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The therapeutic effect of a new synthetic protease inhibitor (E-3123) on hemodynamic changes during experimental acute pancreatitis in dogs


, : The therapeutic effect of a new synthetic protease inhibitor (E-3123) on hemodynamic changes during experimental acute pancreatitis in dogs. Gastroenterologia Japonica 28(1): 64-71

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 mu-g/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 mu-g/kg/min of E-3123 according to the same method as in the 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. The protease inhibitor infusion as used in this experiment can bring about improvement in hypotension and myocardial depression to an extent by inhibiting the release of beta-endorphin, suggesting that the inhibitory effect of the protease inhibitor on beta-endorphin release contributes to the improvement in hemodynamic changes during pancreatitis. There may also be an optimal therapeutic dose of this drug for the treatment of hypotension and myocardial depression secondary to beta-endorphin release.

US$19.90

PMID: 8440425

DOI: 10.1007/bf02775005


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