Background: Torsades de pointes (TdP) are induced by early afterdepolarizations (EADs) in the presence of an increased dispersion of repolarization. Free polyunsaturated fatty acids (PUFAs) have been suggested to influence cardiac repolarization.
Objective: The purpose of this experimental study was to investigate the electrophysiologic effects of PUFAs in a model of LQT2 and LQT3.
Methods: We investigated the acute antiarrhythmic potential of α-linolenic acid (ALA), docosahexaenoic acid (DHA), and eicosapentaenoic acid (EPA) in a whole-heart model of long QT2 (LQT2) and long QT3 (LQT3) syndrome.
Results: In 123 Langendorff-perfused rabbit hearts, the I(Kr)-blocking drug erythromycin (E; 300 μM) or veratridine (V; 0.5 μM), an inhibitor of sodium channel inactivation, significantly increased monophasic ventricular action potentials (MAPs), thereby mimicking LQT2 and LQT3 syndrome. In atrioventricular-blocked hearts, 8 epicardial and endocardial MAPs demonstrated a significant increase in spatial and temporal dispersion. After lowering potassium concentration, E led to EADs and TdP in 44 and 41 of 53 hearts, respectively. Pretreatment with V led to EAD (TdP) in 39 (32) of 43 hearts. Additional treatment with ALA, DHA, or EPA (10 to 20 μM) in the LQT2 model, randomly assigned to 3 groups, suppressed EAD in 72% of ALA-treated hearts and in all hearts that were treated with EPA or DHA. This led to a reduction of TdP of 67% (ALA) and to complete abolishment of TdP in all hearts that were treated with EPA or DHA. A comparable finding was seen in V-pretreated hearts. In addition, DHA and EPA significantly shortened MAP duration and reduced spatial and temporal dispersion of repolarization (P <.01).
Conclusion: The present study showed for the first time that PUFAs are effective in preventing TdP in an experimental model of LQT2 and LQT3 syndrome due to a reversion of AP prolongation, a reduction of spatial and temporal dispersion of repolarization and a suppression of EAD. The PUFA effect is stronger in LQT2 than in LQT3 syndrome, and the antitorsadogenic effect is more remarkable with DHA and EPA as compared with ALA.
Copyright © 2011 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.