Antiarrhythmic and electrophysiological effects of long-chain omega-3 polyunsaturated fatty acids.
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.
Dhein
Stefan
S
Clinic for Cardiac Surgery, University of Leipzig, Heart Center, Struempellstrasse 39, 04289 Leipzig, Germany. dhes@medizin.uni-leipzig.de
Michaelis
Bjela
B
Mohr
Friedrich-Wilhelm
FW
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D016880:Anisotropy; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D002302:Cardiac Output / Q000187:drug effects*; D003864:Depression, Chemical; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015118:Eicosapentaenoic Acid / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D010496:Pericardium / Q000187:drug effects; D011817:Rabbits; D016277:Ventricular Function, Left / Q000187:drug effects*; D017962:alpha-Linolenic Acid / Q000494:pharmacology
D000889:Anti-Arrhythmia Agents; D017962:alpha-Linolenic Acid; D004281:Docosahexaenoic Acids; D015118:Eicosapentaenoic Acid