The bradykinin antagonist CP-0597 can limit the progression of postischemic pancreatitis.
Bradykinin mediates the inflammatory process of acute pancreatitis characterized by an increase of microvascular permeability, vasodilation and leukocyte activation. These phenomena are characteristic also for the ischemia/reperfusion injury of the pancreas, which in time is considered a causative factor in the pathogenesis of acute pancreatitis. The aim of this study was to investigate the influence of the bradykinin B2 receptor antagonist CP-0597. After complete ischemia/reperfusion of the pancreas in rats there is progression from postischemic acute edema to necrotizing pancreatitis over a reperfusion period of 5 days. In 8 Sprague-Dawley rats (treatment group) 18 micrograms/kg/h CP-0597 was administered intraperitoneally over 5 days with an osmotic minipump starting 15 min before release of 2 h ischemia. Animals of the placebo group (n = 8) were identically treated, but received the solvent, phosphate buffer. Animals of a control group (n = 7) underwent sham operation without ischemia. After 5 days the animals were sacrificed for histology. No morphological changes of the pancreatic gland were observed in the control group. Ischemia for 2 h resulted in necrotizing pancreatitis with high mortality (4/8 animals) during the reperfusion period of 5 days. In contrast, all animals in the treatment group survived without clinical or histological signs of necrotizing pancreatitis.
Hoffmann
T F
TF
Institute for Surgical Research, University of Munich, Germany.
Waldner
H
H
Messmer
K
K
D000208:Acute Disease; D000681:Amylases / Q000378:metabolism; D000818:Animals; D001920:Bradykinin / Q000037:antagonists & inhibitors*; D065168:Bradykinin Receptor Antagonists; D007511:Ischemia / Q000150:complications; D007958:Leukocyte Count; D009842:Oligopeptides / Q000494:pharmacology*; D010179:Pancreas / Q000098:blood supply / Q000201:enzymology / Q000473:pathology; D010195:Pancreatitis / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D043782:Receptor, Bradykinin B2; D015427:Reperfusion Injury / Q000188:drug therapy / Q000209:etiology / Q000473:pathology
D065168:Bradykinin Receptor Antagonists; D009842:Oligopeptides; D043782:Receptor, Bradykinin B2; D000681:Amylases; D001920:Bradykinin