Effects Of Low Vs. High Intensity Short-term Exercise On Doxorubicin-induced Cardiotoxicity

Abstract

Previously, we reported that short-term voluntary wheel running activity prior to doxorubicin (DOX) treatment protects against DOX cardiotoxicity. However, very little is known regarding the effect of exercise intensity on DOX-induced cardiac dysfunction. PURPOSE: To determine if short-term treadmill training at low or high intensity can attenuate the cardiac dysfunction that accompanies DOX in mature female rats. METHODS: Six month old female Sprague-Dawley rats (n=24) were randomly assigned to either sedentary (SED) or treadmill (TM) groups. TM animals participated in either a low intensity (TML) or a high intensity (TMH) progressive treadmill training protocol for 5 days. Following the activity period, animals in each group were randomly assigned to receive either a 15 mg·kg-1 cumulative dose of DOX (SED+DOX, TML+DOX, TMH+DOX) or saline (SED+SAL, TML+SAL, TMH+SAL). Left ventricle (LV) function was assessed ex vivo using an isolated working heart model 5 days post DOX exposure. RESULTS: A 44% reduction in end systolic pressure (ESP) was observed in SED+DOX when compared to SED+SAL (p<0.001). This degree of decline, however, was not observed in TML+DOX (-9%, p>0.05) and TMH+DOX (-13%, p>0.05) when compared to SED+SAL. Similarly, SED+DOX had significantly depressed LV developed pressure (-42%, p<0.001) when compared to SED+SAL, but this diminution was not observed in TML+DOX and TMH+DOX (p>0.05 vs. SED+SAL). LV maximal rate of pressure development (dP/dtmax) was significantly reduced after exposure to DOX in sedentary animals when compared to SED+SAL (p<0.001), however, prior treadmill training at either intensity TML+DOX or TMH+DOX attenuated the observed decrement induced by DOX (p>0.05). Likewise, lusitropic properties (dP/dtmin) were impaired in SED+DOX when compared to SED+SAL (p<0.01). However, this impairment was not evident in TML+DOX and TMH+DOX when compared to SED+SAL (p>0.05). CONCLUSION: Five days of treadmill preconditioning performed at either low or high intensity protected against DOX-induced cardiotoxicity possibly suggesting that cancer patients may benefit from variable exercise intensities prior to undergoing treatment with DOX.