Effects of oral agents on pancreatic duct permeability: a model of acute alcoholic pancreatitis

The main pancreatic duct can be made permeable to molecules of up to 20,000 daltons by oral pretreatment with aspirin and ethanol. Because pancreatic enzymes have similar molecular weights, we hypothesized that activated pancreatic enzymes would leak from a permeable duct and produce pancreatitis. Four groups of cats were pretreated with either milk, aspirin, ethanol, or aspirin and ethanol for 48 hr. Then pancreatic juice (either activated by enterokinase or nonactivated) was perfused along the duct from tail to duodenum. Twenty-four hours later the animals were examined. Animals pretreated with aspirin, ethanol, or both, and in which ducts were perfused with activated juice, developed acute edematous pancreatitis. Animals that had perfusion with nonactivated enzymes had pancreases indistinguishable from control animals. Morphological studies on ductal permeability in animals pretreated with ethanol and aspirin showed electron-dense material (believed to be dextran) between the basal plasma membrane and basal lamina, and in the basal intercellular space.