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