Early development of experimental biliary pancreatitis and its amelioration by CCK-receptor blockade.

OBJECTIVE

Development of pancreatitis has extensively been studied in models using CDE-diet and cerulein. This study analyzes early alterations and effects of CCK-receptor blockade in a model of biliary pancreatitis which better reflects the pathogenesis of human pancreatitis.

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 every 6 hours. Morphological alterations were quantified by histological grading. Biochemical evidence of pancreatitis was assessed by determination of amylase concentrations in serum and ascites. A bioassay was used to determine plasma cholecystokinin.

RESULTS

Ligation of the common bile and pancreatic duct caused an increase in serum amylase, development of ascites with high amylase concentrations, and morphological evidence of pancreatitis without major mortality. Electron microscopy showed early loss of microvilli and defects in basal lamina representing initial stages of duct ruptures. Early ultrastructural damage to acini included multiple vacuoles, peripheral loss of density of ("targetoid") zymogen granules and dilatation of RER. Acinar vacuolization, edema, hemorrhage and necrosis mainly occurred in areas neighboring the ducts. Duct ligation was associated with a significant increase in plasma CCK. The CCK-antagonist significantly reduced the biochemical and morphological severity of obstructive pancreatitis.

CONCLUSIONS

Obstruction of the common channel of the bile and pancreatic ducts results in transient mild to moderate acute pancreatitis and in an increase in plasma CCK. Since CCK-receptor blockade ameliorated the severity of pancreatitis it is likely that increased plasma CCK plays a contributory or permissive role in pancreatitis caused by duct obstruction.