Arita M, Goto M, Nagamoto Y, Saikawa T
Br J Pharmacol. 1979 Sep;67(1):143-52.
1 The effects of mexiletine (Kö1173) were investigated in canine isolated cardiac Purkinje fibres and ventricular muscle with microelectrodes. Some Purkinje fibres were depolarized by mechanical stretch to induce spontaneous activity with slow upstroke velocity. The preparations were stimulated at rates of 1, 2, 3 and 4 Hz. The drug concentrations tested were 0.4, 2 and 10 mug/ml in Tyrode solution (KCl = 5.4 mM).2 The ;therapeutic' drug concentration (2 mug/ml) shortened action potential duration and effective refractory period of Purkinje fibres, the effect being pronounced at lower stimulation rates. In ventricular fibres, action potential duration changes were not consistent while the effective refractory period was prolonged.3 In depolarized Purkinje fibres showing automatic activity, the drug (0.4 or 2 mug/ml) depressed phase 4 depolarization and reduced the firing rate without changing maximum diastolic potential. However, when depolarized Purkinje fibres were electrically driven at a constant rate, the maximum diastolic potential became more negative with a concomitant decrease of pacemaker slope and increase of maximum rate of rise (V(max)) of action potentials.4 Moderate (2 mug/ml) to high (10 mug/ml) concentrations of the drug depressed V(max) in Purkinje fibres stimulated at 2 Hz by 12 and 42% respectively and depressed ;membrane responsiveness'. The decrease in V(max) depended upon the stimulation rate, being minimum at the lowest (1 Hz) and maximum at the highest (4 Hz) stimulation rate.5 The drug (2 mug/ml) improved V(max) of the earliest propagated premature action potentials by shifting the takeoff potential to more negative levels in both Purkinje and ventricular fibres.6 Membrane conductance in fibres mounted in a single sucrose gap chamber was increased by the drug (2 mug/ml) in both fibre types in normal and in Na(+)-deficient solutions. This increase was attributed to an increase in membrane K(+) permeability produced by the drug.7 All these effects are similar to those of lignocaine, diphenylhydantoin or aprindine, and can explain the antiarrhythmic action of mexiletine.
用微电极研究了美西律（Kö1173）对犬离体心脏浦肯野纤维和心室肌的作用。一些浦肯野纤维通过机械拉伸去极化以诱导自发活动，其上升支速度缓慢。以1、2、3和4Hz的频率刺激标本。在台氏液（KCl = 5.4mM）中测试的药物浓度为0.4、2和10μg/ml。
“治疗”药物浓度（2μg/ml）缩短了浦肯野纤维的动作电位时程和有效不应期，在较低刺激频率下该作用更为明显。在心室纤维中，动作电位时程变化不一致，而有效不应期延长。
在显示自动活动的去极化浦肯野纤维中，药物（0.4或2μg/ml）抑制4期去极化并降低发放频率，而不改变最大舒张电位。然而，当以恒定频率电驱动去极化浦肯野纤维时，最大舒张电位变得更负，同时起搏斜率降低，动作电位最大上升速率（V(max)）增加。
中等（2μg/ml）至高（10μg/ml）浓度的药物分别使以2Hz刺激的浦肯野纤维的V(max)降低12%和42%，并降低“膜反应性”。V(max)的降低取决于刺激频率，在最低（1Hz）刺激频率时最小，在最高（4Hz）刺激频率时最大。
药物（2μg/ml）通过将起始电位移至更负的水平，改善了浦肯野纤维和心室纤维中最早传播的早搏动作电位的V(max)。
在正常和缺钠溶液中，安装在单个蔗糖间隙室中的纤维的膜电导在两种纤维类型中均被药物（2μg/ml）增加。这种增加归因于药物引起的膜K(+)通透性增加。
所有这些作用均与利多卡因、苯妥英或茚满丙二胺的作用相似，并且可以解释美西律的抗心律失常作用。
