The Ability of Omega-3 Fatty Acids to Prevent Non-Ischaemic Cardiac Damage in an Ovine Model of Doxorubicin-induced Cardiomyopathy

Abstract

Background: Doxorubicin (DOX) (Adriamycin anthracycline) is widely used as a chemotherapy agent in the treatment of various forms of cancer. However, its major clinical shortcoming is that it causes a dose dependant and irreversible non-ischaemic cardiomyopathy (NICM). Omega-3 fatty acids have cardioprotective effects, however there is conflicting data regarding its protectiveeffects against anthracycline inducedcardiomyopathy. This study evaluated the cardioprotective effects of Omega-3 fatty acids in an ovinemodel of DOX-induced NICM. Methods: 17 merino wether sheep (weight range 41–61.5 kg) received three fortnightly intracoronary infusions of 1.2mg/kg DOX. Sheep were euthanased 12 weeks later. Eight sheep received oral drenching with 23mL fish oil three times per week throughout the study, equating to 10 gOmega-3 fatty acid intake per week. The remaining sheep received olive oil placebo. Cardiovascular magnetic resonance assessment was undertaken prior to and at completion of study to quantify changes in left ventricular ejection fraction (LVEF). Results: Drenching sheep with 10 g per week Omega-3 fatty acids caused a significant increase in plasma, erythrocyte and cardiomyocyte bound levels ofOmega-3 fatty acids (p< 0.05). The mean absolute LVEF decreased by 19.4% in the Omega-3 group (from 48.6± 2.6% baseline to 29.2± 3.1% final (p= 0.0041)) and by 8.1% in the control group (42.5± 2.3% baseline to 34.4± 3.1, (p= 0.0001)). Conclusion:Dietary supplementation of Omega-3 fatty acids did not confer any cardioprotective benefits in this ovine model of DOX-induced NICM. In fact, in this study there were detrimental effects seen in LVEF.