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Hayward, Reid

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In recent decades cancer survivorship has steadily increased; however, the adverse side effects associated with chemotherapy treatment can diminish a patient’s overall quality of life. One of the most effective and widely used chemotherapeutic agents is doxorubicin (DOX). Though highly effective, its use is limited by a dose-dependent cardiotoxicity. While it is known that exercise preconditioning with endurance training models provide a cardioprotective effect to DOX treatment, little focus has been placed on the effects of a resistance training (RT) model on DOX-induced cardiac dysfunction. The purpose of the study was to determine the effects of a 12-week RT model on DOX-induced cardiac dysfunction to determine if any cardioprotective effects are a result of a reduction in lipid peroxidation and to determine if any cardioprotective effects are a result of a preservation of the cardiac myosin heavy chain (MHC) isoform distribution. Ten-week-old male Sprague-Dawley rats were randomly selected to undergo 12 weeks of RT or remain sedentary (SED). Twenty-four hours following the completion of the exercise training or sedentary period, animals received a 12.5 mg/kg bolus intraperitoneal injection of DOX or a bolus intraperitoneal injection of 0.9% saline. Five days following injection, animals were sacrificed. Cardiac function was assessed both in vivo and ex vivo and the left ventricle tissue was used to assess lipid peroxidation, as measured by malondialdehyde (MDA) + 4-hydroxyalkenal (HAE) and percentage of β-MHC. The DOX treatment induced cardiac dysfunction when measured both in vivo and ex vivo. The RT provided a cardioprotective effect, evident by significant increases in end systolic pressure, left ventricular developed pressure, and the maximal rate of developed pressure. No significant difference existed between RT+DOX and SED+DOX in lipid peroxidation; however, RT did attenuate the α- to β-MHC shift that occurs with DOX treatment. These data suggest that 12 weeks of the RT model used provided cardioprotection against DOX-induced cardiac dysfunction and may be a result of preservation of the cardiac MHC isoform distribution.


Doxorubicin, Resistance Training


97 pages

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