Gut Wall Compromise in the Presence of Pancreatic Enzymes Causes Circulatory Shock


Pancreatic proteolytic enzymes (PEs) in the ischemic intestine play a central role in multisystem organ failure, which can be prevented by protease inhibition in the small intestine lumen. PEs, if allowed to circulate systemically may also result in shock. However, it is unclear whether enzyme liberation in an intestine with increased permeability alone leads to shock. To test this idea the non-ischemic rat small intestinal lumen was perfused for two hours with either (A) PEs, (B) interventions designed to increase lumenal permeability (N-acetylcysteine (NAC) + atropine + increased flow) or (C) both, and animals were observed for shock and organ failure. PEs perfused (Groups A and C) included trypsin, chymotrypsin, elastase, amylase and lipase at concentrations 2 log greater than baseline values. Group A (n=6) maintained baseline blood pressures as did other groups perfused with single enzymes alone. However all animals in Group C (n=6) developed hypotension, significant increases in gut permeability (p<0.001) and died (p<0.001). Group B (n=6) developed mild hypotension (NS) and increased gut permeability (p<0.05) compared to controls but there were no deaths. These experiments demonstrate for the first time that increased gut permeability in the presence of lumenal PEs is sufficient to induce shock. PEs, if allowed to penetrate the gut wall result in multiorgan failure and death. Supported by NIH Grant GM085072

Erik B. Kistler1,2 and Geert W. Schmid-Schonbein1
1 Department of Bioengineering
2 Department of Anesthesia, University of California, San Diego, San Diego, CA

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