Dietary omega-3 supplementation exacerbates left ventricular dysfunction in an ovine model of anthracycline-induced cardiotoxicity

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dc.contributor.authorCarbone, A.
dc.contributor.authorPsaltis, P.
dc.contributor.authorNelson, A.
dc.contributor.authorMetcalf, R.
dc.contributor.authorRichardson, J.
dc.contributor.authorWeightman, M.
dc.contributor.authorThomas, A.
dc.contributor.authorFinnie, J.
dc.contributor.authorYoung, G.
dc.contributor.authorWorthley, S.
dc.date.issued2012
dc.description.abstractBACKGROUND: 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.
dc.description.statementofresponsibilityAngelo 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
dc.identifier.citationJournal of Cardiac Failure, 2012; 18(6):502-511
dc.identifier.doi10.1016/j.cardfail.2012.03.005
dc.identifier.issn1071-9164
dc.identifier.issn1532-8414
dc.identifier.orcidPsaltis, P. [0000-0003-0222-5468]
dc.identifier.orcidNelson, A. [0000-0003-0990-2548]
dc.identifier.orcidWeightman, M. [0000-0001-8451-2529]
dc.identifier.orcidFinnie, J. [0000-0003-2277-1693]
dc.identifier.urihttp://hdl.handle.net/2440/72379
dc.language.isoen
dc.publisherChurchill Livingstone Inc Medical Publishers
dc.rights© 2012 Published by Elsevier Inc.
dc.source.urihttps://doi.org/10.1016/j.cardfail.2012.03.005
dc.subjectAnimal models
dc.subjectcardiomyopathy
dc.subjectdoxorubicin, fish oil
dc.titleDietary omega-3 supplementation exacerbates left ventricular dysfunction in an ovine model of anthracycline-induced cardiotoxicity
dc.typeJournal article
pubs.publication-statusPublished

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