Rouet R, Ducouret P
Cellular and Molecular Physiology Laboratory, Caen University, France.
J Cardiovasc Pharmacol. 1994 Aug;24(2):177-83.
In clinical studies, flecainide, a class IC antiarrhythmic drug, exhibited antiarrhythmic properties against supraventricular arrhythmias but also showed proarrhythmic effects in ventricular arrhythmias. We studied the effects of flecainide on action potential (AP) maximum rate of increase (Vmax) in guinea-pig right ventricular muscle. The effects of flecainide were studied at 3 concentrations (10(-5), 5 x 10(-6), 10(-6) M) and five frequencies (0.5, 1, 1.5, 2, and 3 Hz). At these three concentrations, flecainide caused little and not significant tonic block. In contrast, flecainide caused a frequency-and dose-dependent reduction in Vmax (at 3 Hz, the time constant of Vmax decrease was 3.6 +/- 0.2 s for 10(-5) M, 3.8 +/- 0.2 s for 5 x 10(-6) M, and 7.1 +/- 1.3 s for 10(-6) M). At 3 Hz, the time constants measured as number of APs were 11 +/- 2 for flecainide 10(-5) M, 12 +/- 2 for 5 x 10(-6) M, and 22 +/- 2 for 10(-6) M, respectively. At 10(-6) M, spontaneous arrhythmias occurred at all frequencies studied. Assuming that changes in Vmax reflect changes in Na+ fast current amplitude, our results suggest that flecainide is an open Na channel blocker showing frequency- and dose-dependent effects in the range of 0.5-3 Hz.
在临床研究中，Ic类抗心律失常药物氟卡尼对室上性心律失常具有抗心律失常特性，但对室性心律失常也显示出促心律失常作用。我们研究了氟卡尼对豚鼠右心室肌动作电位（AP）最大上升速率（Vmax）的影响。在3种浓度（10⁻⁵、5×10⁻⁶、10⁻⁶M）和5种频率（0.5、1、1.5、2和3Hz）下研究了氟卡尼的作用。在这三种浓度下，氟卡尼引起的强直阻滞轻微且无统计学意义。相比之下，氟卡尼导致Vmax呈频率和剂量依赖性降低（在3Hz时，10⁻⁵M时Vmax降低的时间常数为3.6±0.2秒，5×10⁻⁶M时为3.8±0.2秒，10⁻⁶M时为7.1±1.3秒）。在3Hz时，以动作电位数量测量的时间常数，氟卡尼10⁻⁵M时为11±2，5×10⁻⁶M时为12±2，10⁻⁶M时为22±2。在10⁻⁶M时，在所研究的所有频率下均出现自发性心律失常。假设Vmax的变化反映了钠快速电流幅度的变化，我们的结果表明氟卡尼是一种开放钠通道阻滞剂，在0.5 - 3Hz范围内显示出频率和剂量依赖性效应。
