A Diet Rich in Unsaturated Fatty Acids Prevents Progression Toward Heart Failure in a Rabbit Model of Pressure and Volume Overload

Background-During heart failure (HF), cardiac metabolic substrate preference changes from fatty acid (FA) toward glucose oxidation. This change may cause progression toward heart failure. We hypothesize that a diet rich in FAs may prevent this process, and that dietary omega 3-FAs have an added antiarrhythmic effect based on action potential (AP) shortening in animals with HF. Methods and Results-Rabbits were fed a diet containing 1.25% (w/w) high oleic sunflower oil (HF-omega 9, N=11), 1.25% fish oil (HF-omega 3, N=11), or no supplement (HF-control, N=8). Subsequently, HF was induced by volume and pressure overload. After 4 months, HF-parameters were assessed, electrocardiograms were recorded, and blood and ventricular tissue were collected. Myocytes were isolated for patch clamp or intracellular Ca2+-recordings to study electrophysiologic remodeling and arrhythmogenesis. Both the HF-omega 9 and the HF-omega 3 groups had larger myocardial FA oxidation capacity than HF control. The HF-omega 3 group had significantly lower mean (+/- SEM) relative heart and lung weight (3.3 +/- 0.13 and 3.2 +/- 0.12 g kg(-1), respectively) than HF control (4.8 +/- 0.30 and 4.5 +/- 0.23), and shorter QTc intervals (167 +/- 2.6 versus 182 +/- 6.4). The HF-omega 9 also displayed a significantly reduced relative heart weight (3.6 +/- 0.26), but had similar QTc (179 +/- 4.3) compared with HF control. AP duration in the HF-omega 3 group was approximate to 20% shorter due to increased I-to1 and I-K1 and triggered activity, and Ca2+-aftertransients were less than in the HF-omega 9 group. Conclusions-Dietary unsaturated FAs started prior to induction of HF prevent hypertrophy and HF. In addition, fish oil FAs prevent HF-induced electrophysiologic remodeling and arrhythmias. (Circ Heart Fail. 2012;5:376-384.)