Effect of a new cholecystokinin receptor antagonist (KSG 504) on the early stage of the healing process in acute pancreatitis induced in rats by the closed duodenal loop technique.

Abstract

Creation of a closed duodenal loop produced edematous acute pancreatitis within 6 h and hemorrhagic acute pancreatitis within 12 h in male Sprague-Dawley rats. The pancreatitis thus established tended to improve after releasing the loop. We investigated the effect of a new cholecystokinin receptor antagonist, KSG 504, on the healing process in edematous and hemorrhagic acute pancreatitis after releasing the loop. Serum amylase and lipase levels in the control group decreased gradually after releasing the loop, but the reductions were not significant. In both the group treated with KSG 504 intravenously and the group treated subcutaneously, serum amylase and lipase levels decreased markedly upon release of the loop in edematous acute pancreatitis. Furthermore, the histologic changes in edematous acute pancreatitis improved more rapidly than in the control group. However, no such biochemical or histologic evidence of improvement was observed in hemorrhagic acute pancreatitis. The new cholecystokinin receptor antagonist, KSG 504, displayed a therapeutic effect in edematous acute pancreatitis but not in hemorrhagic acute pancreatitis. These findings suggest that endogenous cholecystokinin release induced by the closed duodenal loop may have a contributory role in the development of edematous acute pancreatitis but not of hemorrhagic acute pancreatitis.