PMCC PMCC

Search tips
Search criteria

Advanced
Results 1-2 (2)
 

Clipboard (0)
None
Journals
Authors
Year of Publication
Document Types
1.  Atrial-selective sodium channel block as a novel strategy for the management of atrial fibrillation 
Safe and effective pharmacologic management of atrial fibrillation (AF) is one of the greatest challenges facing an aging society. Currently available pharmacologic strategies for rhythm control of AF are associated with ventricular arrhythmias and in some cases multi-organ toxicity. Consequently, drug development has focused on atrial-selective agents such as IKur blockers. Recent studies suggest that IKur block alone may be ineffective for suppression of AF and may promote AF in healthy hearts. Recent experimental studies have demonstrated other important electrophysiologic differences between atrial and ventricular cells, particularly with respect to sodium channel function, and have identified sodium channel blockers that exploit these electrophysiologic distinctions. Atrial-selective sodium channel blockers, such as ranolazine and amiodarone, effectively suppress and/or prevent the induction of AF in experimental models, while producing little to no effect on ventricular myocardium. These findings suggest that atrial-selective sodium channel block may be a fruitful new strategy for the management of AF.
doi:10.1111/j.1749-6632.2009.05086.x
PMCID: PMC2866199  PMID: 20201889
antiarrhythmic drugs; arrhythmias; pharmacology; electrophysiology
2.  Atrial-Selective Sodium Channel Block as a Strategy for Suppression of Atrial Fibrillation 
Antiarrhythmic drug therapy remains the principal approach for suppression of atrial fibrillation (AF) and flutter (AFl) and prevention of their recurrence. Among the current strategies for suppression of AF/AFl is the development of antiarrhythmic agents that preferentially affect atrial, rather than ventricular electrical parameters. Inhibition of the ultrarapid delayed rectifier potassium current (IKur), present in the atria, but not in the ventricles, is an example of an atrial-selective approach. Our recent study examined the hypothesis that sodium channel characteristics differ between atrial and ventricular cells and that atrial-selective sodium channel block is another effective strategy for the management of AF. We have demonstrated very significant differences in the inactivation characteristics of atrial versus ventricular sodium channels and a striking atrial selectivity for the action of ranolazine, an inactivated-state sodium channel blocker, to produce use-dependent block of the sodium channels, leading to depression of excitability, development of post-repolarization refractoriness (PRR), and suppression of AF. Lidocaine and chronic amiodarone, both predominantly inactivated-state sodium channel blockers, also produced a preferential depression of sodium channel–dependent parameters (VMax conduction velocity, diastolic threshold of excitation, and PRR) in the atria. Propafenone, a predominantly open-state sodium channel blocker, produced similar changes of electrophysiological parameters, which were was not atrial-selective. The ability of ranolazine, chronic amiodarone, and propafenone to prolong the atrial action potential potentiated their ability to suppress AF in coronary-perfused canine atrial preparations. In conclusion: Our data demonstrate important differences in the inactivation characteristics of atrial versus ventricular sodium channels and a striking atrial selectivity for the action of agents like ranolazine to produce use-dependent block of sodium channels leading to suppression of AF. Our findings suggest that atrial-selective sodium channel block may be a valuable strategy to combat AF.
doi:10.1196/annals.1420.012
PMCID: PMC2366169  PMID: 18375582
electrophysiology; cardiac arrhythmias; lidocaine; amiodarone; ranolazine; propafenone

Results 1-2 (2)