Kidwell G A, Gonzalez M D
Jefferson Medical College, Thomas Jefferson University Department of Medicine, Philadelphia, Pennsylvania.
J Cardiovasc Pharmacol. 1993 Apr;21(4):621-32. doi: 10.1097/00005344-199304000-00017.
Programmed electrical stimulation (PES) was used to compare the effects of flecainide and D-sotalol in a canine occlusion-reperfusion infarction model. The increase in the effective refractory period (ERP) was greater with D-sotalol than with flecainide (26.4 +/- 5.2 vs. 10.3 +/- 2.7 ms). In contrast, ventricular activation time was significantly increased by flecainide (from 72 +/- 2 to 87 +/- 3 ms) but was unchanged after D-sotalol administration (from 73 +/- 2 to 75 +/- 2 ms). Thirteen dogs with inducible sustained ventricular arrhythmias at control became noninducible after drug administration. All but one of these favorable drug responses were associated with D-sotalol. In contrast, 10 noninducible dogs at control had sustained ventricular arrhythmias induced after drug administration. All of these adverse responses were associated with flecainide (p < 0.0001). An increase in the ratio of conduction to refractoriness was observed in 100% of adverse drug trials but in only 25% of favorable drug trials (p = 0.003). These data suggest that flecainide enhances induction of sustained ventricular arrhythmias in this postinfarction canine model. This proarrhythmic drug effect may be related to the selective effect of flecainide on myocardial conduction.
在犬类闭塞再灌注梗死模型中，采用程控电刺激（PES）比较氟卡尼和D - 索他洛尔的效果。D - 索他洛尔使有效不应期（ERP）的增加幅度大于氟卡尼（26.4±5.2对10.3±2.7毫秒）。相比之下，氟卡尼显著增加心室激活时间（从72±2毫秒增至87±3毫秒），而给予D - 索他洛尔后心室激活时间无变化（从73±2毫秒至75±2毫秒）。13只在对照时可诱发持续性室性心律失常的犬在给药后变得不可诱发。除一只犬外，所有这些良好的药物反应均与D - 索他洛尔有关。相比之下，10只在对照时不可诱发的犬在给药后诱发了持续性室性心律失常。所有这些不良反应均与氟卡尼有关（p < 0.0001）。在100%的不良药物试验中观察到传导与不应期比值增加，但在仅25%的良好药物试验中观察到该比值增加（p = 0.003）。这些数据表明，在该梗死后期犬模型中，氟卡尼增强了持续性室性心律失常的诱发。这种促心律失常药物效应可能与氟卡尼对心肌传导的选择性作用有关。
