Characterization of a non-invasive, vascular model of acute necrotizing pancreatitis

One of the vasoactive peptides that has been implicated in the progression from edematous to necrotizing pancreatitis is bradykinin. We have investigated the effect of bradykinin administration and bradykinin inhibition on an edematous model of acute pancreatitis in rats (10 micrograms/kg/h of caerulein i.v.). Within six hours i.v. bradykinin reduced circulating serum amylase levels significantly but neither affected tissue edema nor morphology. A bradykinin antagonist (HOE-140), on the other hand, reduced pancreatic edema by 70% and converted edematous pancreatitis into a hemorrhagic and necrotizing variety of the disease. In further experiments we determined the time course and the minimal dosage required for the induction of this severe and non-invasive disease variety. A single dose of caerulein (40 micrograms/kg i.p.) together with a single administration of the bradykinin antagonist HOE-140 (100 micrograms/kg s.c.) consistently resulted in hemorrhagic necrosis of the pancreas within 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 form of the disease.