Abstract
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 (PKCε/ p38 MAPK/NF-κB) 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 PKCε/p38 MAPK expression, promoted NF-κB nuclear translocation, promoted TNF-α, IL-1β, 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.
Original language | English (US) |
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Pages (from-to) | H2241-H2251 |
Journal | American Journal of Physiology - Heart and Circulatory Physiology |
Volume | 287 |
Issue number | 5 56-5 |
DOIs | |
State | Published - Nov 2004 |
Keywords
- Interleukin-1β
- Interleukin-6
- Myocardial contractility
- Nuclear factor-κB activation
- Thermal injury in rats
- Toll/interleukin-1 signaling
- Tumor necrosis factor-α
- p38 mitogen-activated protein kinase activation
ASJC Scopus subject areas
- Physiology
- Cardiology and Cardiovascular Medicine
- Physiology (medical)