title: The bradykinin antagonist CP-0597 can limit the progression of postischemic pancreatitis.
abstract: 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.
authors.affiliation: Institute for Surgical Research, University of Munich, Germany.
authors.forename: T F
authors.initials: TF
authors.lastname: Hoffmann
authors.forename: H
authors.initials: H
authors.lastname: Waldner
authors.forename: K
authors.initials: K
authors.lastname: Messmer
mesh_terms: 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
chemical_list: D065168:Bradykinin Receptor Antagonists; D009842:Oligopeptides; D043782:Receptor, Bradykinin B2; D000681:Amylases; D001920:Bradykinin