Tf. Hoffmann et al., THE BRADYKININ ANTAGONIST CP-0597 CAN LIMIT THE PROGRESSION OF POSTISCHEMIC PANCREATITIS, Immunopharmacology, 33(1-3), 1996, pp. 243-246
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.