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  • Title: The bradykinin antagonist CP-0597 can limit the progression of postischemic pancreatitis.
    Author: Hoffmann TF, Waldner H, Messmer K.
    Journal: Immunopharmacology; 1996 Jun; 33(1-3):243-6. PubMed ID: 8856157.
    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.
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