Therapeutic Efficacy of Continuous Arterial Infusion of an Antibiotic and a Protease Inhibitor via the Superior Mesenteric Artery for Acute Pancreatitis in an Animal Model

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Abstract
The major cause of death in acute pancreatitis is severe infection owing to bacterial translocation. As a new strategy, we investigated the effects of continuous intra-arterial infusion of an antibiotic (imipenem) or protease inhibitor (nafamostat mesylate) via the superior mesenteric artery (SMA) on bacterial translocation in acute pancreatitis. Infusion of saline (group I), nafamostat mesylate (group II), or imipenem (group III) was started 6 hours after inducing acute pancreatitis in dogs by infusing autologous gallbladder bile into the main pancreatic duct. The survival rate in group III was significantly improved compared to group I (100 vs. 30% at 24 hours), and bacterial infection of the peritoneal fluid, mesenteric lymph nodes, and pancreas was completely prevented in group III. Intestinal damage assessed by light and scanning electron microscopy and by biochemical parameters (mucosal protein content and myeloperoxidase activity) was also significantly mitigated in group III, which showed milder pancreatic necrosis as well. There was little beneficial effect in preventing bacterial translocation in group II, although the survival rate at 24 hours (70%) was improved. Continuous arterial infusion of an antibiotic via the SMA is effective in mitigating intestinal mucosal damage and preventing bacterial translocation in acute pancreatitis, thereby improving survival.