Acute pancreatitis is a common illness that accounts for considerable morbidity and mortality. Little is known concerning the pathogenesis of this disease and therefore the treatment is primarily supportive and symptomatic care. A variety of stimuli are capable of initiating an episode of acute pancreatitis. These include alcohol ingestion, gallstones and ischemia. Utilizing the ex vivo, isolated perfused canine pancreas preparation, experimental acute pancreatitis can be initiated by a variety of stimuli. Alcholic hyperlipemic pancreatitis can be simulated in this preparation by infusing oleic acid into the arterial line. Gallstone pancreatitis can be simulated by partially obstructing the pancreatic duct and maximally stimulating the gland with secretin. Ischemic pancreatitis can be induced in this preparation by a period of total ischemia before the perfusion is started. The pancreatitis in all three models is manifest by weight gain and hyperamylasemia. In all instances, the first physiologic change identifiable is edema formation secondary to an increase in capillary permeability. Recent work has suggested that the capillary injury is mediated, at least in part, by the production of oxygen derived free radicals. In all three models of acute pancreatitis, the initial physiologic response (an increase in capillary permability) and its biochemical mediators (oxygen derived free radicals) appear to be the same, despite the fact that the stimuli initiating the acute pancreatitis are markedly disparate. This suggests a final common pathway by which acute pancreatitis is initiated. By studying the biochemical and physiologic changes that occur following the initiating stimulus, information concerning the pathogenic pathways of experimental pancreatitis can be gained, and effective treatment developed. In addition, a clinical trail will be carried out evaluating the effectiveness of an inhibitor of free radical production (allopurinol) in preventing the development of acute pancreatitis and/or hyperamylasemia following endoscopic retrograde pancreatography.
