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|Title:||Dietary omega-3 supplementation exacerbates left ventricular dysfunction in an ovine model of anthracycline-induced cardiotoxicity|
|Citation:||Journal of Cardiac Failure, 2012; 18(6):502-511|
|Publisher:||Churchill Livingstone Inc Medical Publishers|
|Angelo Carbone, Peter J. Psaltis, Adam J. Nelson, Robert Metcalf, James D. Richardson, Michael Weightman, Anthony Thomas, John W. Finnie, Glenn D. Young and Stephen G. Worthley|
|Abstract:||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 5 8) or olive oil placebo (n 5 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-3etreated 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.|
|Keywords:||Animal models; cardiomyopathy; doxorubicin, fish oil|
|Rights:||© 2012 Published by Elsevier Inc.|
|Appears in Collections:||Medicine publications|
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