive effect on respiration have not been evaluated simultaneously. In the present study, we used a brainstem-spinal cord preparation model to investigate changes in inspiratory activity and the anticonvulsant effects of a cannabinoid receptor agonist, WIN55, 212-2, in bicuculline-induced convulsion. Application of 10 mu M WIN55, 212-2 caused no change in inspiratory activity (6.9 +/- 0.89 bursts/min vs. 8.0 +/- 1.3 bursts/min, not significant) and decreased bicuculline-induced seizure-like nerve activity (number of seizure-like activities in 10 min, 11 +/- 7.4 bursts vs. 1.5 +/- 1.6 bursts, P &lt; 0.01; average duration of seizure-like activity, 8.9 +/- 4.0 see vs. 4.7 +/- 2.1 see, P &lt; 0.01). Our results suggest that administration of an appropriate dose of cannabinoid receptor agonist WIN55, 212-2 has an anticonvulsant effect but does not cause respiratory depression.

DOI： 10.2220/biomedres.26.241

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記述言語：英語   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

DOI： 10.1213/01.ANE.0000173762.12938.37

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記述言語：英語   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

The objective of this study was to systematically determine the diagnostic accuracy of bedside tests for predicting difficult intubation in patients with no airway pathology. Thirty-five studies (50,760 patients) were selected from electronic databases. The overall incidence of difficult intubation was 5.8% (95% confidence interval, 4.5-7.5%). Screening tests included the Mallampati oropharyngeal classification, thyromental distance, sternomental distance, mouth opening, and Wilson risk score. Each test yielded poor to moderate sensitivity (20-62%) and moderate to fair specificity (82-97%). The most useful bedside test for prediction was found to be a combination of the Mallampati classification and thyromental distance (positive likelihood ratio, 9.9; 95% confidence interval, 3.1-31.9). Currently available screening tests for difficult intubation have only poor to moderate discriminative power when used alone. Combinations of tests add some incremental diagnostic value in comparison to the value of each test alone. The clinical value of bedside screening tests for predicting difficult intubation remains limited.

DOI： 10.1097/00000542-200508000-00027

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCIENCE BV  

Although general anesthesia is routinely used as an essential surgical procedure and its harmlessness has been evaluated and endorsed by clinical outcomes, little is known about its comprehensive influence that is not reflected in mortality and morbidity. In this paper, we have shown that inhalation anesthesia affected the expression of &lt; 1.5% of &gt; 10,000 genes, by analyzing the expression profiles for multiple organs of rats anesthetized with sevoflurane. The small number of transcripts affected by the inhalation anesthesia comprised those specific to single and common in multiple organs. The former included genes mainly associated with drug metabolism in the liver and influenced by agents such as amphetamine in the brain. The latter contained multiple circadian genes. In the brain, we failed to detect the alteration of the clock gene expression with the exception of Per2, assuming that anesthesia perturbs circadian rhythMs. Our findings provide the first assessment for the influence of inhalation anesthesia by approaches of experimental biology and genome science. (c) 2005 Elsevier B.V. All rights reserved.

DOI： 10.1016/j.gene.2005.03.022

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

In Japan, an ever-present problem in the preoperative evaluation of patients with ischemic heart disease is that although such evaluations are based on Western data, these data serve as the basis for determining perioperative risk in Japanese patients. To remedy this problem, the Cardiac Ischemia and Anesthesia Research Committee was formed in 1997 and has conducted studies of perioperative complications in noncardiac surgery in Japan. In two retrospective studies in 1997, the proportions of patients with ischemic heart disease were 3.9% and 3.1%, approximately one tenth the rates reported in Europe and the United States. The incidences of perioperative cardiac complications in patients with ischemic heart disease were 16.4% and 13.2%, not widely divergent from rates reported in Europe and the United States. To investigate the baseline characteristics involved in perioperative complications, we conducted a prospective study of 237 patients classified as having intermediate risk for,perioperative cardiac complications according to the American College of Cardiology/American Heart Association Guidelines for Perioperative Cardiovascular Evaluation for Noncardiac Surgery. We found that the prominent factor in intraoperative cardiac complications was the presence of hypertension (odds ratio = 2.911). Factors contributing to postoperative cardiac complications included those reflecting coronary lesion severity and cardiac dysfunction (history of heart failure; odds ratio = 6.884, coronary risk index grade; odds ratio 2.884, and a history of intervention; odds ratio = 4.774).

DOI： 10.1213/01.ANE.0000152009.49024.F1

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：CAMBRIDGE UNIV PRESS  

Background and objective: The exact change in circulating blood volume (BV) during general anaesthesia is still unknown because there is no standard method of evaluating BV We evaluated the changes in BV by general anaesthesia using simple and easy estimation methods.
Methods: Fourteen patients scheduled for minor surgery under general anaesthesia were enrolled. Propofol and vecuronium bromide were used for the induction of anaesthesia, and anaesthesia was maintained with sevoflurane and nitrous oxide. Haematocrit (Hct), total protein concentration (TP), as well as colloid osmotic pressure (COP) measured using a colloid osmometer, were determined before anaesthesia, and 30, 60 and 90 min after the induction of general anaesthesia. BV was calculated using Allen's formula and the changes in Hct, TP and COP. The estimated BV was compared with directly measured 1311 using indocyanine green dilution method (BVICG).
Results: Hct, TP and COP significantly decreased after the induction of anaesthesia (Hct: 42.1-39.4%; TP: 7.3-6.9 g dL(-1); COP: 23-19 mmHg). The calculated BV as well as BVICG, significantly increased after induction of anaesthesia (calculated by COP: 4.13-5.03 L; BVICG: 4.54-5.5 6 L). The change rate in BV calculated by the change of COP was larger than other calculated BVs, and was approximated to the change rate in BVICG, After emergence from anaesthesia, all values tended to return to baseline.
Conclusions: General anaesthesia increases BV The value of BV calculated from the change in COP was most changeable.

DOI： 10.1017/S0265021505000438

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Endogenous carbon monoxide (CO) production has been recently observed to be an index of the inflammatory response, reflecting various insults in critically ill patients. Major surgery is supposed to modulate the production of CO by transcriptional regulation of heme oxygenase (HO). CO is easy to measure as carboxyhemoglobin (CO-Hb) by spectrophotometry
however, whether CO-Hb can be used as an index reflecting surgical insults is unknown. We investigated changes in CO generation during coronary artery bypass graft by measuring CO-Hb concentrations and the expression of HO in circulating blood as well as the expressions of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β). The expression ratios of heme oxygenase-1 (HO-1), TNF-α, and IL-1β significantly increased after surgery, and these values correlated significantly with one another. CO-Hb concentrations significantly increased after surgery
however, many of those values during artificial ventilation with high inspired oxygen fraction were within normal limits. Furthermore, changes in CO-Hb concentrations were small when preoperative values were high. On the whole, CO-Hb concentrations significantly but weakly correlated with the expression ratios of the inflammatory mediators. However, they did not correlate in the patients who showed higher preoperative CO-Hb concentrations. These data indicate that CO-Hb concentrations can, in general, reflect the inflammatory response induced by surgical insult
however, CO-Hb measurement may not be a useful form of clinical monitoring because of the limited degree of changes, the variation of baseline values, and the necessity for the management under fixed conditions.

DOI： 10.1272/jnms.72.19

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Purpose: Although general anesthetics may decrease neuronal excitation, their detailed effects on spontaneous excitatory postsynaptic currents (EPSCs) remain controversial. We investigated and compared the effects of halothane on N -methyl-D-asparate (NMDA) and non-NMDA receptor-mediated postsynaptic currents. Methods: Spontaneous synaptic currents were recorded by the patch clamp technique in cultured rat cortical neurons. They were isolated by specific pharmacological blocking agents and their electrophysiologic properties were examined. Results: The frequency of NMDA EPSCs was preferentially decreased as compared with that of non-NMDA EPSCs at halothane 1.2 mM. The total net charge of EPSCs mediated by NMDA and non-NMDA receptors was depressed to 56% ± 6% (mean ± SD) and 71% ± 7% of control by halothane 0.6 mM, and to 11% ± 9% and 59% ± 11% of control by halothane 1.2 mM, respectively. Conclusion: These results show that halothane causes decrease of excitatory synaptic activity, with NMDA EPSCs being more sensitive than non-NMDA EPSCs. © JSA 2005.

DOI： 10.1007/s00540-004-0285-x

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCIENCE INC  

Study Objective: To assess the hemodynamic, renal, and endocrine effects of small continuous doses of atrial natriuretic peptide (ANP) in patients anesthetized with sevoflurane for gastrectomy.
Design: Prospective randomized study.
Setting: Operating room and wards of a university hospital.
Patients: 20 ASA physical status I and II patients scheduled for gastrectomy.
Intervention: Atrial natriuretic peptide (0.05 mu g/kg/min; ANP group, n = 10) or saline (control group, n = 10) was infused continuously for 2 hours beginning at the start of the operation.
Measurements: Plasma concentrations of ANP, brain natriuretic peptide, cortisol, angiotensin II, and aldosterone; plasma renin activity; serum and urinary sodium, potassium, and chloride; and urinar output.
Main Results: The ANP group showed much greater urine volume and sodium, potassium, and chloride excretion than the control group, although the ANP group had a lower arterial blood pressure. The infusion did not affect surgery-induced increases in hormones. No patients experienced excessive hypotension, bradycardia, or other perioperative complications.
Conclusions: Continuous intravenous infusion of ANP at 0.05 mu g/kg/min during gastrectomy was associated with greater water and electrolyte excretion unaccompanied by changes in potentially interacting hormones. Low-dose infusion may be particularly safe and useful for controlling water and electrolyte metabolism intraoperatively. (c) 2005 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.jclinane.2004.03.006

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記述言語：英語   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

DOI： 10.1213/01.ANE.0000140814.28118.6F

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：BLACKWELL PUBLISHING ASIA  

Maintenance electroconvulsive therapy (mECT) is an outpatient procedure that requires further consideration in terms of management of ambulatory anesthesia. Although many adjunctive drugs for stabilizing hemodynamic changes during ECT have been reported, side-effects of these drugs may delay recovery and discharge from hospital. The effects of landiolol, a novel ultra-short-acting beta-adrenergic blocker, have been measured on seizure duration, hemodynamic changes, recovery from anesthesia, and cognitive function during mECT under propofol anesthesia. A total of 10 patients with depression in the remission phase, were studied in a randomized, double-blind, placebo-controlled, crossover manner. Administration of 0.1 mg/kg of landiolol immediately before anesthesia significantly blunted the increase in heart rate and blood pressure during convulsions compared with placebo; landiolol was not associated with excessive hypotension or bradycardia. Landiolol did not affect seizure duration, recovery from anesthesia, or cognitive function before or after ECT. These results suggest that landiolol can be used effectively and safely during mECT.

DOI： 10.1111/j.1440-1819.2004.01322.x

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

The prostaglandin (PG) E-2 receptor subtype EP4 has been found to mediate regulation of inflammatory cytokines in macrophages and neutrophils in vitro by PGE(2). Yet the role of EP4 receptors in endotoxin shock in vivo and whether EP4 activation is a beneficial treatment are not clear. We tested the effect of an EP4 agonist on hemodynamic changes and production of inflammatory cytokines in a rat endotoxin-induced shock model. In rats under pentobarbital anesthesia, lipopolysaccharide (LPS) was injected, and an EP4 agonist (ONO-AE1-329) was administered at one of three concentrations (1, 3, or 10 mug/kg bolus i.v. hourly). Mean arterial pressure (MAP) was monitored throughout the experiment, and pressor responses to norepinephrine were determined 6 h after LPS injection. Serum tumor necrosis factor (TNF)-alpha and serum interleukin (IL)-6 were measured 1 h and 6 h after LPS injection. Venous nitrosyl hemoglobin (NO-Hb) concentration was measured by electron spin resonance. Expression of mRNAs encoding TNF-alpha and inducible nitric oxide synthase (NOS) in the left ventricle and descending aorta was determined with a real-time reverse transcription polymerase chain reaction. As time progressed, LPS significantly depressed MAP and decreased reactivity to norepinephrine. Infusion of higher doses of the EP4 agonist at 3 and 10 mug/kg/h attenuated LPS-induced hypotension and hyporeactivity to norepinephrine. LPS significantly increased serum concentrations of TNF-alpha and IL-6, and higher doses of EP4 agonist significantly attenuated these increases. Left ventricular and aortic expression of mRNAs encoding TNF-alpha and NOS was increased by LPS; again, EP4 agonist at higher doses attenuated the increases. LPS-induced production of inflammatory mediators and cardiovascular depression were attenuated by EP4 agonist administration in an in vivo endotoxin shock model. Anti-inflammatory effects thus would be involved in protection by EP4 agonist against cardiovascular depression in endotoxin shock.

DOI： 10.1097/01.shk.0000129338.99410.5d

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：BIOMEDICAL RESEARCH PRESS LTD  

Both the production of nitric oxide (NO) through the inducible NO synthase (iNOS) pathway and the production of carbon monoxide (CO) through the inducible heme oxygenase (HO-1) pathway have been implicated as major contributors in the process of many pathological inflammatory conditions, however, the exact role of CO and the interaction between NO and CO production systems during inflammatory cytokine-induced myocardial depression are not yet clarified. Using the isolated rat working heart model, the effects of iNOS inhibitor (L-canavanine) and HO inhibitor (zinc protoporphyrin) on inflammatory cytokines (tumor necrosis factor-alpha and interleukin-1 beta)-induced cardiac depression as well as the changes in gene expression of NOS and HO were evaluated. Administration of cytokines significantly increased iNOS and HO-1 mRNA expression in the left ventricle and depressed cardiac contraction. L-canavanine attenuated cytokine-induced cardiac depression and increase in HO-1 mRNA expression. Zinc protoporphyrin did not worsen cytokine-induced cardiac depression and increased iNOS mRNA expression. These data suggest that NOS/NO pathway system and HO/CO pathway system are interrelated at the gene expression levels even when those systems are highly promoted. However, the interaction of both systems on cardiac contractility did not make clear and other factors are speculated to be important under excessive production of those gaseous molecules.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Japanese Association for Thoracic Surgery  

Erythromelalgia is known as a rare syndrome of unknown etiology, characterized by redness with burning pain, edema associated with increased skin temperature in the upper and/or lower extremities. Various treatments such as drug therapies and sympathetic blockade were reported. We report two cases including a 57-year-old woman and a 64-year-old woman, showing the successful clinical outcome by bilateral thoracoscopic sympathectomy.

DOI： 10.1007/s11748-004-0003-5

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Purpose. Activation of purinoceptors may improve neuropathic pain. Accordingly, the effects of systemic ATP infusion were assessed in patients with postherpetic neuralgia (PHN). Methods. Eight patients with PHN lasting over 3 months were enrolled. Initially, patients received the vehicle (20% dextrose) or ATP (at a dose of 1 mg·kg-1 in 20% dextrose) infused intravenously for 60 min on two separate occasions in a single-blinded manner. The levels of spontaneous continuous pain, paroxysmal pain, and tactile allodynia were assessed by a visual analogue scale (VAS), and tactile hypesthesia was assessed by Semmes-Weinstein monofilament before and after infusion. Subsequently, the eight patients received an ATP infusion (1 mg·kg-1 in 20% dextrose) once a week for 5-12 weeks in an open-label manner, and changes in the above parameters were assessed. Results. In the initial study, VAS for spontaneous continuous pain and tactile allodynia decreased significantly with ATP infusion but not with placebo infusion. After repeated ATP infusions for 5-12 weeks, the median VAS for spontaneous continuous pain, paroxysmal pain, and tactile allodynia decreased significantly from 32.1 to 13.0, from 46.9 to 17.5, and from 49.5 to 15.6 respectively. However tactile hypesthesia did not improve significantly. Conclusion. This study demonstrated that repetitive intravenous ATP infusion could improve spontaneous continuous pain and paroxysmal pain, as well as improving tactile allodynia, but did not influence tactile hypesthesia. © JSA 2004.

DOI： 10.1007/s00540-004-0240-x

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DOI： 10.1272/jnms.70.436

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：BLACKWELL MUNKSGAARD  

Background: Cardiogenic pulmonary edema is a frequent cause of respiratory failure. We investigated whether milrinone improved lung compliance.
Methods: We selected 10 patients with respiratory failure due to severe cardiogenic pulmonary edema to receive mechanical ventilation. Patients were administered a bolus injection of milrinone (50 mug kg(-1)) over 10 min, followed by continuous intravenous infusion (0.5 mug kg(-1) min(-1)). Lung compliance, blood gas values, hemodynamic parameters, and sample plasma milrinone levels were assessed over 120 min after the onset of the continuous infusion of milrinone.
Results: Ten min following milrinone infusion, dynamic compliance (Cdyn) and static compliance (Cst) increased from 37 +/- 12 to 42 +/-12 ml cmH(2) O-1 and from 40 +/-13 to 45 +/-12 ml cmH(2) O-1 , respectively (P &lt; 0.01). Plasma milrinone levels reached a therapeutic level for vasodilator and positive inotropic effect at 10 min after milrinone infusion. A significant decrease in mean pulmonary artery pressure and pulmonary artery wedge pressure occurred simultaneously with an increase in respiratory system compliance. However, an increase in cardiac index was observed later than these changes. There were significant correlations between the mean pulmonary artery pressure and Cdyn (r = -0.39, P &lt; 0.01) and Cst (r = -0.38, P &lt; 0.01).
Conclusions: Milrinone-induced improvement in lung compliance along with an improvement of hemodynamics was found together with an inverse relationship between compliance and mean pulmonary artery pressure.

DOI： 10.1034/j.1399-6576.2003.00124.x

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：BIOMEDICAL RESEARCH PRESS LTD  

The aims of the study were to evaluate whether inhalation anesthetics have the same mechanisms of negative inotropic action, and to compare the relationship between the calcium homeostasis and cardiac depression for each anesthetic. The effects of inhalation anesthetics on left ventricular contraction, calcium content of the sarcoplasmic reticulum (SR; as measured by caffeine-induced calcium release), and calcium content of the left ventricular muscle (as measured by atomic absorption spectroscopy) were evaluated in the isolated perfused rat heart. Inhalation anesthetics (i.e., halothane, enflurane, isoflurane, and sevoflurane) reduced both left ventricular contraction and calcium content of the SR. For all four drugs, there was a relationship between the negative inotropic effect and the decrease in calcium content of the SR. Sevoflurane maintained the calcium content of both the SR and the left ventricular muscle at a significantly higher level as compared with other anesthetics. These data suggest that, although inhalation anesthetics increase the calcium permeability of cardiac SR, their mechanisms of myocardial contractile depression are different.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Medical Association of Nippon Medical School  

Eleven cases of injury of the superficial radial nerve on the wrist joint, caused by intravenous injection of a needle, Paralysis occurred immediately after injection of a needle into the cephalic vein of the wrist joint, which was immediately recognized by the patients themselves. Six patients who had only sensory disturbance without causalgia were subjected to follow-up observation:5 patients with causalgia were administered with steroid infiltration injection 3 to 5 times. Of the latter 5 patients, one patient underwent surgery because the steroid infiltration injection showed no effects. Four patients (36.4%) completely recovered within three months, while 7 patients (63.6%) continued to show nervous symptoms. We concluded that intravenous injection of a needle should be performed at the wrist joint only when it is inevitable.

DOI： 10.1272/jnms.70.355

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Medical Association of Nippon Medical School  

Proinflammatory cytokines have been implicated in mediating respiratory failure associated with major surgery. We investigated the effect of giving glucocorticoids preoperatively for the prophylaxis of surgical stress and the association of cytokine levels, such as interleukin-6 (IL-6) and interleukin-8 (IL-8), with oxygenation after esophagectomy. We studied 17 patients who underwent subtotal esophagectomy. Seven patients (steroid group) were chosen at random to be given methylprednisolone (10 mg/kg) and 10 patients (control group) to be given saline intravenously before operation. Plasma and bronchoalveolar lavage fluid (BALF) IL-8 levels in the control group were significantly higher than those in the steroid group. In both groups, plasma IL-6 levels were significantly higher than those in BALF, but in contrast, BALF IL-8 levels were significantly higher than plasma levels of IL-8 postoperatively. The PaO2/FiO2 ratio was significantly reduced in the control group. The PaO2/FiO2 ratio of the control group had significantly lower values than that of the steroid group. There was significant correlation between BALF IL-8 levels and the PaO2/FiO2 ratio postoperatively. We conclude that preoperative administration of methylprednisolone may attenuate postoperative reduction of arterial oxygen saturation by suppressing the release of cytokines.

DOI： 10.1272/jnms.70.16

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記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Medical Association of Nippon Medical School  

Erythromelalgia is a rare condition that is characterized by the triad of redness, increased temperature, and intense pain of feet or hands. This syndrome was first described in 1878, however, universal classification, precise mechanism and successful medical treatment of erythoromelalgia have not been described. We experienced 3 cases of erythomelalgia in our outpatient pain clinic that showed the different progress. One patient experienced the long-term pain complicated with neuropathic pain. The pain of other two patients was eliminated early by nerve block treatments, and they did not showed chronic pain. From the prophylactic viewpoint of chronic pain, the most considerable matter is early and certain elimination of severe pain under certain diagnosis. In this article, the mechanisms of passing into the chronic pain state as well as the efficacy of neural blockade for intractable pain such as erythromelalgia are discussed.

DOI： 10.1272/jnms.70.66

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

Low back pain is one of the most prevalent complaints in clinical medicine. Sensations from the axial skeleton and the surrounding tissues are only vaguely somatotopic and are non-specific in quality. The diagnosis of the mechanism or source of low back pain is therefore very challenging. The treatment of low back pain that recurs, persists or intensifies is also formidable, because there has been no evidence of various therapies for chronic back pain. From the prophylactic viewpoint of chronic pain, the most considerable matter is early elimination of severe pain under certain diagnosis. In this article, the mechanisms of passing into the chronic state, especially the development of neuropathic pain, and the utilities of diagnostic and therapeutic neural blockade for low back pain are discussed.

DOI： 10.1272/jnms.69.588

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：AMER MEDICAL ASSOC  

Objectives: To detect free radicals in phacoemulsification and aspiration procedures using electron-spin resonance and to observe the effect of ophthalmic viscosurgical devices (viscoelastic agents) on free radical intensity.
Methods: (1) A test tube containing BSS Plus (Alcon Laboratories, Inc, Fort Worth, Tex) with 1% of the spin-trapping agent, 5,5'-dimethyl-1-pyrroline N-oxide, without irrigation and aspiration, was exposed to ultrasound (100% for 20 seconds). A preparation of hyaluronate sodium (Healon [a cohesive agent that contains 1% hyaluronate sodium] [Pharmacia, Uppsala, Sweden] or Viscoat [a dispersive agent that contains 3% hyaluronate sodium and 4% chondroitin sulfate] [Alcon Laboratories, Inc]) was added to the solution to observe inhibitory effects. (2) To simulate a clinical procedure, an eye model with irrigation and aspiration of a combination of 1% 5,5'-dimethyl-1-pyrroline N-oxide and BSS Plus, 25 mL/min, as the irrigating solution was exposed to ultrasound (for 10, 20, or 30 seconds). Healon or Viscoat was injected into the anterior chamber. Free radicals were measured by an electron-spin resonance spectrometer.
Results: (1) A characteristic signal corresponding to hydroxyl radicals was detected. Similar inhibition by Healon and Viscoat was observed. (2) Two ophthalmic viscosurgical devices similarly suppressed the signal at 10 seconds. The inhibition by Healon ceased at 20 seconds, whereas Viscoat suppressed the signal throughout the time course.
Conclusions: Phacoemulsification produces hydroxyl radicals in the anterior chamber even with irrigation and aspiration. The effect of ophthalmic viscosurgical devices on free radicals depends on the retention of the materials within the anterior chamber. Clinical Relevance: There are complications associated with phacoemulsification.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：W B SAUNDERS CO  

Objective: To study several markers of myocardial injury in relation to aortic cross-clamping and cardiopulmonary bypass (CPB) after coronary artery bypass graft (CABG) surgery.
Design: Prospective observational study.
Setting: University hospital.
Participants: Thirty adult patients who underwent elective CABG surgery with aortic cross-clamping and CPB.
Measurements and Main Results. Serum levels of interleukin-6 (IL-6), interleukin-8 (IL-8), troponin-T (TnT), myosin light chain I (MLCl), and MB isoenzyme of creatine kinase (CK-MB), as markers of myocardial injury, were measured after induction of anesthesia for baseline values, then again at the end of surgery and on postoperative days 1, 3, and IL-6, IL-8, and CK-MB levels were significantly elevated in the early postoperative stage. TnT significantly increased from the, end of surgery to postoperative day 5. MLCl increased also but later than TnT. Aortic cross-clamping time correlated positively with peak TnT (r = 0.51, p &lt; 0.05), TnT level on postoperative day 1 (r = 0.69, p &lt; 0.01), and MLCl level on postoperative day 5 (r = 0.45, p &lt; 0.05). CPB time was correlated only with peak TnT (r = 0.47, p &lt; 0.05).
Conclusions: The increase in TnT level is strongly related to aortic cross-clamping. Copyright 2002, Elsevier Science (USA). All rights reserved.

DOI： 10.1053/jcan.2002.125150

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記述言語：英語   出版者・発行元：CANADIAN ANESTHESIOLOGISTS SOC  

DOI： 10.1007/BF03020541

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Inhibition of nitric oxide (NO) synthesis has been indicated to improve vasopressor-responsiveness and to increase blood pressure in most septic models. However, numerous adverse effects of non-selective NO synthase (NOS) inhibition have been reported, and the effect of NOS inhibition on vascular responsiveness to vasodilators has not been well studied. Using an isometric tension measurement system of vascular rings, we evaluated the effects of an inducible NOS (iNOS) inhibitor, L-canavanine (L-CAN) and a non-selective NOS inhibitor, NG-nitro-L-arginine methyl ester (L-NAME) on interleukin-1β (IL-1β)-induced vascular hyporeactivity in the four different rabbit arteries. Pretreatment of IL-1β inhibited phenylephrine (Phe)-induced vascular constriction in the carotid artery (CA, 49% of control), pulmonary artery (PA, 66%), femoral artery (FA, 71%) and in the renal artery (RA, 83%). A combination of NOS inhibitors attenuated the vascular hyporeactivity to Phe in all arteries. Pretreatment of IL-1β also inhibited acetylcholine (Ach)-induced vascular relaxation in FA, RA and CA. In PA, the rings were inversely constricted after Ach administration. The combination of IL-1β with L-CAN, but not with L-NAME, attenuated the Ach-induced vasorelaxation to the control level in all arteries. These data suggest that the selective inhibition of iNOS attenuates the direct endothelial damage induced by IL-1β in vitro.

DOI： 10.1272/jnms.69.149

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Overproduction of nitric oxide (NO) by inducible NO synthase (iNOS) plays a role in the pathophysiology of septic shock. The depression of cardiac contractility in such situations is mediated by proinflammatory cytokines, including interleukin-1β (IL-Iβ), and tumor necrosis factor-α (TNF-α). The effects of two NOS inhibitors with different isoform selectivity were compared in isolated working rat hearts. The depression of contractility by IL-1β and TNF-α was prevented by administration of a nonselective nitric oxide synthase inhibitor, N G-nitro-L-arginine methyl ester (L-NAME) or an inhibitor of inducible nitric oxide synthase, L-canavanine. In contrast, when L-NAME was administered in the absence of IL-1β and TNF-α, it depressed contractility over the 2h perfusion period by significantly reducing coronary flow. These results support current thinking that the depression of myocardial function by IL-1β and TNF-α is mediated, at least in part, by an intracardiac increase in inducible nitric oxide synthase, and that in contrast to L-NAME, the decline in coronary conductance seen in cytokine-treated is not prevented by L-canavanine hearts. L-canavanine shows selective inhibition of inducible nitric oxide synthase unlike the vasopressor action of L-NAME in cytokine-treated hearts.

DOI： 10.1272/jnms.69.13

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

Chronic constriction injury (CCI) of the sciatic nerve in rats induces persistent mechanical hyperalgesia and allodynia. CCI is widely known as a model of neuropathic pain, and many studies using this model have been reported. Recently, c-fos has been used as a neural marker of pain, and various studies have assessed the relationship between hyperalgesia and c-fos expression in the lumbar spinal cord. In this study, we examined the role of a prostaglandin E(2) receptor subtype EP(1) receptor antagonist (ONO-8711) in a rat CCI model. EP(1) receptor antagonist (EP(1)-ra) oral administration from day 8 to day 14 significantly reduced hyperalgesia and allodynia in the three pain tests on day 15. EP(1)-ra treatment from day 8 to 14 also reduced c-fos-positive cells in laminae I-II, III-IV, and V-X compared with saline treatment. A single dose of EP(1)-ra treatment on day 8 significantly reduced hyperalgesia and allodynia at 1 h and 2 h after administration, but the efficacy was not observed at 24 h. We conclude that EP(1)-ra treatment may be useful for hyperalgesia and allodynia and that EP(1) receptor mechanisms are involved in the maintenance of c-fos gene expression induced by nerve injury.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：BIOMEDICAL RESEARCH PRESS LTD  

When liver failure is induced by ischemia-reperfusion injury or sepsis, neutrophils or Kupffer cells produce reactive oxygen species (ROS), nitric oxide (NO), or peroxynitrite (ONOO-). These substances have been shown to induce cytotoxicity and apoptosis in various cells. In this study, using rat hepatocytes exposed to AAPH (free radical generator), NOC 18 (NO donor),and SIN-1 (peroxynitrite generator), we investigated which substance induced the earliest and most severe hepatocellular damage and apoptosis. Hepatocytes treated with 15 mM AAPH for 6 h showed significantly reduced viability, significantly increased apoptosis, and a significant increase of hepatocellular enzymes compared with control cells or with those exposed to I mM NOC 18 and I mM SIN-1. On the other hand, hepatocytes treated with a combination of 0.25 mM NOC 18 and 15 mM AAPH showed significantly increased cell viability, significantly reduced apoptosis, and significantly lower levels of hepatocellular enzymes compared with cells exposed to 15 mM AAPH alone. These results indicate that free radicals may play a role in inducing hepatocyte damage and apoptosis in the early phase of acute liver failure, while low concentrations of NO have a cytoprotective effect against hepatocyte damage by free radicals.

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The adenosine triphosphate-dependent potassium (KATP) channel has been proposed to play an important role in the cardioprotective effect of isoflurane (ISO). However, the question of whether the KATP channel, sarcolemmal or mitochondrial is the main contributor to the effect has not been clarified. The major aim of the present study was to determine whether or not the mitochondrial potassium channel was a site of action for ISO. Whether there was an acute "memory phase", in which drugs were not detected in the tissues, but the protective effect still remained in the ischemic preconditioning (IP)-like effect of ISO was also investigated. Dangling participle isolated rat hearts, a 20-min normothermic nonperfused phase was maintained to produce a global ischemia. Under these ischemic conditions, the effects of ISO, sodium 5-hydroxydecanoate (5 HD: a selective mitochondrial KATP channel antagonist), and ISO combined with 5 HD on cardiac performance were examined. To all these four groups, (non-treated group, ISO group, 5 HD group and ISO plus 5 HD group, n=6 each) drugs were given for 30 min. After 10 min of drug-free perfusion (pre-ischemia restabilization period), 20 min of ischemia followed. Then the cardiac performance and the creatine kinase (CK) release during the reperfusion period were tested. In the non treated group and 5 HD group, cardiac performance was stable during the treated period and pre-ischemia the restabilization period. In the ISO group and ISO plus 5 HD group, heart rate (HR), left ventricular (LV) systolic pressure, and LV maximum rate of development of tension (dP/dtMax) during the drug-treated period became gradually and linearly worse. However, these values were the same as in the non-treated group and 5 HD group at the end of the pre-ischemia restabilization period. So 5 HD itself had no hemodynamic effect
nor did it have any influence on the actions of ISO. At the end of the pre-ischemia restabilization period, the significant hemodynamic differences among the groups diminished and ISO was not detected in the solution. In the post-reperfusion period, except for the ISO group, (non treated group, 5 HD group and ISO plus 5 HD group) cardiac performances were drastically decreased. ISO significantly ameliorated the dysfunction of cardiac output, LV systolic pressure and LV+dP/dtMax. The CK level in the coronary effluent during reperfusion was also significantly reduced by ISO. 5 HD completely inhibited these cardiac effects of ISO. Activation of the adenosine triphosphate sensitive mitochondrial potassium channel is involved in the cardioprotective effect of ISO, and the action of this agent has an acute "memory phase" like ischemic preconditioning.

DOI： 10.1272/jnms.68.238

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：W B SAUNDERS CO  

Objectives: To determine whether and to what extent coronary artery bypass graft (CABG) surgery without extracorporeal circulation is associated with cardiac troponin T (TnT) release.
Design: Prospective study.
Setting: A single university hospital.
Participants: Twenty-three patients scheduled for minimally invasive CABG surgery. Sixteen patients received one coronary anastomosis, and seven received two.
Interventions: TnT and creatine kinase-MB (CK-MB) levels were determined immediately before induction of anesthesia (baseline) and at 0, 12, and 24 hours after surgery. Hemodynamic measurements were made, and 5-lead electrocardiograms with continuous automated ST-segment trends were analyzed.
Measurements and Main Results: All patients had a good cardiac outcome. Median cumulative coronary artery occlusion time was 27 minutes (range, 10 to 49 minutes). TnT levels were undetectable in 91.3% of patients at baseline when a detection limit of 0.01 ng/mL was employed. TnT and CK-NIB showed significant elevations at 12 and 24 hours versus baseline. Postoperatively, TnT was detectable in 91.3% of patients, and 17.4% suffered minor myocardial damage, as evidenced by an abnormal increase in TnT greater than 0.2 ng/ml, excluding those exhibiting myocardial infarction. ST segment changes developed in seven patients, persisting for 13.0 minutes (range, 9.5 to 15.8 minutes) and disappearing immediately after coronary artery clamp release. There were no significant correlations between cumulative coronary occlusion time and peak TnT or CK-MB levels.
Conclusions:TnT was detected after surgery in most patients, and significant TnT levels indicative of myocardial injury (&gt;0.2 ng/mL) were detected in only 17% of patients, probably as a result of brief periods of coronary artery occlusion. Copyright (C) 2000 by W.B. Saunders Company.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：KLUWER ACADEMIC PUBL  

Objective. Myocardial ischemia is a risk factor during off-pump coronary artery bypass procedures. The development of new regional wall motion abnormalities assessed by transesophageal echocardiography (TEE) is a very sensitive sign of myocardial ischemia. To facilitate anastomosis, the epicardial area of the anastomosis site is often immobilized by a "stabilizer." This study was designed to investigate whether cardiac wall stabilization with an epicardial stabilizer could affect the interpretation of wall motion during coronary anastomosis without cardiopulmonary bypass. Methods. The TEE videotapes of 15 adult patients were investigated. Left ventricular (LV) transgastric short and long axis views were divided according to a modified 16-segment method. LV wall motion was scored using a 5-grade scale by two independent blinded investigators during pre-occlusion, occlusion, and reperfusion of anastomosed coronary arteries. The wall motion scores of a stabilized segment combined with two adjacent segments were compared with those of non-stabilized segments. Interobserver agreement was assessed using the weighted kappa statistic. Results. A total of 216 segments were analyzed by two investigators. The interobserver kappa coefficient in pre-occlusion and reperfusion periods was 0.87, 0.87 and 0.86, 0.87, respectively, indicating high agreements without stabilizer. During the occlusion period in stabilized and non-stabilized segments, it was 0.59 and 0.76, respectively, showing significantly less reproducibility in the presence of stabilizer. Conclusion. Cardiac wall stabilization affects the reproducibility in the interpretation of regional wall motion during off-pump coronary artery bypass surgery. Caution should be used when monitoring for myocardial ischemia using TEE during coronary artery bypass surgery with epicardial stabilizer.

DOI： 10.1023/A:1009976130084

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：BLACKWELL SCIENCE ASIA  

The effects of different doses of propofol on post-electroconvulsive therapy (ECT) cognitive recovery were evaluated together with the effects on seizure duration and hemodynamic changes during ECT in 15 depressive patients. Propofol attenuated the increase in arterial blood pressure and heart rate in a dose-dependent manner compared with thiamylal. Propofol showed a clinically significant anticonvulsant effect during ECT in a dose-dependent manner. There were no significant differences among the four different induction groups in the mean recovery time from anesthesia, however, a low dose of propofol suppressed the early recovery of cognitive function. For early cognitive recovery after ECT, a deep anesthetic level is necessary when the traditional ECT apparatus is used which produces sine curve wave stimuli.

DOI： 10.1046/j.1440-1819.1999.00621.x

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

In five depressive patients associated with chronic pain, the efficacy of electroconvulsive therapy (ECT) for pain relief was evaluated retrospectively. In all of the patients treatment with tricyclic antidepressant medication was not successful, but ECT alleviated or diminished the chronic pain associated with depression. It seems that ECT as a treatment for chronic pain in patients with depression should be taken into consideration in cases in which other treatments have failed.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Neuroleptic malignant syndrome (NMS) is the most serious side effect produced by the administration of antipsychotic drugs. NMS shares many clinical similarities with malignant hyperthermia (MH), but the etiology of NMS and the relation between NMS and MH remain unknown. Anesthetic regimens for patients with NMS are not well established. We gave repeated anesthesia to a patient with a history of NMS undergoing electroconvulsive therapy for the treatment of depression. Propofol and vecuronium were used in twelve consecutive ECT sessions without complications. In this case report, we describe the safe and satisfactory repeated use of propofol in a patient with a history of NMS, and outline NMS and its questionable relation to MH.

DOI： 10.1272/jnms.66.262

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：W B SAUNDERS CO  

Objectives: To evaluate the effects of negative-pressure ventilation (NPV) on hemodynamics using the Hayek oscillator (Breasy Medical Equipment, London, UK) and to determine whether the oscillation frequency can modify the hemodynamics, assessed by transesophageal echocardiography (TEE).
Design: A prospective study.
Setting: A university hospital.
Participants: Eleven American Society of Anesthesiologists class I patients undergoing orolaryngeal surgery.
Interventions: The ultrasound probe was inserted under general anesthesia. After baseline measurements were determined during spontaneous breathing, the frequency was changed from 30 to 60 to 120 cycles/min, consecutively. The left ventricular end-diastolic area (LVEDA), end-systolic area (LVESA), fractional area change (LVFAC), and end-systolic wall stress (ESWS) were determined. The velocities of the pulmonary artery (PA) flow, pulmonary venous (PV) flow, and transmitral flow were measured by pulsed Doppler techniques.
Measurements and Main Results: PaO2 increased and PaCO2 decreased significantly. NPV caused a significant increase in the LVEDA, whereas it did not significantly change the PA velocity. ESWS, an index of afterload, remained unchanged.
Conclusion:The authors conclude that NPV using the Hayek oscillator induces an increase in the LVEDA without any changes in PA velocity, suggesting increased transmural pressure rather than increased preload, and that the three different frequencies do not modify the effects on the hemodynamics. Copyright (C) 1998 by W.B. Saunders Company.

DOI： 10.1016/S1053-0770(98)90095-7

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：BLACKWELL SCIENCE  

Cardiogenic pulmonary edema is a frequent cause of reparatory failure. We investigated the effects of nasal continuous positive airway pressure (CPAP) in patients with severe pulmonary edema associated with acute myocardial infarction. Twenty-nine consecutive patients were divided into 3 groups: firstly, 7 intubated patients who received mechanical ventilation at study entry comprised the intubation group. The rest of the patients were randomly assigned to either of the following 2 groups: 11 patients who received oxygen plus CPAP delivered by a nasal mask (CPAP group), and 11 patients who received oxygen only via face mask (oxygen group). All patients in the intubation group had cardiogenic shock. Two patients (18%) in the CPAP group and 8 patients (73%) in the oxygen group required mechanical ventilation with endotracheal intubation (p=0.03). The hospital mortality rate in the CPAP group (9%) was significantly lower than the oxygen group (64%, p=0.02). The pulmonary artery wedge pressure and heart rate were significantly lower in the CPAP group than in the oxygen group 24 h after study entry (p&lt;0.05 and p&lt;0.01). The mean pulmonary artery pressure 48 h after study entry was 18+/-5 mmHg in the CPAP group and 25+/-8 mmHg in the oxygen group (p&lt;0.05). The PaO2/FiO2 ratio increased in the intubation group (168+/-69 to 240+/-57, p&lt;0.05) and the CPAP group (137+/-17 to 253+/-67, p&lt;0.01) 24 h after study entry. Arterial plasma endothelin-l concentrations decreased significantly earlier in the CPAP group than in the oxygen group (p&lt;0.05). In patients without cardiogenic shock, nasal CPAP lead to an early improvement in oxygenation and hemodynamics, and decreased the mortality rate. Early and active respiratory management is recommended in patients with pulmonary edema associated with acute myocardial infarction.

DOI： 10.1253/jcj.62.553

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記述言語：英語   出版者・発行元：The Medical Association of Nippon Medical School  

The purpose of this study was to evaluate the efficacy of external high-frequency oscillation (EHFO) in patients with hypercapnia following upper abdominal surgery. Seven patients were ventilated with EHFO for 2 hr at 60 oscillations/min, with cuirass pressures of 36 cm H₂O (-26 to +10), and an inspiratory to expiratory ratio of 1 : 1. Blood gases and cardiac functional parameters were examined during the 2 hr on EHFO. Pulmonary functional parameters were analyzed prior to the institution and after the termination of EHFO. PaCO₂ significantly decreased from 61±8 mmHg to 48±7 mmHg after 10 min on EHFO (p<0.01). PaO₂ significantly increased from 74±10 mmHg to 95±26 mmHg after 1 hr on EHFO (p<0.01). The heart rate decreased significantly from 108±27 beats/min to 101±24 beats/min after 30 min on EHFO (p<0.05). The FEV, and FVC significantly increased from 1.09±0.54 L to 1.50 ± 0.46 L (p<0.01) and from 1.90±0.74 L to 2.18±0.60 L (p<0.05), respectively. The other parameters of lung function also significantly improved after the termination of EHFO. The significant changes in all of the pulmonary functional parameters continued for 1 hr after the termination of EHFO. EHFO is an effective method of gas exchange which is associated with earlier return to preoperative lung function. (J Nippon Med Sch 1997; 64:440-445)

DOI： 10.1272/jnms1923.64.440

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER VERLAG  

Objective: To investigate the clinical effectiveness and safety of ONO-1101, a new ultrashort-acting (half-life 3-4 min), cardioselective beta-adrenoceptor blocker in attenuating the cardiovascular responses to endotracheal intubation in a dose-finding open study.
Methods: Laryngoscopy and tracheal intubation were performed after induction of anaesthesia with thiamylal, followed by administration of succinylcholine, and saline or ONO-1101 0.1, 0.25 or 0.5 mg . kg(-1) in 53 patients. Heart rate and blood pressure were continuously recorded beginning prior to administration until 5 min after administration of the drug, and the rate-pressure product was calculated.
Results: ONO-1101 was found to significantly blunt the increase in heart rate throughout the study. Administration of ONO-1101 0.25 or 0.5 mg . kg(-1) decreased the incidence of tachycardia. However, these doses were not sufficient to suppress the increase in systolic blood pressure, although the maximal value in the ONO-1101 0.5 mg . kg(-1) group was reduced. Rate-pressure product increased significantly after intubation in all groups, but the increase was suppressed in the ONO-1101 0.25 and 0.5 mg . kg(-1) groups as compared with the saline group. Bradycardia was not observed in any patient, although hypotension might be caused by administration of ONO-1101 0.5 mg . kg(-1).
Conclusion: ONO-1101, especially at a dose of 0.25 mg . kg(-1), due to its beta-adrenoceptor blockade and ultrashort action, was shown to be effective and well tolerated by patients in this study, when used to attenuate the cardiovascular responses to laryngoscopy and endotracheal intubation.

DOI： 10.1007/s002280050232

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記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Medical Association of Nippon Medical School  

It is well known that both local and volatile anesthetics depress myocardial functions. This study was performed to evaluate the combined effects of commonly utilized local anesthetics (bupivacaine, mepivacaine, and lidocaine) and a volatile anesthetic (isoflurane) on heart rate and myocardial contractility in an isolated rat working heart preparation using each local anesthetic at 0 to 3 x 10-4 (mol/L) with or without 1 MAC (minimum alveolar concentration) of isoflurane. The three local anesthetics depressed the heart rate and myocardial contractility dose-dependently. Bupivacaine depressed the heart rate more than the other two local anesthetics. One MAC isoflurane showed significant negative inotropic effects, and accelerated the effects of the local anesthetics. By using isobolographic analysis, we concluded that the combined effect of isoflurane and bupivacaine on myocardial negative inotropism was synergistic, while the effects of isoflurane and mepivacaine or lidocaine were additive.

DOI： 10.1272/jnms1923.64.292

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILLIAMS & WILKINS  

Using a superfine fiberscope with an outer diameter of 0.75 mm, the effect of repeated injections through a single epidural catheter on the epidural space was examined in 18 patients. The subjects were divided into a control group of 10 patients who had not previously received epidural anesthesia (EA) and an EA group of 8 patients who had received repeated EA with 4-6 mL 0.25% bupivacaine through an epidural catheter, two to three times per day for 7-14 days. The epidural space was observed through a fiberscope passed through a 17-gauge Tuohy needle. The epidural space was occupied by large masses of fat, and the blood vessels and connective tissue were confirmed. Adverse reactions in the epidural tissue, such as hemorrhage or congestion with engorgement, were observed in four patients in the EA group. Five patients in the EA group experienced pain when the fiberscope was inserted into the epidural space. These investigations show that continuous EA might be followed by a high incidence of nonspecific epidural changes. Superfine fiberscope may be useful in the detection or diagnosis of local epidural reaction.

DOI： 10.1097/00000539-199601000-00015

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCIENCE BV  

L-Canavanine, a selective inhibitor of inducible nitric oxide (NO) synthase, has beneficial effects on the circulatory failure of rats with endotoxin shock. To investigate the direct relationship between these beneficial effects and the inhibition of the formation of NO in response to L-canavanine in endotoxin shock in the rat, we detected changes in venous nitrosyl-hemoglobin (NO-hemoglobin) levels using an electron spin resonance (ESR) assay. Anaesthetized rats were injected with lipopolysaccharide (10 mg/kg i.v.). 1 h after the lipopolysaccharide injection, the rats were divided into four groups: a lipopolysaccharide group receiving 0.3 ml of saline hourly, an L-canavanine 10 or an L-canavanine 20 group receiving L-canavanine 10 or 20 mg/kg i.v. hourly, respectively, and an L-NAME group receiving N-G-nitro-L-arginine methyl ester (L-NAME) 15 mg/kg followed by 10 mg/kg i.v. hourly. A sham group received saline instead of lipopolysaccharide, and an L-canavanine group received L-canavanine 20 mg/kg i.v. hourly, 1 h after the saline injection. At 5 h after the lipopolysaccharide or saline injection, presser responses to noradrenaline (1 mu g/kg i.v.) were obtained. In the lipopolysaccharide group, lipopolysaccharide caused a progressive decrease in mean arterial pressure and an impairment of presser responsiveness to noradrenaline. Administration of L-canavanine or L-NAME attenuated the endotoxin-induced hypotension and vascular hyporeactivity to noradrenaline. L-Canavanine did not alter mean arterial pressure and the presser response to noradrenaline in the L-canavanine group. The endotoxin-induced increases in venous levels of NO-hemoglobin were significantly inhibited by L-canavanine or L-NAME. These data indicate that the beneficial hemodynamic effects of L-canavanine are associated with inhibition of the enhanced formation of NO by inducible NO synthase in a rat model of endotoxin shock. L-Canavanine is a potential agent in the treatment of endotoxin shock.

DOI： 10.1016/0014-2999(95)00593-5

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

A 65-yr-old male with severe scar pain on his right lower abdomen underwent selective nerve block through epidural space using a superfine fiberscope. A12-gauge Tuohy needle (internal diameter 2.2 mm) was inserted at the intervertebral space of Th12-L1. The fiberscope (external diameter 1.1 mm) was introduced through the needle and the epidural space was observed. When the dura mater of Th12 nerve root level was seen, the patient had pain on the scar area. Then 2 % lidocaine 1.5 ml and 60 % meglmine sodium amidotrizoate 1.5 ml were slowly injected. Soon after injection of anesthetic, analgesia area (Th11-L1) was obtained, and Th12 nerve root was identified by X-ray. Epidural blockade using a superfine fiberscope seems to be one of the useful and reliable methods for the selective nerve blockade.

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

Forty-one patients were treated with epidural neurolysis using 50 % ethyl alcohol 2 ml. Thirty eight patients were suffering from cancer pain and three patients were complaining of chronic benign pain. Alcohol block was repeated 2.3 times (mean) in the same patient. Thirty patients were followed after the treatment. Forty-seven percent of the patients reported 70 % or greater pain relief and 20 % of the patients reported about 50 % pain relief. Duration of pain relief was from 9 days to 203 days with a mean duration of 54 days. Adverse effects were reported 43 % of the patients. There is no miserable adverse effect. Adverse effect reported most was pain with epidural injection of drugs after the alcohol block had been performed.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Springer-Verlag  

The visual outcome in 308 patients treated for retinal vessel obstruction was examined retrospectively and the effectiveness of each treatment was evaluated using stepwise multiple linear regression analysis and the chi-square test. Visual acuity was used as the parameter for assessing treatment effectiveness and the variables investigated included treatment factors [stellate ganglion block (SGB), urokinase administration, and prostaglandin administration] and patient factors (age, duration of visual impairment before treatment, hypertension, and diabetes mellitus). SGB treatment, the duration of visual impairment, and the presence of diabetes mellitus were significantly correlated with the visual prognosis following treatment. These results support the current hypothesis that SGB is a viable treatment for patients with obstructive disease of the retinal vessels. © 1994 JSA.

DOI： 10.1007/BF02482752

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1007/s0054030070248

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The efficacy of dihydropyridine derivatives in inhibiting lipid peroxidation was studied using modified Buege and Aust's method. The method first involves keeping a decapitated rat head at 37°C for 30 min in order to induce global ischemia. Then, the cortex is removed and homogenized, and the homogenate is subsequently exposed to air for 30 min for reoxygenation. Finally, the amount of thiobarbituric acid-reactive substances (TBAR) is measured. With this method, nisoldipine, nimodipine, nitrendipine, nifedipine and nicardipine were all shown to have an antioxidant activity that correlated with their lipophilicity, which was determined by their octanol/water partition coefficients. © 1993 Japanese Society of Anesthesiologists.

DOI： 10.1007/s0054030070193

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

We compared the effect of hypertonic salt solution (7.2 %, HS) with that of normal saline (NS) and lactated Ringer's solution (LR) for the treatment of hemorrhagic shock. We monitored hemodynamic parameters, thoracic duct lymph flow, and tissue oxygen tension over 3 hours after hemorrhage. Twenty- seven anesthetized mongrel dogs (0.5 % halothane) were bled to an aortic pressure of 60 mmHg for 90 min following 40 mmHg for 30 min and then they were resuscitated with each solution. In NS group, the volume transfused was twice the bled volume, and in other two groups, each solution was transfused providing equal amounts of sodium as NS group. We found that hemodynamics were restored in HS group as well as in other two groups. On the other hand, thoracic duct lymph flow and tissue oxygen tension of renal cortex and liver increased significantly over other two groups. We conclude that small volume resuscitation with 7.2 % NaCl may be effective in the initial treatment of hemorrhagic shock from the view of tissue circulation in vital organs.

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Free radical (FR) formation in the rat intestinal lumen was measured using the spin-trapping technique and electron paramagnetic resonance spectroscopy. Intestinal ischemia was produced by occluding the celiac and the superior mesenteric arteries for 30 min followed by reperfusion. The lumen was filled with a solution of PBN (N-tertbutyl-α-phenyl-nitrone) and the intestine was squeezed to enhance the interaction between the PBN solution and the intestinal mucosal cells. Free radicals were produced upon reperfusion, with peaks at 5 and 90 min. Post-ischemic treatment with superoxide dismutase (20 mg·kg -1) inhibited the increase of FR production during the second peak by 36%. In a single study in a group of leucocytopenic rats (WBC&lt
1500/mm3 ), the increase of FR production during the second peak was decreased by 80%. However, these treatments did not inhibit the FR production during the first peak in either group. In contrast, pretreatment with allopurinol (40 and 100 mg·kg -1 injection at 24 and 3 hours before ischemia, respectively) inhibited the FR production during the first peak by 16%, but did not inhibit during the second peak. The changes in lipid peroxidation in the intestinal mucosa, specific gravity of the intestine and in the hematocrit were correlated to the FR production in the second peak. These results suggest that a major cause of tissue injury after reperfusion in the ischemic intestine may largely be produced by neutrophils. © 1992 Japanese Society of Anesthesiologists.

DOI： 10.1007/s0054020060414

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：CHURCHILL LIVINGSTONE  

The inhibition of lipid peroxidation by oligomeric derivatives synthesized from prostaglandin E1 (PGE1) and PGB2 was studied using two rat models. In an in vitro model, the brain was exposed to decapitation-ischemia, the cortex was removed and homogenized, and the formation of thiobarbituric acid reactive substances (TBAR) was measured after exposing the homogenate to in vitro reoxygenation either in the presence or absence of oligomers. It was found that these oligomers could inhibit lipid peroxidation, and that their activities were higher than that of superoxide dismutase (SOD). In an in vivo administration model, either the oligomer or the vehicle was injected i.p. 30 min before decapitation. The brain was exposed to decapitation-ischemia, the cortex was homogenized and exposed to 'in vitro' reoxygenation, after which TBAR value was determined. Ester-type compounds had a greater activity than free-acid type compounds in inhibiting lipid peroxidation. A possible mechanism of the protective effect of these oligomers in ischemia/reperfusion injury may be to scavenge oxygen free radicals.

DOI： 10.1016/0952-3278(92)90116-Z

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

By using the spin-trapping technique and electron spin resonance spectroscopy (ESR), we detected directly oxygen-derived free radicals in the brain exposed to ischemia and reperfusion. Forebrain ischemia was produced in the rat by bilateral occlusion of the common carotid arteries combined with hemorrhagic hypotension. The whole cerebral cortex was homogenized in the presence of the spin trap agent, N-tert-butyl-α-phenylnitrone, followed by a Folch extract. Spin-adducts were detected using ESR. As the index of tissue injury, the lipid peroxidation was estimated from both the amount of thiobarbituric acid reactive substance and the formation of conjugated diene. After 10 or 20 min of ischemia, reperfusion induced a burst of spin adduct formation which peaked at 5 min reperfusion time. The peak value increased with the ischemia time. The degree of lipid peroxidation, which was measured after 20 min of reperfusion, also increased with the ischemia time. When the oligomeric derivative was administered (9 mg · kg-1, i.p.) 30 min before ischemic insult, both spin adduct formation and lipid peroxidation were reduced. The results support the current view that free radicals produced upon reperfusion may be the direct cause of the subsequent lipid peroxidation.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCIENCE BV  

Forebrain ischemia was produced in the rat by bilateral occlusion of the common carotid arteries combined with hemorrhagic hypotension (30 mmHg). The whole cerebral cortex was homogenized in the presence of the spin trap agent N-tert-butyl-alpha-phenyl-nitrone, followed by a Folch extract. Spin-adducts were detected using electron spin resonance spectroscopy. The lipid peroxidation was estimated from both the amount of thiobarbituric acid reactive substance and the formation of conjugated diene. After 10 or 20 min of ischemia, reperfusion was initiated which induced an abrupt burst of free radical formation. The formation peaked at 5 min, and the peak value increased with the ischemia time. The degree of lipid peroxidation, which was measured after 20 min of reperfusion, also increased with the ischemia time. The results suggest that the lipid peroxidation may be the direct consequence of the action of free radicals formed during ischemia and reperfusion periods.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PERGAMON-ELSEVIER SCIENCE LTD  

A new oligomeric derivative was synthesized from prostaglandin B2 and ascorbic acid, and its effect on rat brain ischemia-reperfusion injury was studied. Brain ischemia was produced in the rat by the combination of bilateral common carotid artery occlusion and hemorrhagic hypotension (30 mmHg, 20 min). The cerebral cortex was homogenized in the presence of the spin trap agent, N-tert-butyl-alpha-phenyl-nitrone (PBN). Spin-adducts were detected using an electron spin resonance spectrometer (EPR). Lipid peroxidation was estimated from the amounts of both thiobarbituric acid reactive substances (TBAR) and conjugated diene. In control experiments, reperfusion induced a burst of free radical formation which peaked at 5 min reperfusion time (238 +/- 41 %). Lipid peroxidation increased significantly after 20 min of reperfusion (TBAR, 161 +/- 50 %; conjugated diene, 160 +/-29 %). When the oligomeric derivative was administered (9 mg/kg i.p. 30 min before ischemic insult), it significantly reduced both spin adduct formation (103 +/- 13 %) and lipid peroxidation (TBAR, 109 +/- 14 %; conjugated diene, 97 +/- 33 %).

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

We had a rare patient for adrenectomy who had aldosteronism complicated with hypertrophic cardiomyopathy (HCM). It has been suggested that aldosteronism could be the cause of HCM. The association is not clear in this case, but there is a possibility that myocardial hypertropy was deteriorated with hypertension caused by aldosteronism. Two important points of the anesthetic management of a patient with HCM are (1) to prevent direct or reflex increases in contractility, and (2) to maintain adequate preload and afterload. In a case complicated with aldosteronism, there is a risk that a significant increase in peripheral vascular resistance following the manipulation of the adrenal gland would aggravate left ventricular pressure load, resulting in a marked decrease in cardiac output. Therefore, in such a case, vasodilators which are said to be poorly tolerated in a patient with HCM might be considered to facilitate the anesthetic management, provided that the vascular system is kept appropriately full. In this case, we employed enflurane-oxygen-nitrous oxide with fentanyl to keep deep levels of general anesthesia. Nitroglycerin (NTG) was used when arterial pressure increased suddenly with the manipulation of the adrenal gland. The effect of NTG is not definitely convincing since blood pressure returned to normal after adrenal excision. But the fact that pulmonary capillary wedge pressure decreased with infusion of NTG suggests improvement of hemodynamic function.

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記述言語：日本語   掲載種別：研究論文（学術雑誌）