- 作者：Angelo Carbone ; BSc ; MMedSc<sup>1sup> ; Peter J. Psaltis ; MBBS ; PhD<sup>1sup><sup> ; sup><sup>2sup> ; Adam J. Nelson ; MBBS ; BMedSc<sup>1sup> ; Robert Metcalf ; BSc ; MNutrSc ; PhD<sup>1sup> ; James D. Richardson ; MBBS<sup>1sup> ; Michael Weightman<sup>1sup> ; Anthony Thomas ; MBBS ; BSc ; MSc ; PhD<sup>3sup> ; John W. Finnie ; BVSc ; PhD ; FRCVS<sup>4sup> ; Glenn D. Young ; MBBS<sup>1sup> ; Stephen G. Worthley ; MBBS ; MD ; PhD<sup>1sup><sup> ; sup><sup>stephen.worthley@adelaide.edu.ausup>
- 关键词：Animal models ; cardiomyopathy ; doxorubicin ; fish oil
- 刊名：Journal of Cardiac Failure
- 出版年：2012
- 出版时间：June, 2012
- 年：2012
- 卷：18
- 期：6
- 页码：502-511
- 全文大小：917 K
ss=""h4"">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.ss=""h4"">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.
ss=""h4"">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.