EARLY DEVELOPMENT OF EXPERIMENTAL BILIARY PANCREATITIS AND ITS AMELIORATION BY CCK-RECEPTOR BLOCKADE

Background/Aims: Development of pancreatitis has extensively been stud ied in models using CDE-diet and cerulein. This study analyzes early a lterations and effects of CCK-receptor blockade in a model of biliary pancreatitis which better reflects the pathogenesis of human pancreati tis. Material and Methods: The common part of the bile and pancreatic duct was surgically ligated in fed rats which were allowed to recover. The CCK-antagonist CR1409 at 10 mg/kg or 0.9% NaCl was s.c. given eve ry 6 hours. Morphological alterations were quantified by histological grading Biochemical evidence of pancreatitis was assessed by determina tion of amylase concentrations in serum and ascites. A bioassay was us ed to determine plasma cholecystokinin. Results: Ligation of the commo n bile and pancreatic duct caused an increase in serum amylase, develo pment of ascites with high amylase concentrations, and morphological e vidence of pancreatitis without major mortality. Electron microscopy s howed early loss of microvilli and defects in basal; lamina representi ng initial stages of duct ruptures. Early ultrastructural damage to ac ini included multiple vacuoles, peripheral loss of density of (''targe toid'') zymogen granules and dilatation of RER. Acinar vacuolization, edema, hemorrhage and necrosis mainly occurred in areas neighboring th e ducts. Duct ligation was associated with a significant increase in p lasma CCK. The CCK-antagonist significantly reduced he biochemical and morphological severity of-obstructive pancreatitis. Conclusions: Obst ruction of the common channel of the bile and pancreatic ducts results in transient mild to moderate acute pancreatitis and in an increase i n plasma CCK. Since CCK-receptor blockade ameliorated the severity of pancreatitis it is likely that increased plasma CCK plays a contributo ry or permissive role in pancreatitis caused by duct obstruction.