EFFECTS OF BURN SERUM ON MYOCARDIAL INFLAMMATION AND FUNCTION

Abstract

Large cutaneous burns are clearly recognized to produce acute myocardial contractile dysfunction. This study used a model of burn serum challenge in either primary cardiomyocyte cultures or isolated perfused hearts to examine several aspects of burn-serum-related contractile dysfunction as well as myocardial inflammatory responses. Despite the absence of detectable LPS in burn serum, pretreating isolated cells or perfused hearts with recombinant bactericidal permeability-increasing protein (rBPI21) prevented both the inflammatory cytokine cascade and the cardiac contractile dysfunction induced by burn serum treatment of myocytes or ventricular muscle preparations. Our finding that anti-TNF strategies applied to isolated myocytes or hearts before burn serum challenge prevented myocardial inflammation and contractile dysfunction suggested that LPS or LPS-like factors may require the action of second messengers such as TNF-α and IL-1β to mediate LPS-related myocardial depressant effects. Our finding that experimental approaches neutralizing circulating LPS provided cardioprotection suggested that bacterial endotoxin or LPS-like molecules contribute, in part, to burn-related myocardial contractile dysfunction.