Exercise training mitigates anthracycline‐induced chronic cardiotoxicity in a juvenile rat model

Abstract

Childhood cancer survivors are at greater risk of cardiovascular complications once they reach adulthood. Anthracyclines may be a major contributor to these delayed-onset complications, yet their use continues because of favorable clinical outcomes. Exercise has been shown to protect against anthracycline cardiotoxicity, yet it is unclear whether exercise can protect against delayed-onset cardiotoxicity when treatment is initiated in childhood. The aim of the present study was to determine if exercise training provides cardioprotection in a juvenile rat model of delayed-onset anthracycline cardiotoxicity. At 25 days of age, male Sprague-Dawley rat pups were subjected to a treatment regimen with the anthracycline doxorubicin (DOX). Pups received DOX at 2 mg/kg on 7 consecutive days (cumulative dose 14 mg/kg) or saline as a control. At the time DOX treatment began, pups remained sedentary or were allowed to voluntarily exercise. Ten weeks after the initiation of exercise, cardiac function was assessed both in vivo and ex vivo. DOX treatment stunted normal growth and significantly impaired cardiac function. While voluntary exercise did not offset changes in the growth curve, it did provide significant cardioprotection against DOX-induced cardiotoxicity. Exercise training, initiated at the time treatment begins, can protect against delayed-onset anthracycline-induced cardiotoxicity in adult rats that were treated with anthracyclines as juveniles.