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 ischemiainduced VF and actually increased arrhythmia susceptibility in both noninfarcted and low-risk post-MI dogs.