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1Cardiac Phenomics Laboratory, Department of Physiology and 5Murdoch Children's Research Institute, Department of Paediatrics, University of Melbourne and Department of Cardiology, Royal Children's Hospital, Parkville, Victoria; 2Department of Physiology, Monash University, Victoria; 3Division of Medical Sciences, Graduate School of Medicine, School of Health Sciences, University of Wollongong, New South Wales, Australia; 4Department of Medicine, University of Lausanne Medical School, Lausanne, Switzerland
Submitted 30 October 2008 ; accepted in final form 26 January 2009
Clinically and experimentally, a case for omega-3 polyunsaturated fatty acid (PUFA) cardioprotection in females has not been clearly established. The goal of this study was to investigate whether dietary omega-3 PUFA supplementation could provide ischemic protection in female mice with an underlying genetic predisposition to cardiac hypertrophy. Mature female transgenic mice (TG) with cardiac-specific overexpression of angiotensinogen that develop normotensive cardiac hypertrophy and littermate wild-type (WT) mice were fed a fish oil-derived diet (FO) or PUFA-matched control diet (CTR) for 4 wk. Myocardial membrane lipids, ex vivo cardiac performance (intraventricular balloon) after global no-flow ischemia and reperfusion (15/30 min), and reperfusion arrhythmia incidence were assessed. FO diet suppressed cardiac growth by 5% and 10% in WT and TG, respectively (P < 0.001). The extent of mechanical recovery [rate-pressure product (RPP) = beats/min x mmHg] of FO-fed WT and TG hearts was similar (50 ± 7% vs. 45 ± 12%, 30 min reperfusion), and this was not significantly different from CTR-fed WT or TG. To evaluate whether systemic estrogen was masking a protective effect of the FO diet, the responses of ovariectomized (OVX) WT and TG mice to FO dietary intervention were assessed. The extent of mechanical recovery of FO-fed OVX WT and TG (RPP, 50 ± 4% vs. 64 ± 8%) was not enhanced compared with CTR-fed mice (RPP, 60 ± 11% vs. 80 ± 8%, P = 0.335). Dietary FO did not suppress the incidence of reperfusion arrhythmias in WT or TG hearts (ovary-intact mice or OVX). Our findings indicate a lack of cardioprotective effect of dietary FO in females, determined by assessment of mechanical and arrhythmic activity postischemia in a murine ex vivo heart model.
polyunsaturated fatty acids; ischemia-reperfusion; Langendorff perfused hearts
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