Document Detail

Ultrafast sodium channel block by dietary fish oil prevents dofetilide-induced ventricular arrhythmias in rabbit hearts.
MedLine Citation:
PMID:  18676685     Owner:  NLM     Status:  MEDLINE    
Several epidemiologic and clinical studies show that following myocardial infarction, dietary supplements of omega-3 polyunsaturated fatty acids (omega3FA) reduce sudden death. Animal data show that omega3FA have antiarrhythmic properties, but their mechanisms of action require further elucidation. The effects of omega3FA supplementation were studied in female rabbits to analyze whether their antiarrhythmic effects are due to a reduction of triangulation, reverse use-dependence, instability, and dispersion (TRIaD) of the cardiac action potential (TRIaD as a measure of proarrhythmic effects). In Langendorff-perfused hearts challenged by a selective rapidly activating delayed rectifier potassium current inhibitor that has been shown to exhibit proarrhythmic effects (dofetilide; 1 to 100 nM), omega3FA pretreatment (30 days; n=6) prolonged the plateau phase of the monophasic action potential; did not slow the terminal fast repolarization; reduced the dofetilide-induced prolongation of the action potential duration; reduced dofetilide-induced triangulation; and reduced dofetilide-induced reverse use-dependence, instability of repolarization, and dispersion. Dofetilide reduced excitability in omega3FA-pretreated hearts but not in control hearts. Whereas torsades de pointes (TdP) were observed in five out of six in control hearts, none were observed in omega3FA-pretreated hearts. Docosahexaenoic acid (DHA) inhibited the sodium current with ultrafast kinetics. Dietary omega3FA supplementation markedly reduced dofetilide-induced TRIaD and abolished dofetilide-induced TdP. Ultrafast sodium channel block by DHA may account for the antiarrhythmic protection of the dietary supplements of omega3FA against dofetilide-induced proarrhythmia observed in this animal model.
K S Dujardin; B Dumotier; M David; M Guizy; C Valenzuela; L M Hondeghem
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-08-01
Journal Detail:
Title:  American journal of physiology. Heart and circulatory physiology     Volume:  295     ISSN:  0363-6135     ISO Abbreviation:  Am. J. Physiol. Heart Circ. Physiol.     Publication Date:  2008 Oct 
Date Detail:
Created Date:  2008-10-08     Completed Date:  2008-12-05     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100901228     Medline TA:  Am J Physiol Heart Circ Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  H1414-21     Citation Subset:  IM    
Heilig Hart Kliniek, Division of Cardiovascular Diseases, Roeselare, Belgium.
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MeSH Terms
Action Potentials
Anti-Arrhythmia Agents / administration & dosage,  pharmacology*
Disease Models, Animal
Docosahexaenoic Acids / administration & dosage,  pharmacology*
Heart Conduction System / drug effects*,  metabolism,  physiopathology
Sodium Channel Blockers / administration & dosage,  pharmacology*
Sodium Channels / drug effects*,  metabolism
Torsades de Pointes / chemically induced,  metabolism,  physiopathology,  prevention & control*
Reg. No./Substance:
0/Anti-Arrhythmia Agents; 0/Phenethylamines; 0/Sodium Channel Blockers; 0/Sodium Channels; 0/Sulfonamides; 115256-11-6/dofetilide; 25167-62-8/Docosahexaenoic Acids

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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