School of Sport and Exercise Science, University of Northern Colorado, Greeley, CO 80639, USA.
Cancer Chemother Pharmacol. 2011 Sep;68(3):685-92. doi: 10.1007/s00280-010-1523-6. Epub 2010 Dec 5.
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 cardiac 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 cardiac 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.
Female rats were randomly assigned to control (CON), GA, DOX, GA + DOX, or exercise training during GA + DOX (EX GA + DOX). Following 56 days, cardiac function was analyzed in vivo using echocardiography and ex vivo using an isolated working heart model.
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 ventricular 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.
GA + DOX resulted in significantly impaired in vivo and ex vivo cardiac function, but exercise training during GA + DOX was cardioprotective.
阿霉素（DOX）和醋酸戈舍瑞林（GA）单独使用时，可能通过不同的机制导致心脏功能受损。然而，当 GA 和 DOX 联合使用（GA+DOX）时，与单独给予 GA 和 DOX 相比，可能会加剧心脏功能障碍。因此，本研究的第一个目的是研究 GA+DOX 对心脏功能的影响。此外，由于运动训练已被证明可以预防单独给予 GA 和 DOX 引起的心脏功能障碍，因此本研究的第二个目的是研究 GA+DOX 期间运动对心脏功能的影响。
雌性大鼠被随机分为对照组（CON）、GA 组、DOX 组、GA+DOX 组或 GA+DOX 期间的运动训练组（EX GA+DOX）。56 天后，使用超声心动图在体内和离体工作心脏模型中分析心脏功能。
与 CON 相比，GA+DOX 的二尖瓣最大和平均血流速度以及主动脉瓣最大血流速度明显降低（体内分析，P<0.05），但 EX GA+DOX 与 CON 之间没有观察到这些差异。在离体工作心脏中，GA+DOX 心脏的左心室发展压和最大压力发展和下降率与 CON 明显不同（P<0.05），但在 EX GA+DOX 中没有观察到这些差异。
GA+DOX 导致明显的体内和离体心脏功能受损，但 GA+DOX 期间的运动训练具有心脏保护作用。
