Blockade of Pancreatic Digestive Proteases in Severe Hemorrhagic Shock Enhances Long‐term Survival Rate

Abstract

Our evidence suggests that the inflammation encountered in physiological shock may involve pancreatic digestive enzymes in the intestine. Once digestive enzymes breach the mucosal barrier they generate inflammation and organ dysfunction. Blockade of digestive enzymes in the intestine with protease inhibitors reduces inflammation. But no long‐term studies have tested the utility of pancreatic protease blockade as a measure to reduce multi‐organ failure and enhance survival. We exposed mature rats to acute hemorrhagic shock (30 mmHg mean arterial pressure for 120 min) by hemorrhage from the femoral artery followed by an observation period of two weeks until complete recovery and normal whole weight gain. Blockade of the digestive serine proteases after 60 min of hypotension in the lumen of the small intestine (tranexamic acid, 0.3 mM, in polyethylene glycol‐3350, 60 g/L) from the duodenum to the cecum by injection of equal aliquots directly into the intestinal lumen (~every 5cm with a total of 15 ml solution) lead to increase in survival rate (7/7) as compared without enzyme blockade (2/7; P<0.01). The treated but no untreated rat had low levels of tissue damage in several organs. These results showed a significant protection against multi‐organ failure by intraluminal blockade of digestive enzymes in the small intestine after severe hypotension.(Supported by an unrestricted gift from Leading Ventures)