Voluntary Wheel Running In Rats Receiving Doxorubicin

Abstract

The chemotherapy drug doxorubicin (DOX) is effective at combating cancerous cell growth and proliferation, but its dosing is limited because chronic usage can result in cardiac dysfunction with eventual heart failure. Previously, we have shown that endurance training prior to DOX administration ameliorates DOX-induced cardiac dysfunction which translates into improved DOX-tolerance in a trained organism. However, the likelihood of training during DOX treatment to prevent cardiac maladaptation has yet to be explored. Additionally, it has been shown that DOX treatment promotes a shift in cardiac myosin heavy chain (MHC) expression from the fast á-isoform to the slow â-isoform. PURPOSE To analyze the effects of voluntary wheel running on cardiac MHC composition in rats receiving DOX. METHODS Female Sprague-Dawley rats were randomly assigned to the voluntary running (n = 9) or the sedentary (n = 8) group. Following a 2-week running wheel acclimation period, animals received weekly IP injections of DOX (2.5 mg/kg) for 6 weeks. The voluntary running group had access to running wheels throughout the treatment period. Following 6 weeks of DOX, left ventricular free walls from the animals were analyzed for MHC composition using SDS-PAGE. RESULTS The week prior to DOX injections, the rats ran a mean of 10.4±5.1 km/ day, and following week 3 of DOX, animals ran a mean of 6.7±3.8 km/day (36% decrease). Following 6 weeks of treatment, animals ran a mean of 4.1±3.0 km/day (61% decrease). The voluntary exercise group expressed a mean á-MHC percentage of 75.5±9.9% which was significantly greater than the mean á-MHC percentage of 56.8±18.5% detected in sedentary animals (p = 0.01). CONCLUSIONS Increased physical activity during DOX treatment preserved contractile MHC isoform distribution in the left ventricle. This suggests that increased physical activity during DOX treatment may help protect the heart from cardiac dysfunction.