title: Selective decontamination of the digestive tract attenuated the myocardial inflammation and dysfunction that occur with burn injury.
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 (PKCepsilon/p38 MAPK/NF-kappaB) 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 PKCepsilon/p38 MAPK expression, promoted NF-kappaB nuclear translocation, promoted TNF-alpha, IL-1beta, 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.
authors.affiliation: Dept. of Surgery, Univ. of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390-9160, USA. jureta.horton@utsouthwestern.edu
authors.forename: Jureta W
authors.initials: JW
authors.lastname: Horton
authors.forename: Jing
authors.initials: J
authors.lastname: Tan
authors.forename: D Jean
authors.initials: DJ
authors.lastname: White
authors.forename: David L
authors.initials: DL
authors.lastname: Maass
authors.forename: James A
authors.initials: JA
authors.lastname: Thomas
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002056:Burns / Q000150:complications* / Q000473:pathology / Q000503:physiopathology*; D002118:Calcium / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D041981:Gastrointestinal Tract / Q000187:drug effects / Q000382:microbiology*; D006321:Heart / Q000187:drug effects / Q000503:physiopathology*; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D009200:Myocardial Contraction; D009205:Myocarditis / Q000209:etiology / Q000473:pathology*; D032383:Myocytes, Cardiac / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D012964:Sodium / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D016207:Cytokines; D018836:Inflammation Mediators; D016328:NF-kappa B; D012964:Sodium; D002118:Calcium