Acute Exercise Protects Against Doxorubicin Cardiotoxicity

Abstract

Numerous methods have been used to minimize the cardiotoxic effects of the chemotherapeutic agent doxorubicin (DOX), and most have had limited success. Chronic endurance exercise has been shown to protect against DOX cardiotoxicity, but little is known regarding the effects of acute exercise on DOX-induced cardiac dysfunction. Purpose. The purpose of this study was to determine the effects of a single bout of acute endurance exercise on the cardiac dysfunction associated with DOX treatment. Methods. Male Sprague-Dawley rats either performed an acute exercise bout on a motorized treadmill for 60 minutes at a maximal speed of 25 m/min with a 5% grade (EX) or remained sedentary (SED) 24 hours before receiving either a 15-mg/kg DOX bolus dose or saline (SAL). Cardiac function was then analyzed 5 days post injection using a Langendorff isolated perfused heart model. In addition, myocardial lipid peroxidation was analyzed as an indicator of oxidative stress. Results. Doxorubicin treatment alone (SED+DOX) promoted a significant decline in end-systolic pressure (—35%), left ventricular developed pressure (—59%), and the maximal rate of left ventricular pressure development (—43%) as well as a 45% increase in lipid peroxidation products when compared with SED+SAL ( P < .05). Acute exercise 24 hours before DOX treatment, however, had a cardioprotective effect, as end-systolic pressure, left ventricular developed pressure, and the maximal rate of left ventricular pressure development were significantly higher in EX+DOX compared with SED+DOX ( P < .05) and EX+DOX had similar levels of lipid peroxidation products as SED+SAL Conclusions. An acute exercise bout performed 24 hours before DOX treatment protected against cardiac dysfunction, and this exercise-induced cardioprotection may partly be explained by a reduction in the generation of reactive oxygen species.