Protease inhibition in the intestinal lumen: attenuation of systemic inflammation and early indicators of multiple organ failure in shock

Shock
Hiroshi MitsuokaGeert W Schmid-Schönbein

Abstract

Our recent evidence suggests that pancreatic digestive enzymes in the lumen of the intestine may play a major role in the production of cardiovascular stimulatory factors during splachnic artery occlusion and reperfusion. These stimulators are detected in plasma, but their origin and mechanism of production has remained uncertain. We examine here in the rat the role of pancreatic enzymes with and without administration of a serine protease inhibitor (FOY) into the lumen of the small intestine during splanchnic artery occlusion (90 min) and reperfusion (120 min). In the presence of pancreatic enzyme inhibition in the lumen of the intestine, there is significantly enhanced survival rate, lower levels of inflammatory mediator production, the femoral artery blood pressure is maintained close to control levels, and there are significantly lower levels of cell activators in plasma. These results support the hypothesis that pancreatic enzymes may escape across the brush border barrier during intestinal ischemia and thereby initiate the production of a powerful set of cytotoxic mediators. Blockade of pancreatic enzymes in the lumen of the intestine may be a tool to interfere with inflammation and early indicators of multiorgan failure.

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Citations

Aug 31, 2013·Annals of Biomedical Engineering·Geert W Schmid-Schönbein, Marisol Chang
Oct 14, 2003·Surgery·Florian FitzalGeert W Schmid-Schönbein
Oct 20, 2004·Annals of Surgery·David B CohenEdwin A Deitch
May 13, 2008·The Journal of Trauma·Luciana Borsoi MoraesDario Birolini
Jan 25, 2013·Science Translational Medicine·Frank A DeLanoGeert W Schmid-Schönbein
Jul 13, 2006·Annual Review of Biomedical Engineering·Geert W Schmid-Schönbein
Jun 2, 2011·Srpski arhiv za celokupno lekarstvo·Maja SurbatrovićNikola S Filipović
Dec 13, 2007·World Journal of Surgery·Anubhav MittalJohn A Windsor
Apr 10, 2012·Transplantation Proceedings·Y-T LeeG W Schmid-Schönbein
Nov 28, 2007·International Immunopharmacology·Geert W Schmid-Schönbein
Dec 31, 2015·Shock·Angelina E AltshulerGeert W Schmid-Schönbein
May 1, 2019·Journal of Cardiovascular Pharmacology and Therapeutics·Federico AlettiErik B Kistler
Feb 9, 2018·Cardiology in Review·Hossein TabrizianiWilliam H Frishman
Apr 4, 2018·Journal of Lipids·Xingxuan He, Edward H Schuchman
Apr 5, 2005·Microcirculation : the Official Journal of the Microcirculatory Society, Inc·Geert W Schmid-Schönbein, Tony E Hugli
Apr 28, 2004·The American Journal of Pathology·Henrique S RosárioGeert W Schmid-Schönbein

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