Academic Journal

Ultrafast sodium channel block by dietary fish oil prevents dofetilide-induced ventricular arrhythmias in rabbit hearts.

التفاصيل البيبلوغرافية
العنوان: Ultrafast sodium channel block by dietary fish oil prevents dofetilide-induced ventricular arrhythmias in rabbit hearts.
المؤلفون: Dujardin, K. S., Dumotier, B., David, M., Guizy, M., Valenzuela, C., Hondeghem, L. M.
المصدر: American Journal of Physiology: Heart & Circulatory Physiology; Oct2008, Vol. 295 Issue 4, pH1414-H1421, 8p, 1 Chart, 4 Graphs
مصطلحات موضوعية: MYOCARDIAL infarction, CORONARY disease, SUDDEN death, UNSATURATED fatty acids, ARRHYTHMIA, SODIUM channels
مستخلص: Several epidemiologic and clinical studies show that following myocardial infarction, dietary supplements of ω-3 polyunsaturated fatty acids (ω3FA) reduce sudden death. Animal data show that ω3FA have antiarrhythmic properties, but their mechanisms of action require further elucidation. The effects of ω3FA 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), ω3FA 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 ω3FA-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 ω3FA-pretreated hearts. Docosahexaenoic acid (DHA) inhibited the sodium current with ultrafast kinetics. Dietary ω3FA 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 ω3FA against dofetilide-induced proarrhythmia observed in this animal model. [ABSTRACT FROM AUTHOR]
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قاعدة البيانات: Complementary Index
الوصف
تدمد:03636135
DOI:10.1152/ajpheart.01219.2007