Chézalviel F, Weissenburger J, Guhennec C, Jagueux M, Davy J M, Vernhet L, Simandoux V, Poirier J M, Cheymol G
Laboratoire de Pharmacologie, Faculté de Médecine Saint Antoine, Paris, France.
J Cardiovasc Pharmacol. 1993 Feb;21(2):212-20.
Mexiletine was recently shown to antagonize the effects of sotalol on repolarization of canine Purkinje fibers. The significance of this interaction for the antiarrhythmic properties of these drugs remains unknown. The antiarrhythmic effects of sotalol and mexiletine alone and in combination on induced ventricular tachycardias (VTs) were assessed in 20 conscious dogs with chronic infarction. Electrophysiological measurements and programmed stimulation were performed before and after the infusion of sotalol (4 mg/kg) or mexiletine (4 mg/kg), and after infusion of the combination. The electrophysiological parameters didn't change after mexiletine. Sotalol alone and the combination both similarly prolonged the QT interval and VERP. Induction of VT by programmed stimulation was not prevented by mexiletine, but the cycle length of monomorphic VT was increased in 7 of 10 dogs. The induction of VT was prevented by sotalol (11/16 dogs), but VTs were not slowed significantly. Sotalol plus mexiletine prevented VT as did sotalol alone (11/16 dogs). The combination also increased the cycle length of VT in all eight dogs with monomorphic VT. Thus, the antagonism shown in vitro appears to have no consequences in this model. On the contrary, the sotalol-mexiletine combination showed some additive antiarrhythmic effects on induced VT in dogs.
美西律最近被证明可拮抗索他洛尔对犬浦肯野纤维复极化的作用。这种相互作用对这些药物抗心律失常特性的意义尚不清楚。在20只患有慢性梗死的清醒犬中评估了索他洛尔和美西律单独及联合应用对诱发室性心动过速（VT）的抗心律失常作用。在输注索他洛尔（4mg/kg）或美西律（4mg/kg）之前和之后，以及输注联合用药之后，进行了电生理测量和程控刺激。美西律输注后电生理参数未发生变化。单独使用索他洛尔和联合用药均同样延长了QT间期和心室有效不应期（VERP）。美西律未能防止程控刺激诱发VT，但10只犬中有7只的单形性VT周期长度增加。索他洛尔可防止VT的诱发（16只犬中有11只），但VT并未显著减慢。索他洛尔加美西律与单独使用索他洛尔一样可防止VT（16只犬中有11只）。联合用药还使所有8只患有单形性VT的犬的VT周期长度增加。因此，体外显示的拮抗作用在该模型中似乎没有影响。相反，索他洛尔 - 美西律联合用药对犬诱发的VT显示出一些相加的抗心律失常作用。
