Pathophysiology of multiple organ failure during severe acute pancreatitis and it s treatment.

重症急性胰腺炎多器官功能衰竭的病理生理学及其治疗。

• 批准号: 03670638
• 负责人: SATAKE Katsusuke
• 金额: $ 0.9万
• 依托单位: Osaka City University Medical School
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1991
• 资助国家: 日本
• 起止时间: 1991 至 1992
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-03670638/
• 关键词: Severe acute pancreatitis; Hemodynamic changes; Protease inhibitor; beta-endorphin; CCK-receptor antagonist; Cholecystokinin (CCK); Closed duodenal loop; CCK; CCK-receptor拮抗剤; Severe acute pancreatitis; Hemodynamic changes; Protease inhibitor; beta-endorphin; CCK-receptor antagonist; Cholecystokinin (CCK); Closed duodenal loop; CCK; CCK-receptor拮抗剤

1) Acute pancreatitis is a disease of variable intensity, ranging a mild, self-limiting disease to a life-threating condition causing multiple organ failure. The important causes of morbidity and mortality in patients with acute pancreatitis include shock and cardiovascular dysfunction, respiratory and renalfailure etc. These effects may be caused by hypovolemia from fluid requestration around the pancreas, which may release a myocardial depressant factor vasoactive substances. Our recent work has shown that beta-emdorphin may play an important role in the complicated physiopathologic balance of hypotension and myocardial depression in acute pancreatitis. Although the mechanism of beta-endorphin release during acute pancreatitis is unknown, it has been reported that trypsin like enzyme and bradykinin, released by noxious stimuli, induces the production and the liberation of beta-endorphin. In addition, trypsin-like activity and serum bradykinin levels increase during acute pancreatitis … More .Recently, various protease inhibitors have been developed and widely used for the treatment of acute pancreatitis, but been developed and widely used for the treatment of acute pancreatitis, but their efficacy is controversial. Protease inhibitors can inhibit serine protease such as trypsin, kallikrein etc. which suggests that beta-endorphin release during acute pancreatitis may be prevented by protease inhibitors through the inhibition of trypsin-like enzymes and bradykinin release. However, there are no reports of the effect of protease inhibitors on beta-endorphin release or on hemodynamic changes during acute pancreatitis.Pancreatitis was induced by the injection of autologous bile mixed with trypsin into the main pancreatic duct after ligation of the accessory duct. Plasma beta-endorphin levels and cardiovascular function were measured. Control group was given 10 ml/kg/h of lactate Ringer s solution intravenously beginning 1 h before the induction of pancreatitis. Protease inhibitor received an intravenous infusion of 3 mg/kg/h of a synthetic protease inhibitor in lactate Ringers's solution soon after the induction of pancreatitis.Plasma beta-endorphin levels in the control group increased significantly. However, plasma beta-endorphin levels in the protease inhibitor group did not increase as in the control group. The protease infusion improved hypotension, myocardial depression and plasma lactate, suggesting that the inhibitory effect of the protease inhibitor on beta-endorphin release contribute to the improvement. Furthermore, protease inhibitor infusion 30min after the indication of pancreatitis showed the same effect.2) Submaximal administration of cholecystokinin (CCK) or analogs (cerulein) induces edematous acute pancreatitis. In addition, introvenous injection of these hormones has been shown to warsen the morbidity and mortality in experimental acute pancreatitis.Creation of a closed duodenal loop produced edematous acute pancreatitis at 6 h later and hemorrhagic acute pancreatitis at 12 h later and the pancreatitis established tended to improve after releasing the loop.We investigated the effect of a CCK-receptor antagonist on the healing process in edematous and hemorrhagic acute pancreatitis after releasing the loop. In the group treated with a CCK-receptor antagonist, serum amylase and lipase levels decreased markedsly upon release the loop in edematous acute pancreatitis compared with the control group.Further more, the histological changes in edematous acute pancreatitis improved more rapidly than in the control group. No such biochemical and histological evidence of improvement was observed in hemorrhagic acute pancreatitis. The CCK-receptor antagonist displayed a therapeutic effect in edematous acute pancreatitis. These findings suggests that endogenous CCK release induced by the closed cluodenal loop may have a contributory role in the development of edematous acute pancreatitis but not of hemorrhagic acute pancreatitis. Less

1）急性胰腺炎是一种可变强度的疾病，将一种轻度的自限性疾病范围为危及生命的疾病，导致多器官衰竭。急性胰腺炎患者发病率和死亡率的重要原因包括休克和心血管功能障碍，呼吸和肾拖网。这些作用可能是由于胰腺周围液体请求不足引起的，可能会释放心肌抑制因子血管活性物质。我们最近的工作表明，β-巨啡可能在急性胰腺炎中低血压和心肌抑郁症的复杂生理病理学平衡中起重要作用。尽管在急性胰腺炎期间β-内啡肽释放的机制尚不清楚，但据报道，有害刺激释放的胰蛋白酶和促蛋白酶像酶和心动激肽一样，诱导β-内啡肽的产生和解放。此外，急性胰腺炎期间胰蛋白酶样活性和串行松曲素水平升高……更重要的是，已经开发并广泛用于治疗急性胰腺炎，但被开发并广泛用于治疗急性胰腺炎，但其有效性是有争议的。蛋白酶抑制剂可以抑制丝氨酸蛋白，例如胰蛋白酶，kallikrein等，这表明蛋白质抑制剂在急性胰腺炎期间的β-内啡肽在急性胰腺炎期间的释放可以通过抑制胰蛋白酶样酶和bradylykilin释放来预防。但是，尚无关于蛋白质抑制剂对β-内啡肽释放的作用或急性胰腺炎期间血液动力学变化的报道。通过将自体胆汁与胰蛋白酶混合在辅助导管结扎后诱导的自体胆汁炎。测量了血浆β-内啡肽水平和心血管功能。从诱导胰腺炎开始前1小时，对对照组的乳酸铃声溶液给予了10 mL/kg/h的溶液。蛋白酶抑制剂在诱导胰腺炎后不久，在乳酸铃声溶液中接受了3 mg/kg/h的静脉输注。对照组的血β-内啡肽水平显着增加。然而，蛋白质抑制剂组中的血浆β-内啡肽水平没有像对照组那样增加。蛋白酶输注改善了低血压，心肌抑郁症和血浆乳酸，表明蛋白酶抑制剂对β-内啡肽释放的抑制作用有助于改善。此外，胰腺炎指示后30分钟的蛋白酶抑制剂输注表现出相同的作用。2）次临时施用胆囊化蛋白（CCK）或类似物（Cerulein）（Cerulein）会诱导肿瘤性急性胰腺炎。 In addition, introvenous injection of these horrmones has been shown to warsen the morbidity and mortality in experimental acute pancreatitis.Creation of a closed duodenal loop produced edematous acute pancreatitis at 6 h later and hemorrhagic acute pancreatitis at 12 h later and the pancreatitis established tended to improve after releasing the loop.We investigated the effect of a CCK受体拮抗剂在释放环后在水肿和出血性急性胰腺炎中的愈合过程中进行拮抗剂。与对照组相比，在用CCK受体拮抗剂治疗的组中，血清淀粉酶和脂肪酶水平显着发展，比对照组相比，多余的急性胰腺炎的组织学变化更快地改善了。在出血性急性胰腺炎中未观察到这种改善的生化和组织学证据。 CCK受体拮抗剂在水肿急性胰腺炎中表现出治疗作用。这些发现表明，封闭的氯二烯环路诱导的内源性CCK可能在水肿急性急性胰腺炎的发展中起作用，而不是出血性急性急性胰腺炎。较少的