Exercise preconditioning protects against doxorubicin-induced cardiac dysfunction.
The clinical use of the chemotherapeutic drug doxorubicin (DOX) is limited due to a dose-dependent cardiotoxicity. Evidence is mounting that exercise protects against DOX-related cardiac dysfunction, and as such, it may be possible that prior endurance training promotes defense against DOX cardiotoxicity.


OBJECTIVE
To examine the effects of exercise preconditioning on acute DOX-induced cardiotoxicity, and to determine whether any observed cardioprotection was associated with myosin heavy chain (MHC) isoform alterations.


METHODS
Male Sprague-Dawley rats trained on a motorized treadmill, had access to voluntary running wheels, or remained sedentary for 10 wk prior to being injected with either saline or 10 mg.kg(-1) DOX. Left ventricular function was then assessed in vivo using transthoracic echocardiography and ex vivo using the isolated working heart at 5 and 10 d after injection. Additionally, left ventricular MHC isoform expression was analyzed as a possible mechanism to explain exercise-induced cardioprotection.


RESULTS
DOX treatment promoted significant in vivo and ex vivo cardiac dysfunction at 5 and 10 d after injection in sedentary animals, and this dysfunction was associated with an upregulation of the beta-MHC isoform. Exercise preconditioning protected against DOX-induced cardiac dysfunction at 5 and 10 d after injection by attenuating beta-MHC upregulation.


CONCLUSIONS
Endurance training prior to DOX treatment protects against acute DOX cardiotoxicity for up to 10 d, and this protection can potentially be explained by a preservation of MHC isoform distribution.
Hydock
David S
DS
School of Sport and Exercise Science, University of Northern Colorado, Greeley, CO 80639, USA.
Lien
Chia-Ying
CY
Schneider
Carole M
CM
Hayward
Reid
R
D000704:Analysis of Variance; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity*; D001795:Blood Pressure Determination; D004317:Doxorubicin / Q000633:toxicity*; D004452:Echocardiography; D006321:Heart / Q000187:drug effects*; D008297:Male; D018995:Myosin Heavy Chains / Q000097:blood; D010805:Physical Conditioning, Animal; D051381:Rats; D017207:Rats, Sprague-Dawley
D000903:Antibiotics, Antineoplastic; D004317:Doxorubicin; D018995:Myosin Heavy Chains