title: Removal of luminal content protects the small intestine during hemorrhagic shock but is not sufficient to prevent lung injury.
abstract: The small intestine plays a key role in the pathogenesis of multiple organ failure following circulatory shock. Current results show that reduced perfusion of the small intestine compromises the mucosal epithelial barrier, and the intestinal contents (including pancreatic digestive enzymes and partially digested food) can enter the intestinal wall and transport through the circulation or mesenteric lymph to other organs such as the lung. The extent to which the luminal contents of the small intestine mediate tissue damage in the intestine and lung is poorly understood in shock. Therefore, rats were assigned to three groups: No-hemorrhagic shock (HS) control and HS with or without a flushed intestine. HS was induced by reducing the mean arterial pressure (30 mmHg; 90 min) followed by return of shed blood and observation (3 h). The small intestine and lung were analyzed for hemorrhage, neutrophil accumulation, and cellular membrane protein degradation. After HS, animals with luminal contents had increased neutrophil accumulation, bleeding, and destruction of E-cadherin in the intestine. Serine protease activity was elevated in mesenteric lymph fluid collected from a separate group of animals subjected to intestinal ischemia/reperfusion. Serine protease activity was elevated in the plasma after HS but was detected in lungs only in animals with nonflushed lumens. Despite removal of the luminal contents, lung injury occurred in both groups as determined by elevated neutrophil accumulation, permeability, and lung protein destruction. In conclusion, luminal contents significantly increase intestinal damage during experimental HS, suggesting transport of luminal contents across the intestinal wall should be minimized.
authors.affiliation: Department of Bioengineering, The Institute of Engineering in Medicine, University of California San Diego La Jolla, California, 92093-0412.
authors.forename: Angelina E
authors.initials: AE
authors.lastname: Altshuler
authors.forename: Michael D
authors.initials: MD
authors.lastname: Richter
authors.forename: Augusta E
authors.initials: AE
authors.lastname: Modestino
authors.forename: Alexander H
authors.initials: AH
authors.lastname: Penn
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Heller
authors.forename: Geert W
authors.initials: GW
authors.lastname: Schmid-Schönbein
keywords: Hemorrhagic shock; lung injury; lymph; protease activity; small intestine