Factors influencing the inflammatory response and secondary infection in rat pancreatitis

• A rat~model for bile-induced acute pancreatitis is used throughout the experiments. The model, which is well known, mimics the assumed events leading to biliary pancreatitis. The mortality from acute pancreatitis with this model was 23-33% and 73% of all deaths occurred within the first 24 hours.Cholecystokinin (CCK) is the strongest known stimulant of pancreatic enzyme secretion and pancreatic growth. During acute pancreatitis, stimulation with the CCK agonist cerulein augmented the pancreatitis. Blocking of the endogenous CCK by the CCK-receptor antagonist proglumide had no beneficial effect.Resorption of biologically active substances via the peritoneum has been suggested as a pathogenetic mechanism for systemic complications in acute pancreatitis. Peritoneal resorption of fluorescein-isothiocyanate-conjugated dextran 10 000 was studied in rats during acute pancreatitis induced by different means or with bacterial peritonitis. Peritoneal permeability was independent of both induction mode and severity of acute pancreatitis and of whether peritoneal inflammation was induced directly by bacteria or indirectly by pancreatitis. Absorption of toxic substances via the peritoneum seems to be of minor importance for the development of systemic complications in acute pancreatitis.Bacterial peritonitis resulted in hyperamylasemia. Light and electron microscopy in these cases revealed no damage to the exocrine pancreas. The amylase therefore was not of pancreatic origin.Reflux of infected bile or duodenal contents into the pancreatic duct can give rise to infected acute pancreatitis. Rats given infected bile into the pancreatic duct showed incresed consumption of C3, anergy to a recall antigen test and higher mortality than in rats with noninfected pancreatitis. Intraductal injection of infected bile frequently reulted also in infected suppuration of the pancreas after 7 days.Another mechanism for infected acute pancreatitis is translocation of bacteria through the intestinal wall. Acute pancreatitis, induced by sterile bile was associated with translocation of Escherichia coli and systemic contamination two days later. Bacterial overgrowth of both aerobic and anaerobic flora was seen in the intestines, but no damage to the intestinal mucosa. Bacterial translocation was a graded response, depending on the severity of pancreatitis. Pancreatic necrosis, however, was seldom infected 7 days after induction of acute pancreatitis with sterile bile. Bacterial translocation during acute pancreatitis therefore occurs only during the first days. The results of the experiments indicate ascending irfection as the main mechanism for secondary infected pancreatitis in rats with bile-induced acute pancreatitis.

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