Heat stress protects against electrophysiological damages induced by acutedoxorubicin exposure in isolated rat hearts

The use of anthracycline antibiotics as anticancer agents is limited by the ir cardiac toxicity. Heat stress (HS) is known to confer protection against various myocardial injuries such as ischemia-reperfusion induced damage. T his cardioprotective mechanism is associated with an increase in endogenous antioxidative defenses and heat stress proteins (HSPs) synthesis. The aim of this study was thus to investigate whether HS could protect against acut e doxorubicin cardiotoxicity using the isolated rat heart model. Rats were either heat stressed (42 degreesC for 15 min) or sham anesthetize d. 24 h later, their hearts were isolated and retrogradely perfused at cons tant flow. Following 30-min of stabilization, hearts were perfused during 7 0 min with modified-Krebs solution containing 6 mg/1 doxorubicin. Control h earts were perfused under identical conditions but without doxorubicin. Dif ferent hemodynamic and electrophysiological parameters were assessed in hea rts from the four experimental groups. Doxorubicin exposure decreased left ventricular developed pressure (approxi mately -60% of baseline) and increased coronary perfusion pressure (approxi mately +230% of baseline). Prior HS did not modify these effects. Incidence of ventricular fibrillation (VF) was significantly enhanced by doxorubicin exposure (66% vs 0% in control group). Moreover, the ventricular action po tential duration (APD) was significantly shortened in the presence of doxor ubicin. Prior HS prevented both increase in VF incidence and shortening of APD. We conclude that prior heat stress protects myocardium against electrophysi ological injury, but not against hemodynamic damage, induced by acute doxor ubicine exposure. Further investigations are required to elucidate the prec ise mechanisms involved in this effect.