ORIGINAL ARTICLE Effects of endurance training on combined goserelin acetate and doxorubicin treatment–induced cardiac dysfunction David S. Hydock • Traci L. Parry • Brock T. Jensen • Chia-Ying Lien • Carole M. Schneider • Reid Hayward Received: 28 July 2010 / Accepted: 5 November 2010 Ó Springer-Verlag 2010 Abstract Purpose Doxorubicin (DOX) and goserelin acetate (GA), when administered individually, can lead to impaired cardiac function via different mechanisms. Combining GA and DOX (GA ? DOX), however, could potentially exacerbate car- diac dysfunction when compared to GA and DOX treatments administered individually. Therefore, the first purpose of this study was to investigate the effects of GA ? DOX on car- diac function. Additionally, since exercise training has been shown to protect against GA- and DOX-induced cardiac dysfunction when administered individually, the second purpose of this study was to examine the effects of exercise during GA ? DOX on cardiac function. Methods Female rats were randomly assigned to control (CON), GA, DOX, GA ? DOX, or exercise training dur- ing GA ? DOX (EX GA ? DOX). Following 56 days, cardiac function was analyzed in vivo using echocardiog- raphy and ex vivo using an isolated working heart model. Results GA ? DOX had significantly lower mitral valve maximal and mean blood flow velocities and aortic valve maximal blood flow velocity than CON (in vivo analysis, P \ 0.05), but these differences were not observed between EX GA ? DOX and CON. In the isolated working heart, GA ? DOX hearts had significantly different left ventricu- lar developed pressures and maximal rates of pressure development and decline than CON (P \ 0.05), but these differences were not observed in EX GA ? DOX. Conclusions GA ? DOX resulted in significantly impaired in vivo and ex vivo cardiac function, but exercise training during GA ? DOX was cardioprotective. Keywords Anthracycline Á Cardiac function Á Echocardiography Á Estrogens Á Ovariectomy Á Physical activity Introduction Although the anthracycline antibiotic doxorubicin (DOX, trade name Adriamycin Ò ) is an effective chemotherapy drug used to treat a variety of solid tumors and systemic malig- nancies, one of its most commonly recognized side effects is cardiotoxicity, which limits its use clinically. This cardio- toxicity is most commonly attributed to myocardial oxida- tive stress that can lead to impaired cardiac performance observed immediately following, days following, weeks following, or even months to years following treatment (for review, see Ref [1]). Although DOX-induced cardiotoxicity is an overwhelming clinical concern, DOX has been shown to induce ovarian damage, which can perpetuate irreversible infertility [2–5]. In an attempt to combat DOX-induced ovarian damage, supplemental treatment with luteinizing hormone–releasing hormone (LHRH) agonists such as goserelin acetate (GA) has been shown to minimize DOX- induced sterility by suppressing gonadal function prior to and during DOX treatment [6, 7]. Consequently, once DOX treatment is complete, GA treatment is discontinued and gonadal function returns to normal [2, 8]. Although combined GA and DOX use is favorable for preserving ovarian function, there is evidence that this D. S. Hydock Á T. L. Parry Á B. T. Jensen Á C.-Y. Lien Á C. M. Schneider Á R. Hayward (&) School of Sport and Exercise Science, University of Northern Colorado, Greeley, CO 80639, USA e-mail: Reid.Hayward@unco.edu D. S. Hydock Á T. L. Parry Á B. T. Jensen Á C.-Y. Lien Á C. M. Schneider Á R. Hayward The Rocky Mountain Cancer Rehabilitation Institute, University of Northern Colorado, Greeley, CO 80639, USA 123 Cancer Chemother Pharmacol DOI 10.1007/s00280-010-1523-6