Small skin burn injury reduces cardiac tolerance to ischemia via a tumor necrosis factor alpha-dependent pathway

Background Large burns cause systemic inflammation and myocardial depression. We hypothesized that small burns affect cardiac tolerance to ischemia, and that tumor necrosis factor alpha (TNFα) signaling through endothelin-1 (ET) and nuclear factor kappa B (NFκB) are associated. Methods Mice were randomly assigned to four groups: burn (caused by boiling water on <2% of the body surface area), sham, burn + etanercept (TNFα blocker) treatment and sham + etanercept treatment. Twenty-four hours later, hearts were isolated and subjected to global ischemia followed by reperfusion. Additional hearts and burned skin lesions were sampled to evaluate expression of TNFα (immunoblotting) and endothelin-1 (radioimmunoassay). A NFκB-luciferase reporter mouse was used to evaluate NFκB activation. Results Baseline cardiac function before ischemia (BI) was only negligibly influenced by burn or etanercept, but was reduced by burn + etanercept. Burn markedly impaired post-ischemic left ventricular function and increased infarct size in comparison with sham-treated mice. Cardiac, but nut cutaneous, expression of TNFα was increased in burned mice, while cardiac NFκB and endothelin-1 were not influenced. TNFα blockade reduced the detrimental effects of burn on cardiac tolerance to ischemia. Conclusions Small cutaneous burns, that did not influence baseline heart function, impaired the tolerance to ischemia. This effect may be mediated through TNFα, but does not involve signaling through NFκB or endothelin-1.