Inhibition of intestinal proteases decreases cellular activation in SAO shock

Splanchnic arterial occlusion (SAG) shock is accompanied by upregulated levels of cellular activation. Pancreatic proteases as well as proteolytically derived substances may constitute primary activators, turning the small intestine into a production site for activators. The pathophysiological role of intestinal proteases in rat's SAO shock was investigated. Duodenum and terminal ileum were cannulated with polyethylene tubings, and the intestine was flushed with saline. Using a peristaltic pump, the intestine was continuously circulated by 50 ml of saline with/without 10 mg of protease inhibitor, Nafamostat mesilate (FUT-175). SAO shock was induced by clamping the superior mesenteric and celiac arteries for 100 min, followed by reperfusion. Rats in FUT-175 perfused group had significantly lower production of activator, measured by pseudopod formation on naive donor leukocytes exposed to portal venous plasma film shocked animals (0.01). Inhibition of intestinal proteases could keep the mean arterial pressure 89% of baseline in average. These results indicate intestinal proteases play an important role in the production of the primary activators for circulating leukocytes and endothelial cells in SAO shock.