Dietary omega-3 fatty acids and susceptibility to ventricular fibrillation: lack of protection and a proarrhythmic effect.

BACKGROUND Recent clinical studies that evaluated the effects of supplemental omega-3 polyunsaturated fatty acids (n-3 PUFAs) on sudden cardiac death have yielded conflicting results. Our aim was to clarify this issue using an established and clinical relevant canine model of sudden cardiac death. METHODS AND RESULTS Susceptibility to ventricular fibrillation (VF) was evaluated using a 2-minute left circumflex artery occlusion during the last minute of an exercise test in 76 dogs (from 2 independent studies) with healed myocardial infarctions (MI); 44 developed VF (susceptible, VF+), whereas 32 did not (resistant, VF-). These dogs were then randomly assigned to either placebo (1 g/d, corn oil; 15 VF+, 11 VF-) or n-3 PUFA (1-4 g/d, docosahexaenoic acid+eicosapentaenoic acid ethyl esters, 29 VF+, 21 VF-) groups. Seven sham (no-MI) dogs were also treated with n-3 PUFA (4 g/d). After treatment (3 months), the exercise+ischemia test was repeated. Dietary n-3 PUFAs produced significant (P<0.01) increases in red blood cell and left ventricular n-3 PUFA levels. Nine post-MI (5 placebo versus 4 n-3 PUFA) and 2 sham dogs died suddenly during the 3-month treatment period. The n-3 PUFA treatment failed to prevent arrhythmias in VF+ dogs (decreased in 27% placebo versus 24% n-3 PUFA, P=0.5646) but induced VT/VF in VF- animals (n-3 PUFA 33% versus placebo 0%, P=0.0442). CONCLUSIONS Despite large increases in cardiac tissue n-3 PUFA content, dietary n-3 PUFAs did not prevent ischemia-induced VF and actually increased arrhythmia susceptibility in both noninfarcted and low-risk post-MI dogs.