Atrium-Selective Sodium Channel Block as a Strategy for Suppression of Atrial Fibrillation

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Abstract
Background— The development of selective atrial antiarrhythmic agents is a current strategy for suppression of atrial fibrillation (AF). Methods and Results— Whole-cell patch clamp techniques were used to evaluate inactivation of peak sodium channel current (INa) in myocytes isolated from canine atria and ventricles. The electrophysiological effects of therapeutic concentrations of ranolazine (1 to 10 μmol/L) and lidocaine (2.1 to 21 μmol/L) were evaluated in canine isolated coronary-perfused atrial and ventricular preparations. Half-inactivation voltage of INa was ≈15 mV more negative in atrial versus ventricular cells under control conditions; this difference increased after exposure to ranolazine. Ranolazine produced a marked use-dependent depression of sodium channel parameters, including the maximum rate of rise of the action potential upstroke, conduction velocity, and diastolic threshold of excitation, and induced postrepolarization refractoriness in atria but not in ventricles. Lidocaine also pref...

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