The Auto‐Digestion Hypothesis: Blockade of Pancreatic Digestive Enzymes in the Lumen of the Intestine during Hemorrhagic Shock Reduces Mortality.

Our evidence shows that pancreatic digestive enzyme blockade in the intestinal lumen reduces levels of inflammatory mediators in portal veins and central circulation with reduced peripheral inflammation, tissue swelling, and multi‐organ dysfunction. No study exists to examine whether blockade of the digestive enzymes in the lumen of the intestine during acute hemorrhagic shock leads to long‐term survival. Thus we exposed mature male Wistar rats to hemorrhagic shock (mean arterial pressure reduced from ~110 to 30 – 35 mmHg for 120 min) followed by full restoration of shed blood volume (0.5 U/ml heparin). Control animals were administered at 60 min GoLytely® by direct injection (15 ml) into the lumen of the duodenum, ileum and secum. Treated animals received at 60 min or prior at the time of pressure decompensation (between 40 and 60 min) GoLytely supplemented with the pancreatic enzyme inhibitor ANGD (PNAS, 97:, 2000; 0.1 mM; 15 ml). Survival was recorded for 2 weeks until normal weight gain. Without blockade of digestive enzymes 8/9 rats died within the first 12 hours, while with blockade 8/10 rats survived. Digestive enzymes blockade at a later stage of hemorrhagic shock yields reduced survival. These results show a dramatic reduction of mortality in hemorrhagic shock induced multi‐organ failure with possible clinical utility. Supported in part by HL 67825.