Cardiorespiratory Capacity and Body Composition are Improved with Concomitant Moderate Intensity or High-intensity Interval Training During Doxorubicin Treatment

Abstract

Doxorubicin (DOX) is a highly effective chemotherapeutic agent used to treat a variety of solid tumor malignancies including breast cancer. However, following DOX treatment breast cancer patients often suffer from reduced cardiorespiratory capacity and weight gain with increased body fat. These adverse changes following DOX treatment increase the risk of developing cardiovascular disease, thus, increasing patient mortality. In this regard, exercise has been shown to be effective in improving cardiorespiratory capacity and body composition. Therefore, using a clinically translational rodent model of DOX treatment we determined whether participation in moderate intensity aerobic training or high intensity interval training (HIIT) during treatment is sufficient to prevent these adverse effects. The DOX dosing protocol was administered in adult female Sprague-Dawley rats following a standard clinical treatment regimen (i.e., intravenous infusion of DOX once every 3 weeks for 4 total cycles, cumulative dose of ~160 mg/m2). Rats prescribed exercise training followed current exercise guidelines for cancer patients. Moderate exercise consisted of treadmill running at ~70% VO2max 1 hour/day 3x/week. HIIT consisted of 4x4 minute bouts of running at ~90% VO2max 3x/week. Dependent measures were assessed prior to the initiation of DOX treatment and one-week following the last cycle. Similar to patients, DOX reduced cardiorespiratory capacity and increased fat mass in sedentary rats. However, moderate intensity exercise and HIIT improved exercise tolerance, reduced fat mass and increased lean mass in DOX treated rats. These findings mimic the clinical effects of DOX on cardiorespiratory capacity and body composition in breast cancer patients and demonstrate that exercise training during treatment can reduce these negative effects of DOX chemotherapy. Funding NIH R01 HL144858 This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.