CHARACTERIZATION OF A NONINVASIVE, VASCULAR MODEL OF ACUTE NECROTIZING PANCREATITIS

One of the vasoactive peptides that has been implicated in the progres sion from edematous to necrotizing pancreatitis is bradykinin. We have investigated the effect of bradykinin administration and bradykinin i nhibition on an edematous model of acute pancreatitis in rats (10 mu g /kg/h of caerulein i.v.). Within six hours i.v. bradykinin reduced cir culating serum amylase levels significantly but neither affected tissu e edema nor morphology. A bradykinin antagonist (HOE-140), on the othe r hand, reduced pancreatic edema by 70% and converted edematous pancre atitis into a hemorrhagic and necrotizing variety of the disease. In f urther experiments we determined the time course and the minimal dosag e required for the induction of this severe and non-invasive disease v ariety. A single dose of caerulein (40 mu g/kg i.p.) together with a s ingle administration of the bradykinin antagonist HOE-140 (100 mu g/kg s.c.) consistently resulted in hemorrhagic necrosis of the pancreas w ithin six hours. We conclude that this simple protocol allows for the non-invasive induction of a vascular model of necrotizing pancreatitis and appears ideally suited to study the development of this severe fo rm of the disease.