Mayumi Yamano, Keiji Miyata and Toshimitsu Yamada
Pharmacology Laboratories, Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd., 21 Miyukigaoka, Tsukuba, Ibaraki 305-8585, Japan
Abstract: Effects of retrograde injection into the pancreatic duct and intravenous infusion of pancreatic enzymes and bile salt on the pancreas and other vital organs such as the liver and the lung were investigated in rats. Intraductal injection (1 ml/kg) of alpha-chymotrypsin (50 - 100 mg/ml), trypsin (10 - 100 mg/ml), pancreatic elastase (10 mg/ml), lipase (100 - 300 mg/ml), pancreatic kallikrein (25 mg/ml) and sodium taurocholate (50 mg/ml) solutions significantly increased pancreatic water content. alpha-Chymotrypsin, pancreatic elastase, taurocholate and trypsin elicited gross pancreatic hemorrhage. In contrast, lipase and kallikrein elicited gross pancreatic edema, but not hemorrhage. Intravenous infusion of trypsin (1 mg/kg/hr) and pancreatic elastase (10 mg/kg/hr) significantly increased pulmonary vascular permeability in rats, whereas infusion of neutrophil elastase (0.3 mg/kg/hr) did not elicit these effects. Only trypsin slightly reduced arterial oxygen pressure. These results show pancreatic enzymes and bile salts induce pancreatic inflammation after retrograde injection into the pancreatic duct in rats. Furthermore, trypsin and pancreatic elastase extravasation into the vascular system can lead to pulmonary dysfunction in rats.
Keywords: Acute pancreatitis, Pancreatic enzyme, Pulmonary dysfunction, Trypsin, Elastase