TLR4 inactivation and rBPI(21) block burn-induced myocardial contractile dysfunction.
Both large burns and severe gram-negative sepsis are associated with acute myocardial contractile dysfunction. Because others have reported that burn injury may be followed by transient endotoxemia, we hypothesized that bacterial endotoxin induces contractile impairment after burn trauma. We tested this hypothesis in two rodent models. In each model, postburn myocardial contractility was assessed using Langendorff preparations of excised hearts. In the first model, mice expressing either a mutant form of or no Toll-like receptor 4 (TLR4), a critical element of the mammalian endotoxin receptor, were resistant to postburn myocardial contractile dysfunction. In the second model, starting 30 min or 4 h after burn injury, rats were infused with recombinant bactericidal/permeability-increasing protein (rBPI(21)), a protein that binds and neutralizes endotoxin. Hearts from rBPI(21)-treated animals were completely protected from postburn contractile impairment. Because burn-induced contractile dysfunction can be prevented either by blocking signaling through the endotoxin receptor or by neutralizing circulating LPS, bacterial endotoxin may contribute to impaired myocardial contractility after burn injury.
Thomas
James A
JA
Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas 75390, USA. James.Thomas@UTSouthwestern.edu
Tsen
May F
MF
White
D Jean
DJ
Horton
Jureta W
JW
D000818:Animals; D023181:Antimicrobial Cationic Peptides; D001798:Blood Proteins / Q000235:genetics*; D002056:Burns / Q000503:physiopathology*; D002306:Cardiac Volume / Q000502:physiology; D003326:Coronary Circulation / Q000502:physiology; D004195:Disease Models, Animal; D029721:Drosophila Proteins; D019446:Endotoxemia / Q000503:physiopathology; D005260:Female; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D008565:Membrane Proteins; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009200:Myocardial Contraction / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011956:Receptors, Cell Surface / Q000235:genetics*; D015398:Signal Transduction / Q000502:physiology; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors
D023181:Antimicrobial Cationic Peptides; D001798:Blood Proteins; D029721:Drosophila Proteins; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D011956:Receptors, Cell Surface; C495347:Tlr4 protein, rat; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; C021623:bactericidal permeability increasing protein