ORIGINAL RESEARCHRemoval of luminal content protects the small intestineduring hemorrhagic shock but is not suff i cient to preventlung injuryAngelina E. Altshuler 1 , Michael D. Richter 1 , Augusta E. Modestino 1 , Alexander H. Penn 1 ,Michael J. Heller 1,2 & Geert W. Schmid-Sch€ onbein 11 Department of Bioengineering, The Institute of Engineering in Medicine, University of California San Diego, La Jolla, California, 92093-04122 Department of Nanoengineering, The Institute of Engineering in Medicine, University of California San Diego, La Jolla, California, 92093-0412KeywordsHemorrhagic shock, lung injury, lymph,protease activity, small intestine.CorrespondenceAngelina E. Altshuler, Department ofBioengineering, The Institute of Engineeringin Medicine, University of California, SanDiego, La Jolla, CA 92093-0412.Tel: 925-765-6869Fax: 858-534-5722E-mail: aaltshul@gmail.comFunding InformationThis work was supported by the NationalInstitutes of Health GM-85072.Received: 30 August 2013; Revised: 7September 2013; Accepted: 11 September2013doi:10.1002/phy2.109Physiol Rep, 1 (5), 2013, e00109, doi:10.1002/phy2.109AbstractThe small intestine plays a key role in the pathogenesis of multiple organ fail-ure following circulatory shock. Current results show that reduced perfusionof the small intestine compromises the mucosal epithelial barrier, and theintestinal contents (including pancreatic digestive enzymes and partiallydigested food) can enter the intestinal wall and transport through the circula-tion or mesenteric lymph to other organs such as the lung. The extent towhich the luminal contents of the small intestine mediate tissue damage inthe intestine and lung is poorly understood in shock. Therefore, rats wereassigned to three groups: No-hemorrhagic shock (HS) control and HS with orwithout a f l ushed intestine. HS was induced by reducing the mean arterialpressure (30 mmHg; 90 min) followed by return of shed blood and observa-tion (3 h). The small intestine and lung were analyzed for hemorrhage, neu-trophil accumulation, and cellular membrane protein degradation. After HS,animals with luminal contents had increased neutrophil accumulation, bleed-ing, and destruction of E-cadherin in the intestine. Serine protease activitywas elevated in mesenteric lymph f l uid collected from a separate group of ani-mals subjected to intestinal ischemia/reperfusion. Serine protease activity waselevated in the plasma after HS but was detected in lungs only in animals withnonf l ushed lumens. Despite removal of the luminal contents, lung injuryoccurred in both groups as determined by elevated neutrophil accumulation,permeability, and lung protein destruction. In conclusion, luminal contentssignif i cantly increase intestinal damage during experimental HS, suggestingtransport of luminal contents across the intestinal wall should be minimized.IntroductionThe digestive track has long been associated with theprogression of shock and multiple organ dysfunction syn-drome (MODS) in intensive care units (Lillehei 1957;Robinson et al. 1966), and the small intestine in particu-lar is a major contributor to the dysfunction (Lillehei1957; Poggetti et al. 1992; Magnotti et al. 1998). Hypo-volemia from hemorrhage results in intestinal ischemiaand subsequent apoptosis of epithelial cells (Lu et al.2008). This results in epithelial shedding and loss of theattached mucin (Ikeda et al. 1998; Grossmann et al. 2002;Sheng et al. 2011; Chang et al. 2012a,b). Together themucin and epithelial tight junctions form the mucosalbarrier that is responsible for keeping the intestinal con-tents, including pancreatic digestive enzymes and digestedfood particles, compartmentalized in the intestine’slumen. Failure of the barrier as a result of ischemia allowsthe contents of the intestine to penetrate into the wall ofthe intestine and contribute to further intestinal damage(Chang et al. 2012a,b).The presence of food in the intestine is a major factorthat inf l uences the outcome of shock conditions(Bounous 1967; Bounous et al. 1967). The luminalª 2013 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf ofthe American Physiological Society and The Physiological Society.This is an open access article under the terms of the Creative Commons Attribution License,which permits use, distribution and reproduction in any medium, provided the original work is properly cited.2013 | Vol. 1 | Iss. 5 | e00109Page 1Physiological Reports ISSN 2051-817X
