Antiarrhythmic and electrophysiological effects of long-chain ω-3 polyunsaturated fatty acids

Abstract

Recent studies indicate that a diet enriched in omega-3 polyunsaturated fatty acids may prevent sudden cardiac death. The goal of the present study was to elucidate how omega-3 polyunsaturated fatty acids such as docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), and alpha-linolenic acid (ALA; 1-20 microM) may affect the cardiac activation and repolarization pattern. For this reason, DHA, EPA or ALA was infused in spontaneously beating isolated rabbit heart (Langendorff technique) and subjected to 256 electrodes epicardial mapping. All compounds exhibited a negative inotropic and chronotropic effect. EPA and ALA, but not DHA, prolonged QTc. The dispersion was enhanced at higher concentrations (>5 microM) by DHA and less (or not affected) by the others. The total activation time, reflecting ventricular conduction, was prolonged predominantly by DHA and to a lower extent by the other drugs. Atrioventricular conduction time was slowed only by DHA and EPA. To analyze of the pattern of activation, we determined the timepoint of activation as t(dU/dt(min)) for all 256 electrodes. The beat-to-beat similarity of these patterns was moderately reduced by all drugs. Regarding antiarrhythmic activity we found that the threshold for elicitation of a ventricular extrasystole was concentration-dependently enhanced by DHA and EPA, but not by ALA. DHA dose-dependently reduced longitudinal propagation velocity V(L) and to a lower extent transverse velocity V(T). Anisotropy was not significantly changed. EPA and ALA did not exhibit a systematic effect on V(L) or V(T). These results clearly demonstrate that DHA, EPA, and ALA exhibit direct electrophysiological effects with different profiles.