THE BRADYKININ ANTAGONIST CP-0597 CAN LIMIT THE PROGRESSION OF POSTISCHEMIC PANCREATITIS

Bradykinin mediates the inflammatory process of acute pancreatitis cha racterized 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 cons idered a causative factor in the pathogenesis of acute pancreatitis. T he aim of this study was to investigate the influence of the bradykini n B-2 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 mu g/kg/h CP-0597 was a dministered intraperitoneally over 5 days with an osmotic minipump sta rting 15 min before release of 2 h ischemia. Animals of the placebo gr oup (n = 8) were identically treated, but received the solvent, phosph ate buffer. Animals of a control group (n = 7) underwent sham operatio n without ischemia. After 5 days the animals were sacrificed for histo logy. No morphological changes of the pancreatic gland were observed i n the control group. Ischemia for 2 h resulted in necrotizing pancreat itis with high mortality (4/8 animals) during the reperfusion period o f 5 days. In contrast, all animals in the treatment group survived wit hout clinical or histological signs of necrotizing pancreatitis.