Effects of anesthetic drugs on ischemia-reperfusion induced organ damage

麻醉药物对缺血再灌注器官损伤的影响

• 批准号: 06454449
• 负责人: TAKEDA Junzo
• 金额: $ 3.84万
• 依托单位: Keio University, School of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1994
• 资助国家: 日本
• 起止时间: 1994 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-06454449/
• 关键词: ischemia-reperfusion injury; cardiopulmonary bypass; esophagectomy; aortic surgery; neutrophil; anesthetics; xanthine oxidase; 好中球化学発光; 好中球エラスターゼ; 虚血再灌流障害; 虚血性肝障害; 吸入麻酔薬; 静脈麻酔薬; 虚血細灌流傷害、; 吸入麻酔薬、; 好中球化学発光、; キサンチンオキシダーゼ、

In this research project, the investigators underwent both laboratory and clinical investigation. We investigated the effects of various anesthetic agents on the function of vascular endothelial cells and neutrophils which plays a central role in ischemia-reperfusion organ injury.1.Laboratory Investigation First, we established ischemia-reperfusion model of bilateral hind limb and abdominal organs in rabbits. Then we investigated endothelial and neutrophil activation and organ damage induced by ischemia-reperfusion. We also studied whether anesthetic management influence these changes. The results indicates that anesthetic agent significantly influenced the neutrophil activaition and organ injury during ischemia-reperfusion. More specifically, sevoflurane and propofol attenuated eggegerated neutrophil activation induced by ischemia-reperfusion. These anesthetic agents also prevented ischemia-reperfusion induced organ damage. We also found neuraxial blockage suppressed neutrophil activation in the same model. We intend to investigate pharmacological intervention to the neutrophil activaition.2.Clinical Investigation We investigated the functional change of vascular endothelial cells and neutrophils during cardiopulmonary bypass and perioperative period of esophageal resection. During cardiopulmonary bypass, neutrophils were significantly activated after the cross clamp release. The results also indicates the degree of neutrophil activation correlated postoperative pulmonary dysfucntion. In esophagectomy cases, neutrophil activation occured 24 hours after sugery started. We aim further investigation on ischemia-reperfusion injury of liver and intestine.

在本研究项目中，研究者进行了实验室和临床研究。本研究探讨了不同麻醉剂对缺血再灌注损伤中起核心作用的血管内皮细胞和中性粒细胞功能的影响。1.实验室研究首先建立了家兔双侧后肢和腹部器官缺血再灌注模型。然后，我们研究了内皮细胞和中性粒细胞活化和器官损伤引起的缺血再灌注。我们还研究了麻醉管理是否影响这些变化。结果表明，麻醉剂对缺血再灌注时中性粒细胞的活化和器官损伤有明显影响。更具体地说，七氟烷和丙泊酚减弱了缺血再灌注诱导的中性粒细胞活化。这些麻醉剂也防止缺血-再灌注诱导的器官损伤。我们还发现，在同一模型中，轴突阻滞抑制中性粒细胞活化。本研究旨在探讨药物对中性粒细胞活化的干预作用。2.临床研究我们观察了体外循环和食管癌切除术围手术期血管内皮细胞和中性粒细胞的功能变化。在体外循环期间，中性粒细胞在交叉夹释放后显著活化。中性粒细胞活化程度与术后肺功能障碍有关。在食管切除术病例中，中性粒细胞活化发生在手术开始后24小时。本实验旨在进一步研究肝、肠缺血再灌注损伤。

项目成果

Matsumoto, Kotake et al.: "EAC does not represent neutrophil function to release elastase in the patients undergoing esophagectomy" Anesth Analg. 82. 2S S305 (1996)

Matsumoto、Kotake 等人：“EAC 并不代表接受食管切除术的患者中中性粒细胞释放弹性蛋白酶的功能”Anesth Analg。

Hiyama A,Takeda J,et al.: "A human urinary protease inhibitor(Ulinastatin)inhibits neutrophil extracellular release of elastase during cardiopulmonary bypass" J.Cardiothoracic Vasc Anesth. (発表予定).

Hiyama A、Takeda J 等人：“人尿蛋白酶抑制剂（乌司他丁）在心肺转流过程中抑制中性粒细胞胞外弹性蛋白酶的释放”J.Cardiothoracic Vasc Anesth（待提交）。

松本みどり: "食道癌周術期における好中球エラスターゼ放出能による好中球機能の評価" 麻酔. 46 1. 23-30 (1997)

Midori Matsumoto：“食管癌围手术期中性粒细胞弹性蛋白酶释放能力评估中性粒细胞功能”麻醉46 1. 23-30 (1997)。

Matsumoto M,Kotake Y,et al.: "EAC does not represent neutrophil function to release elastase in the patients undergoing esophagectomy" Anesth Analg. 82,2S. S305 (1996)

Matsumoto M、Kotake Y 等人：“EAC 并不代表接受食管切除术的患者中中性粒细胞释放弹性蛋白酶的功能”Anesth Analg。

Matsumoto: "Evaluation of neutrophil activation using elastase releasing capacity in vitro during perioperative period of esophagectomy" Masui (Jpn.J.Anesthesiol.). 46. 23-30 (1997)

Matsumoto：“食管切除术围术期体外使用弹性蛋白酶释放能力评估中性粒细胞活化”Masui（Jpn.J.Anesthesiol.）。