EXOCRINE HYPERSTIMULATION BUT NOT PANCREATIC DUCT OBSTRUCTION INCREASES THE SUSCEPTIBILITY TO ALCOHOL-RELATED PANCREATIC INJURY

Objective: To evaluate the factors thought to be involved in the patho genesis of acute pancreatitis associated with alcohol. Background: The mechanism of alcohol-induced pancreatitis is believed to involve syne rgistic effects of various pathogenetic factors. The present study was designed to evaluate the possible contribution of pancreatic duct obs truction, physiologic exocrine stimulation, or secretory hyperstimulat ion to alcohol-induced pancreatic injury. Methods: Wistar rats were al located randomly to a control group (group 1), or to a group with panc reatic duct obstruction (group 2), physiologic exocrine stimulation (g roup 3), ductal obstruction and exocrine stimulation (group 4), or exo crine hyperstimulation with the cholecystokinin analogue cerulein (gro up 5). Three hours after this pretreatment, animals in each experiment al group were randomly divided into two subgroups for intragastric adm inistration of either water (groups 1A through 5A) or beer (groups 1B through 5B). Test solutions were instilled over 9 hours (total amount of alcohol administered, 4.8 g/kg). Twenty-four hours after beginning the test infusion, animals were killed for histologic evaluation of pa ncreatic edema and determination of an acinar cell necrosis score. Ser um amylase levels were determined at 3, 9, and 24 hours. Results: No i ncrease in amylase levels or significant morphologic changes were foun d in control animals (group 1A) or in animals subjected to physiologic exocrine stimulation (group 2A). Pancreatic duct obstruction, with or without physiologic exocrine hyperstimulation (groups 3A and 4A), and exocrine hyperstimulation (group 5A) induced pancreatitis of similar severity with minor acinar cell damage. Alcohol superimposed on exocri ne hyperstimulation (group 5B) increased acinar cell injury (group 5A, 0.4+/-0.1 points vs 5B, 1.0+/-0.2 points; P<.05) and serum amylase le vels at 24 hours (group 5a, 41+/-6 U/L vs group 5B, 72+/-11 U/L; P<.O5 ), whereas no differences between subgroups A and B (water vs beer) we re found in groups 1 through 4. Conclusion: Our findings suggest that the pathogenesis of acute alcoholic pancreatitis may require a state o f exocrine hyperstimulation, perhaps via cholecystokinin, but do not s upport a role for constriction or obstruction of Oddi's sphincter.