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Antiarrhythmic effects of free polyunsaturated fatty acids in an experimental model of LQT2 and LQT3 due to suppression of early afterdepolarizations and reduction of spatial and temporal dispersion of repolarization.
MedLine Citation:
PMID:  21459164     Owner:  NLM     Status:  Publisher    
BACKGROUND: Torsade 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. 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. METHODS AND RESULTS: In 123 Langendorff-perfused rabbit hearts, the I(Kr)-blocking drug erythromycin (E; 300μM) or veratridine (V; 0.5μM), an inhibitor of sodium channel inactivation, significantly increased monophasic ventricular action potentials (MAPs) thereby mimicking LQT2- and LQT3-syndrome. In AV-blocked hearts, eight epi- 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, resp.. Pretreatment with V led to EAD (TdP) in 39 (32) of 43 hearts. Additional treatment with ALA, DHA or EPA (10-20μM) in the LQT2 model, randomly assigned to three 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<0.01). 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. 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.
Peter Milberg; Gerrit Frommeyer; Anne Kleideiter; Alicia Fischer; Nani Osada; Günter Breithardt; Michael Fehr; Lars Eckardt
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-3-31
Journal Detail:
Title:  Heart rhythm : the official journal of the Heart Rhythm Society     Volume:  -     ISSN:  1556-3871     ISO Abbreviation:  -     Publication Date:  2011 Mar 
Date Detail:
Created Date:  2011-4-4     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101200317     Medline TA:  Heart Rhythm     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2011. Published by Elsevier Inc.
Hospital of the Westfälische Wilhelms-University, Department of Cardiology and Angiology, Division of Experimental and Clinical Electrophysiology, Münster, Germany.
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