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摘要
Na channel blockers are often used to treat atrial fibrillation (AF), but may sometimes cause ventricular contractile dysfunction. However, amiodarone, a multi-channel blocker with Na channel block, causes less contractile dysfunction. In this study, we tested the hypothesis that Na channel block by amiodarone is selective in atrial myocytes (AM) compared with ventricular myocytes (VM). %26lt;br%26gt;Na currents (I-Na) were measured using whole-cell patch-clamp technique in isolated rabbit AM and VM. Amiodarone inhibited I-Na in AM (IC50: 1.8 1.1 M; n 8) much more than in VM (40.4 11.9 M; n 7, P 0.01). Amiodarone at 10 M shifted the steady-state inactivation relationship in AM (16.2 1.7 mV shift, n 12) compared with VM (5.9 0.7 mV shift; n 13; P 0.01). For mexiletine, the inhibition of I-Na and inactivation curve shifts were comparable for AM and VM. The effects of amiodarone and mexiletine on conduction velocity (CV) in Langendorff-perfused rabbit hearts were evaluated using an optical mapping system. The decrease of CV by 3 M amiodarone was significantly larger in the atrium (18.9 3.8 change; n 5) compared with the ventricle (3.7 3.7; n 5; P 0.01). In contrast, mexiletine reduced CV equally in the atrium and the ventricle. %26lt;br%26gt;Amiodarone preferentially inhibits I-Na of AM compared with VM. Atrial selective Na channel block by amiodarone may contribute to treating AF with less effect on ventricular contractility than other Na channel blockers.
- 出版日期2013-4-1
