Background: Sudden cardiac death (SCD) is the most common cause of death in the United States and in most developed countries, accounting for ~ 50% of total mortality. The most common underlying cause of SCD is “ventricular fibrillation” (VF). Several clinical trials have reported conflicting results on the benefits of omega-3 fatty acids for the prevention of lethal ventricular arrhythmias following infarction. The explanation for these inconsistent results remains to be determined.
Methods: Dogs with healed left ventricular anterior wall myocardial infarctions (MI, 3-4 weeks post- MI, n = 76) were subjected to an exercise and ischemia test to stratify animals by arrhythmia risk as VF susceptible, VF+ (n = 46) and VF resistant, VF- (n = 30). The animals were then assigned to omega-3 fatty acid ethyl esters (1-4 grams/day, n = 45) or corn-oil treatment (placebo, n = 31) for 3 months. Following treatment, arrhythmia inducibility was re-evaluated with the exercise and ischemia test. The left ventricular myocytes were isolated one week following the exercise plus ischemia test. Five age matched dogs served as controls (non-infarcted). Action potentials were recorded by perforated whole cell patch clamp studies (T= 36 ± 0.5°C) to measure the resting membrane potentials (RMP) and the action potential duration at 90% repolarization (APD90).
Results: Omega-3 treatment resulted in either sudden death or a positive exercise plus ischemia test in 5 out of 15 (33.3%) VF resistant dogs (p<0.05 vs. placebo) whereas, 4 out of 30 (13.3%) omega-3 treated VF+ dogs no longer had VF at the end of the treatment period (p>0.05 vs. placebo). In addition, 5 out of 30 (16.7%) omega-3 treated dogs VF+ had SCD (p>0.05 vs. placebo). There was no significant differences in RMP following omega-3 treatment in both VF+ and VF- animals (p>0.05 vs. placebo). The APD90 of myocytes of dogs protected from VF following omega-3 treatment was significantly shorter (p<0.05) compared to the myocytes from placebo-treated dogs and was similar to the APD90 from the myocytes of normal control (non-infarcted) dogs at both 0.5 Hz and 1 Hz stimulation frequency. The longest APD90 was observed in myocytes from VF- that developed arrhythmias after omega-3 treatment [VF(-,+)] compared to the myocytes from placebo-treated VF- or normal control animals at both 0.5 Hz and 1 Hz frequency. The prolongation of APD90 in the placebo-treated VF+ group was also associated with a significant (p<0.05 vs. control) increase in beat-to-beat variability of APD90 (quantified as SD1 and SD2), a marker of increased risk of pro-arrhythmia which was normalized after omega-3 treatment (p<0.05). There were no significant differences in the SD1 and SD2 between the placebo-treated VF- animals and control (non-infarcted) animals (p>0.05) whereas the myocytes from VF- dogs that developed arrhythmias after treatment [VF (-,+)] exhibited increased beat-to to-beat variability of APD90 than myocytes from placebo-treated VF- or normal control dogs (p<0.05).
Conclusion: Chronic treatment with omega-3 fatty acids is not anti-arrhythmic in animals known to be at risk for sudden cardiac death. In fact, chronic treatment with omega-3 fatty acids may be pro-arrhythmic.