Concurrent Wheel Running and Weekly Doxorubicin Treatment in the Rat: Effects on Cardiac Function

Abstract

The use of exercise as a means of battling cardiotoxicity associated with the chemotherapy drug doxorubicin is showing promise. However, questions regarding exercise's long-term protection against doxorubicin cardiotoxicity still remain. PURPOSE: To investigate the effects of concurrent voluntary wheel running and weekly doxorubicin treatment on cardiac function measured 10 or 16 weeks after treatment. METHODS: Female rats were randomly assigned to the doxorubicin group (DOX) or the control group (CON). Animals in DOX received 2.5 mg·kg-1 doxorubicin weekly for 6 weeks (15 mg·kg-1 cumulative), and animals in CON received saline injections weekly for 6 weeks. DOX and CON animals were then assigned to either wheel running (W+DOX or W+CON, respectively) or sedentary (S+DOX and S+CON, respectively) groups. W+DOX and W+CON were introduced to voluntary wheel running cages following the first injection and were allowed 24 hour per day access to the running wheels for 10 weeks (10w) or 16 weeks (16w). S+DOX and S+CON were confined to normal cage activity for 10w or 16w. Cardiac function was then assessed at 10w or 16w. RESULTS: At 10w, S+DOX had a significantly depressed fractional shortening (FS) when compared to S+CON (-25%, p<0.05), but W+DOX FS did not differ significantly from S+CON at 10w (-11%, p>0.05). S+DOX and W+DOX possessed lower maximal mitral blood flow velocities (MVmax, -53% and -33%, respectively, p<0.05) and maximal aortic blood flow velocities (AVmax, -48% and -25%, respectively, p<0.05) than S+SAL at 10w; however, MVmax and AVmax were significantly greater in W+DOX than S+DOX (p<0.05). At 16w, S+DOX had an 18% decline in FS and W+DOX had a 7% decline in FS when compared to S+CON, but these differences were not significant (p>0.05). S+DOX had a significantly reduced MVmax and AVmax when compared to S+CON at 16w (-41% and -38%, respectively, p<0.05), but W+DOX MVmax and AVmax was not found to differ from S+CON (-12% and -5%, respectively, p>0.05). CONCLUSIONS: Wheel running during and following 6 weeks of doxorubicin treatment provided cardioprotection which lasted 16 weeks.