Steinberg M I, Wiest S A
J Cardiovasc Pharmacol. 1984 Jul-Aug;6(4):614-21. doi: 10.1097/00005344-198407000-00010.
The intracellular electrophysiological properties of a new, orally effective antiarrhythmic agent, indecainide hydrochloride, were studied in isolated canine myocardial preparations stimulated at 1 Hz and superfused with Tyrode's solution. In Purkinje fibers, indecainide (10(-6) and 3 X 10(-6) M) decreased the maximal rate of rise of phase 0 (Vmax), conduction velocity, action potential duration APD, and effective refractory period, and shifted the membrane response curve by 5 mV in a hyperpolarizing direction. In papillary muscle, APD was unchanged, but Vmax was decreased. The effect of the drug on Vmax was rate dependent, but over physiologically relevant cycle lengths (370 to 1,000 ms), Vmax remained relatively constant. In the presence of indecainide (3 X 10(-6) M) and at a basic cycle length of 333 ms, the rate constant for block onset was 0.06 and 0.1 action potentials-1 in Purkinje fiber and papillary muscle, respectively. The recovery of Vmax from maximum steady-state block was half completed in Purkinje fibers and muscle in 52 and 49 s, respectively. No resting block was apparent in either tissue at normal resting membrane potential. Indecainide had only minimal effects on automaticity arising from normal or depolarized (barium) membrane potentials. Thus, indecainide is a potent class I local anesthetic antiarrhythmic agent that depresses Vmax and conduction in cardiac tissues. The depressant effects of indecainide are completely dependent on prior activation of the tissue, but because of its slow kinetics for recovery from sodium channel block, little additional change in Vmax occurs within physiologically relevant heart rates and prematurity intervals.
在以1Hz频率刺激并灌注台氏液的离体犬心肌标本中，研究了一种新型口服有效的抗心律失常药物盐酸茚卡尼的细胞内电生理特性。在浦肯野纤维中，茚卡尼（10^(-6)和3×10^(-6)M）降低了0期最大上升速率（Vmax）、传导速度、动作电位时程（APD）和有效不应期，并使膜反应曲线向超极化方向偏移5mV。在乳头肌中，APD未改变，但Vmax降低。药物对Vmax的影响呈频率依赖性，但在生理相关的心动周期长度（370至1000ms）内，Vmax保持相对恒定。在存在茚卡尼（3×10^(-6)M）且基础心动周期长度为333ms时，浦肯野纤维和乳头肌中阻滞起始的速率常数分别为0.06和0.1次动作电位^(-1)。浦肯野纤维和肌肉中Vmax从最大稳态阻滞恢复的半衰期分别为52秒和49秒。在正常静息膜电位下，两种组织中均未出现静息阻滞。茚卡尼对正常或去极化（钡）膜电位引起的自律性影响极小。因此茚卡尼是一种强效的I类局部麻醉抗心律失常药物，可抑制心脏组织中的Vmax和传导。茚卡尼的抑制作用完全依赖于组织的先前激活，但由于其从钠通道阻滞恢复的动力学缓慢，在生理相关的心率和早搏间期内，Vmax几乎没有额外变化。
