Role of Late Sodium Channel Current Block in the Management of Atrial Fibrillation
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REVIEW ARTICLE
Role of Late Sodium Channel Current Block in the Management of Atrial Fibrillation Alexander Burashnikov & Charles Antzelevitch
# Springer Science+Business Media New York 2012
Abstract The anti-arrhythmic efficacy of the late sodium channel current (late INa) inhibition has been convincingly demonstrated in the ventricles, particularly under conditions of prolonged ventricular repolarization. The value of late INa block in the setting of atrial fibrillation (AF) remains poorly investigated. All sodium channel blockers inhibit both peak and late INa and are generally more potent in inhibiting late vs. early INa. Selective late INa block does not prolong the effective refractory period (ERP), a feature common to practically all anti-AF agents. Although the late INa blocker ranolazine has been shown to be effective in suppression of AF, it is noteworthy that at concentrations at which it blocks late INa in the ventricles, it also potently blocks peak INa in the atria, thus causing rate-dependent prolongation of ERP due to development of post-repolarization refractoriness. Late INa inhibition in atria is thought to suppress intracellular calcium (Cai)-mediated triggered activity, secondary to a reduction in intracellular sodium (Nai). However, agents that block late INa (ranolazine, amiodarone, vernakalant, etc) are also potent atrial-selective peak INa blockers, so that the reduction of Nai loading in atrial cells by these agents can be in large part due to the block of peak INa. The impact of late INa inhibition is reduced by the abbreviation of the action potential that occurs in AF patients secondary to electrical remodeling. It stands to reason that selective late INa block may contribute more to inhibition of Cai-mediated triggered activity responsible for initiation of AF in clinical pathologies associated with a prolonged atrial APD (such as
long QT syndrome). Additional studies are clearly needed to test this hypothesis. Keywords Atrial fibrillation . Late sodium channel current . Ranolazine . Action potential . Pharmacology
Introduction Specific inhibition of late sodium channel current (late INa) can effectively suppress ventricular arrhythmias, particularly under conditions of prolonged ventricular repolarization (such as long QT syndrome and heart failure) [1–5]. These anti-arrhythmic actions of selective late INa inhibition are largely due to a reduction of intracellular calcium (Cai) loading, secondary to a decrease of intracellular sodium (Nai). Augmented late INa may significantly contribute to Nai loading, which brings calcium into the cell via reverse mode of sodium-calcium exchange. The electrophysiology and pharmacology of late INa as well as the antiarrhythmic benefit of its inhibition have been studied mostly in ventricles. The value of block of late INa for the suppression of atrial fibrillation (AF) remains poorly investigated. This review examines available data relative to the electrophysiology, pharmacology, and anti-AF ability of late I Na inhibition.
Electrophysiology
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