Modulation of anthracycline-induced cardiotoxicity by aerobic exercise in breast cancer: current evidence and underlying mechanisms.
Modulation of anthracycline-induced cardiotoxicity by aerobic exercise in breast cancer: current evidence and underlying mechanisms.
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DOI：
10.1161/circulationaha.111.021774
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发表时间：
2011-08-02
期刊：
影响因子：
37.8
通讯作者：
Jones LW
中科院分区：
文献类型：
--
作者：
Scott JM;Khakoo A;Mackey JR;Haykowsky MJ;Douglas PS;Jones LW
众所周知，含蒽环类药物的化疗（如阿霉素）可引起剂量依赖性、进行性心脏损伤，临床表现为左心室（LV）射血分数降低，最终导致心力衰竭（HF）（表1）。不幸的是，临床上唯一可接受的减少损伤的方法是调整剂量和/或停止治疗。3因此，乳腺癌管理的一个重要挑战是最大限度地发挥阿霉素的益处，同时最大限度地减少心脏损伤。目前迫切需要新的干预措施来预防和/或治疗多柔比星引起的心脏毒性。有氧运动是一种非药物疗法，有望减轻多柔比星引起的心脏毒性。有氧运动可改善心脏收缩和舒张功能，减轻病理性心脏重塑，从而改善HF患者的运动耐量和运动期间的疲劳抵抗力。4，5与此相反，在阿霉素的背景下，有氧运动的心脏保护特性很少受到关注。尽管它缺乏“副作用”并且缺乏预防/治疗阿霉素相关心脏损伤的替代策略，但它通常不用于癌症患者。作为可能在癌症患者中使用运动的第一步，我们回顾了阿霉素诱导的心脏毒性的机制和现有的证据支持有氧运动预防/治疗心脏损伤的效用。我们还探讨了有氧运动对心脏保护作用的分子机制。这些发现对未来关于运动和多柔比星治疗在人类中的应用和有效性的研究具有意义。
Anthracycline-containing chemotherapy (eg, doxorubi-cin) is well known to cause dose-dependent, progressive cardiac damage clinically manifest as decreased left ventricular (LV) ejection fraction and, ultimately, heart failure (HF)(Table 1). 1, 2 Unfortunately, the only clinically accepted method to minimize injury is dose modification and/or therapy discontinuation. 3 An important current challenge in breast cancer management is therefore to maximize the benefits of doxorubicin while minimizing cardiac damage. Identification and examination of new interventions to prevent and/or treat doxorubicin-induced cardiotoxicity are urgently required.Aerobic exercise is a nonpharmacological therapy that promises to attenuate doxorubicin-induced cardiotoxicity. Aerobic exercise is well documented to improve systolic and diastolic function and attenuate pathological cardiac remodeling, resulting in improved exercise tolerance and resistance to fatigue during exertion in patients with HF. 4, 5 The cardioprotective properties of aerobic exercise in the context of doxorubicin have, in contrast, received scant attention. It is not generally used in cancer patients despite its lack of “side effects” and the paucity of alternative strategies to prevent/treat doxorubicin-associated cardiac damage. As a first step in the possible use of exercise in cancer patients, we reviewed the mechanisms of doxorubicininduced cardiotoxicity and the available evidence supporting the utility of aerobic exercise to prevent/treat cardiac injury. We also explored the molecular mechanisms that may underlie the cardioprotective properties of aerobic exercise. These findings have implications for future research regarding the application and effectiveness of exercise and doxorubicin treatment in humans.