Weld F M, Bigger J T, Swistel D, Bordiuk J, Lau Y H
J Pharmacol Exp Ther. 1979 Aug;210(2):222-8.
To clarify the electrophysiological mechanisms of the antiarrhythmic effects of mexiletine, we examined the actions of mexiletine (0.1--30 mg/l) on action potential characteristics (phase 0 amplitude, overshoot, maximum upstroke velocity, maximum diastolic and activation voltages, duration at 50% and 90% repolarization) of cardiac Purkinje fibers using standard microelectrode techniques. In fibers stimulated at constant rate, mexiletine decreased phase 0 amplitude and Vmax and shortened the action potential. Mexiletine shortened action potential duration at lower concentrations than those which altered phase 0 depolarization. The effect of mexiletine on normal automaticity in cardiac Purkinje fibers was studied in fibers made automatic either by hypokalemia or by isoproterenol. Mexiletine suppressed normal automaticity by shifting activation voltage, so that spontaneous phase 4 depolarization reached a stable resting voltage without triggering regenerative phase 0 depolarization. The effects of mexiletine on abnormal automaticity were studied in Purkinje fibers intoxicated by ouabain. Mexiletine decreased the amplitude of or abolished either early or delayed after depolarizations induced by ouabain.
为阐明美西律抗心律失常作用的电生理机制，我们采用标准微电极技术，研究了美西律（0.1 - 30毫克/升）对心脏浦肯野纤维动作电位特征（0期振幅、超射、最大上升速度、最大舒张期和激活电压、50%和90%复极化时程）的影响。在以恒定频率刺激的纤维中，美西律降低0期振幅和Vmax并缩短动作电位。美西律在改变0期去极化的浓度之前，就能缩短动作电位时程。我们在低钾血症或异丙肾上腺素诱导自动节律的纤维中，研究了美西律对心脏浦肯野纤维正常自律性的影响。美西律通过改变激活电压抑制正常自律性，使自发的4期去极化达到稳定的静息电压，而不触发再生性0期去极化。我们在哇巴因中毒的浦肯野纤维中，研究了美西律对异常自律性的影响。美西律降低哇巴因诱导的早期或延迟后去极化的振幅或使其消失。
