Dietary Omega-3 Supplementation Exacerbates Left Ventricular Dysfunction in an Ovine Model of Anthracycline-Induced Cardiotoxicity
Dietary Omega-3 Supplementation Exacerbates Left Ventricular Dysfunction in an Ovine Model of Anthracycline-Induced Cardiotoxicity
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DOI：
10.1016/j.cardfail.2012.03.005
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发表时间：
2012-06-01
影响因子：
6
通讯作者：
Worthley, Stephen G.
中科院分区：
文献类型：
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作者：
Carbone, Angelo;Psaltis, Peter J.;Worthley, Stephen G.
背景：累积剂量依赖性非缺血性心肌病（NICM）仍然是使用某些化疗药物的重大风险。在这种情况下，已经在啮齿动物和蒽环类药物毒性体外模型中研究了 omega-3 多不饱和脂肪酸 (PUFA) 的心脏保护潜力，但结果相互矛盾。本研究评估了在蒽环类药物诱导的 NICM 大型动物模型中预防性补充 omega-3 PUFA 的情况。方法和结果：美利奴羊被随机分配口服 omega-3 PUFA（鱼油；n = 8）或橄榄油安慰剂（n = 9），然后开始重复冠状动脉内输注阿霉素 (DOX) 以诱导心脏功能障碍。 DOX 累积剂量为 3.6 mg/kg。最终 DOX 暴露后，继续浸泡 12 周。尽管组织中 omega-3 PUFA 水平显着增加（与安慰剂相比，P < .05），但 omega-3 治疗的绵羊比安慰剂动物表现出更大的蒽环类心脏毒性迹象，包括左心室扩张和射血分数更大下降（P < .05），尽管两组的心肌纤维化负担相似。结论：膳食摄入 omega-3 PUFA 无法预防甚至可能加剧 DOX 引起的心脏毒性。化疗期间临床使用 omega-3 补充剂应推迟，直至获得有关蒽环类药物暴露期间脂肪酸与心肌之间相互作用机制的更多信息。 （《心脏衰竭杂志》2012 年；18：502-511）
Background: Cumulative dose-dependent nonischemic cardiomyopathy (NICM) remains a significant risk with the use of some chemotherapeutic agents. In this context, omega-3 polyunsaturated fatty acids (PUFA) have been investigated for their cardioprotective potential in rodent and in vitro models of anthracycline toxicity, with conflicting results. This study evaluated prophylactic omega-3 PUFA supplementation in a large-animal model of anthracycline-induced NICM.Methods and Results: Merino sheep were randomized to oral drenching with omega-3 PUFA (fish oil; n = 8) or olive oil placebo (n = 9) 3 weeks before commencing repeated intracoronary infusions of doxorubicin (DOX) to induce cardiac dysfunction. Cumulative DOX dose was 3.6 mg/kg. Drenching was continued for 12 weeks after final DOX exposure. Despite significant increases in tissue omega-3 PUFA levels (P < .05 vs placebo), omega-3 treated sheep displayed greater signs of anthracycline cardiotoxicity than placebo animals, consisting of left ventricular dilatation and a greater decline in ejection fraction (P < .05), although myocardial fibrosis burden was similar in both groups.Conclusions: Dietary intake of omega-3 PUFA fails to prevent and may indeed exacerbate DOX-induced cardiotoxicity. Clinical use of omega-3 supplementation during chemotherapy should be deferred until more information is available regarding the mechanisms of interaction between fatty acids and the myocardium during anthracycline exposure. (J Cardiac Fail 2012;18:502-511)