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 (TNFalpha) signaling through endothelin-1 (ET) and nuclear factor kappa B (NF kappaB) 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 (TNFalpha 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 TNFalpha (immunoblotting) and endothelin-1 (radioimmunoassay). A NF kappaB-luciferase reporter mouse was used to evaluate NF kappaB 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 TNFalpha was increased in burned mice, while cardiac NF kappaB and endothelin-1 were not influenced. TNFalpha 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 TNFalpha, but does not involve signaling through NF kappaB or endothelin-1.
Labruto
Fausto
F
Crafoord Laboratory for Experimental Surgery, Karolinska University Hospital, Stockholm, Sweden. fausto.labruto@karolinska.se
Pernow
John
J
Yang
Jangning
J
Vaage
Jarle
J
Valen
Guro
G
D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D002056:Burns / Q000378:metabolism / Q000503:physiopathology*; D002450:Cell Communication; D003326:Coronary Circulation / Q000502:physiology; D019332:Endothelin-1 / Q000378:metabolism; D015151:Immunoblotting; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017202:Myocardial Ischemia / Q000378:metabolism / Q000503:physiopathology*; D016328:NF-kappa B / Q000378:metabolism; D011897:Random Allocation; D012867:Skin / Q000293:injuries* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D019332:Endothelin-1; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha