Long-term effects of nafamostat and imipenem on experimental acute pancreatitis in rats.

Long-term effects of nafamostat mesylate, a protease inhibitor, and imipenem, an antibiotic, on trypsintaurocholate-induced acute pancreatitis were studied in rats. Sham-operated rats infused with a buffer solution into the pancreatic duct served as controls. Nafamostat (1 mg/kg), imipenem (10 mg/kg), or imipenem + nafamostat in saline was injected subcutaneously 0.25, 3, 24, and 48 hours after the induction of pancreatitis. In untreated rats and control rats, saline was injected at the same intervals as in the treated rats. All rats in an untreated group died within 3.5 days (median survival, 1.25 day) after the induction of pancreatitis. The 2-week survival rate was significantly (p < 0.05) improved by a combination of nafamostat and imipenem (42%), but not by nafamostat (17%), or imipenem (8%) alone. Bacterial culture at 24 hours revealed infection of necrotic pancreatic tissues and ascites by intestinal bacteria in all untreated rats but not in control rats. Bacterial counts were significantly reduced by imipenem, but not by nafamostat. In conclusion, bacterial infection occurred within 24 hours after the induction of trypsintaurocholate pancreatitis in rats. Early treatment with nafamostat + imipenem, but not nafamostat or imipenem alone, improves long-term survival.