Role of late sodium channel current block in the management of atrial fibrillation.
Cardiovasc Drugs Ther
; 27(1): 79-89, 2013 Feb.
Article
em En
| MEDLINE
| ID: mdl-23108433
ABSTRACT
The anti-arrhythmic efficacy of the late sodium channel current (late I(Na)) inhibition has been convincingly demonstrated in the ventricles, particularly under conditions of prolonged ventricular repolarization. The value of late I(Na) block in the setting of atrial fibrillation (AF) remains poorly investigated. All sodium channel blockers inhibit both peak and late I(Na) and are generally more potent in inhibiting late vs. early I(Na). Selective late I(Na) block does not prolong the effective refractory period (ERP), a feature common to practically all anti-AF agents. Although the late I(Na) blocker ranolazine has been shown to be effective in suppression of AF, it is noteworthy that at concentrations at which it blocks late I(Na) in the ventricles, it also potently blocks peak I(Na) in the atria, thus causing rate-dependent prolongation of ERP due to development of post-repolarization refractoriness. Late I(Na) inhibition in atria is thought to suppress intracellular calcium (Ca(i))-mediated triggered activity, secondary to a reduction in intracellular sodium (Na(i)). However, agents that block late I(Na) (ranolazine, amiodarone, vernakalant, etc) are also potent atrial-selective peak I(Na) blockers, so that the reduction of Na(i) loading in atrial cells by these agents can be in large part due to the block of peak I(Na). The impact of late I(Na) 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 I(Na) block may contribute more to inhibition of Ca(i)-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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fibrilação Atrial
/
Canais de Sódio
/
Bloqueadores dos Canais de Sódio
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Antiarrítmicos
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article