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Am J Physiol Heart Circ Physiol 287: H2241-H2251, 2004. First published July 15, 2004; doi:10.1152/ajpheart.00390.2004
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Selective decontamination of the digestive tract attenuated the myocardial inflammation and dysfunction that occur with burn injury

Jureta W. Horton,1 Jing Tan,1 D. Jean White,1 David L. Maass,1 and James A. Thomas2

1Department of Surgery and 2Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas 75390

Submitted 26 April 2004 ; accepted in final form 9 July 2004

This study examined the effects of oral antibiotics to selectively decontaminate the digestive tract (SDD) on postburn myocardial signaling, inflammation, and function. We hypothesized that antibiotic therapy to eliminate pathogens from the gastrointestinal (GI) tract would reduce myocardial inflammatory responses and improve postburn myocardial performance. Sprague-Dawley rats received polymyxin E (15 mg), tobramycin (6 mg), and 5-flucytosin (100 mg) by oral gavage twice daily for 3 days preburn and 24 h postburn. Experimental groups included 1) sham burn given vehicle (3 ml water), 2) sham plus SDD, 3) burn over 40% total body surface area (TBSA) plus SDD, and 4) burn over 40% TBSA given vehicle. All burns received lactated Ringer solution (4 mg·kg–1·%burn–1); myocardial signaling (PKC{epsilon}/p38 MAPK/NF-{kappa}B) was studied 2, 4, and 24 h postburn; and cytokine secretion (systemic and myocyte secreted cytokines, ELISA) and cardiac function were examined 24 h postburn. Vehicle-treated burn injury increased myocardial PKC{epsilon}/p38 MAPK expression, promoted NF-{kappa}B nuclear translocation, promoted TNF-{alpha}, IL-1{beta}, IL-6, and IL-10 secretion, and impaired myocardial function. SDD attenuated burn-related proinflammatory myocardial signaling, cytokine secretion, and myocardial contractile defects. Our data suggest that burn-related loss of GI barrier function and translocation of microbial products serve as upstream mediators of postburn myocardial inflammatory signaling and dysfunction.

thermal injury in rats; tumor necrosis factor-{alpha}; interleukin-1{beta}; interleukin-6; myocardial contractility; nuclear factor-{kappa}B activation; p38 mitogen-activated protein kinase activation; Toll/interleukin-1 signaling



Address for reprint requests and other correspondence: J. W. Horton, Dept. of Surgery, Univ. of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390-9160 (E-mail: jureta.horton{at}utsouthwestern.edu)




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J. Tan, D. L. Maass, D. J. White, and J. W. Horton
Effects of burn injury on myocardial signaling and cytokine secretion: possible role of PKC
Am J Physiol Regulatory Integrative Comp Physiol, February 1, 2007; 292(2): R887 - R896.
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