TLR4 inactivation and rBPI21 block burn-induced myocardial contractile dysfunction

James A. Thomas, May F. Tsen, D. Jean White, Jureta W. Horton

Research output: Contribution to journalArticlepeer-review

28 Scopus citations


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 (rBPI21), a protein that binds and neutralizes endotoxin. Hearts from rBPI21-treated animals were completely protected from post-burn 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.

Original languageEnglish (US)
Pages (from-to)H1645-H1655
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Issue number4 52-4
StatePublished - Oct 2002


  • Burn injury
  • Contractile function
  • Endotoxin
  • Recombinant bactericidal/permeability-increasing protein
  • Signal transduction
  • Transgenic animals

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)


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