Satake K, Ha S S, Hiura A, Nishiwaki H
First Department of Surgery, Osaka City University Medical School, Japan.
Gastroenterol Jpn. 1993 Feb;28(1):64-71. doi: 10.1007/BF02775005.
The therapeutic effect of a new synthetic protease inhibitor on hemodynamic changes was studied in experimental acute pancreatitis. Pancreatitis was induced by the injection of autologous bile mixed with trypsin into the main pancreatic duct after ligating the accessory duct. Plasma beta-endorphin concentrations and cardiovascular function were measured. Seventeen dogs (control group) were given 10 ml/kg/hr of lactate Ringer's solution intravenously 1 hr before the induction of pancreatitis and throughout the experiment. Seven dogs (the low protease inhibitor group) were given an intravenous bolus injection of 0.4 mg/kg of a new synthetic protease inhibitor, E-3123 (4-(2-succiminido-ethylthio)4-geranidinobenzoate methanesulfate) 30 min after the induction of pancreatitis and then a continuous intravenous infusion at 3 micrograms/kg/min throughout the experiment. Seven dogs (the high protease inhibitor group) received an intravenous bolus injection of 3 mg/kg and a continuous intravenous infusion at 50 micrograms/kg/min of E-3123 according to the same method as in the low protease inhibitor group. The mortality rate during the experiment was 41% (7/17) in the control group, 28.5% (2/7) in the high protease inhibitor group and 0% in the low protease inhibitor group. The increase in the plasma beta-endorphin levels in the control group was statistically significant. When E-3123 was given 30 min after the induction of pancreatitis, the increase in the plasma beta-endorphin levels in the high protease inhibitor group was also found to be increased statistically significant, compared with preinduction levels, but the increase was statistically significantly lower than that in the control group. Plasma beta-endorphin levels in the low protease inhibitor group, however, did not increase.(ABSTRACT TRUNCATED AT 250 WORDS)
在实验性急性胰腺炎中研究了一种新型合成蛋白酶抑制剂对血流动力学变化的治疗效果。通过在结扎副胰管后将自体胆汁与胰蛋白酶混合注入主胰管来诱导胰腺炎。测量血浆β-内啡肽浓度和心血管功能。17只狗（对照组）在诱导胰腺炎前1小时及整个实验过程中静脉内给予10 ml/kg/hr的乳酸林格氏液。7只狗（低蛋白酶抑制剂组）在诱导胰腺炎后30分钟静脉推注0.4 mg/kg的新型合成蛋白酶抑制剂E-3123（4-(2-琥珀酰亚胺基-乙硫基)4-香叶基苯甲酸甲磺酸盐），然后在整个实验过程中以3微克/千克/分钟的速度持续静脉输注。7只狗（高蛋白酶抑制剂组）按照与低蛋白酶抑制剂组相同的方法接受3 mg/kg的静脉推注和50微克/千克/分钟的E-3123持续静脉输注。实验期间对照组的死亡率为41%（7/17），高蛋白酶抑制剂组为28.5%（2/7），低蛋白酶抑制剂组为0%。对照组血浆β-内啡肽水平的升高具有统计学意义。在诱导胰腺炎后30分钟给予E-3123时，高蛋白酶抑制剂组血浆β-内啡肽水平与诱导前水平相比也有统计学意义的升高，但升高幅度在统计学上显著低于对照组。然而，低蛋白酶抑制剂组的血浆β-内啡肽水平并未升高。（摘要截短至250字）
