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• W2149106024 abstract "Pharmacological management of atrial fibrillation (AF) remains an important unmet medical need. Because available drugs for rhythm control of AF are often associated with a significant risk for development of ventricular arrhythmias or extracardiac toxicity, recent drug development has focused on agents that are atrial selective. Inhibition of the ultrarapid delayed rectifier potassium current (IKur), a current exclusive to atria, is an example of an atrial-selective approach. Recent studies, however, have shown that loss-of-function mutations in KCNA5, the gene that encodes KV1.5, the α subunit of the IKur channel, is associated with the development of AF and that inhibition of IKur can promote the induction of AF in experimental models. Another potential atrial-selective approach has recently been identified. Experimental studies have demonstrated important atrioventricular differences in the biophysical properties of the sodium channel and have identified sodium channel blockers that can exploit electrophysiological distinctions between atria and ventricles. Atrial-selective/predominant sodium channel blockers such as ranolazine effectively suppress AF in experimental models involving canine-isolated right atrial preparations at concentrations that produce little to no effect on electrophysiological parameters in ventricular myocardium. Chronic administration of amiodarone was also found to exert atrial-selective depression of INa-dependent parameters and thus to prevent the induction of AF. Ranolazine and amiodarone have in common the ability to rapidly dissociate from the sodium channel and to prolong the atrial action potential duration via inhibition of IKr. Our observations suggest that atrial-selective sodium channel block may be a fruitful strategy for the management of AF." @default.
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• W2149106024 date "2009-11-01" @default.
• W2149106024 modified "2023-09-25" @default.
• W2149106024 title "Atrial-selective sodium channel block as a novel strategy for the management of atrial fibrillation" @default.
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• W2149106024 doi "https://doi.org/10.1016/j.jelectrocard.2009.07.007" @default.
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