Exocrine hyperstimulation but not pancreatic duct obstruction increases the susceptibility to alcohol-related pancreatic injury
T. Foitzik, K. B. Lewandrowski, C. Fernandez-del Castillo, D. W. Rattner, E. Klar and A. L. Warshaw
Department of Surgery, Massachusetts General Hospital, Boston.
OBJECTIVE: To evaluate the factors thought to be involved in the
pathogenesis of acute pancreatitis associated with alcohol. BACKGROUND: The
mechanism of alcohol-induced pancreatitis is believed to involve
synergistic effects of various pathogenetic factors. The present study was
designed to evaluate the possible contribution of pancreatic duct
obstruction, physiologic exocrine stimulation, or secretory
hyperstimulation to alcohol-induced pancreatic injury. METHODS: Wistar rats
were allocated randomly to a control group (group 1), or to a group with
pancreatic duct obstruction (group 2), physiologic exocrine stimulation
(group 3), ductal obstruction and exocrine stimulation (group 4), or
exocrine hyperstimulation with the cholecystokinin analogue cerulein (group
5). Three hours after this pretreatment, animals in each experimental group
were randomly divided into two subgroups for intragastric administration 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 pancreatic edema
and determination of an acinar cell necrosis score. Serum amylase levels
were determined at 3, 9, and 24 hours. RESULTS: No increase in amylase
levels or significant morphologic changes were found 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 exocrine 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 levels at 24 hours (group 5a, 41
+/- 6 U/L vs group 5B, 72 +/- 11 U/L; P < .05), whereas no differences
between subgroups A and B (water vs beer) were found in groups 1 through 4.
CONCLUSION: Our findings suggest that the pathogenesis of acute alcoholic
pancreatitis may require a state of exocrine hyperstimulation, perhaps via
cholecystokinin, but do not support a role for constriction or obstruction
of Oddi's sphincter.
