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Proteolytically‐derived inflammatory peptides from the bowel may circulate systemically in shock

Small bowel malperfusion and increased permeability may be key pathologic events in shock, allowing gut‐derived inflammatory peptides systemic access. Proteolytically formed as part of normal digestion, the peptides do not normally cross the mucosal barrier but may do so in shock. To test this idea, rats were subjected to hemorrhagic shock (35 mmHg for 100 min) with laparotomy, and saline or the protease inhibitor nafamostat mesilate was injected into the small bowel. Control animals were subjected to laparotomy without shock. Fluorescently labeled casein was injected into the small bowel to determine the ability of proteolytically generated peptides to reach the systemic circulation. Permeability significantly increased after ischemia in all shock groups compared to controls as assessed by casein fluorescence in the mesenteric microcirculation and in plasma (p<0.01). Nafamostat mesilate decreased permeability in the microcirculation and systemically (p<0.01). These results demonstrate that in an experimental model of hemorrhagic shock, bowel permeability is significantly increased to proteolytically derived peptides, and is mitigated by enteral protease inhibition. Inflammatory peptides from the bowel may reach the systemic circulation and contribute to the pathophysiology of gut‐derived circulatory shock. Supported by GM85072, and the ASCCA/FAER/Hospira Physician Scientist Award.