Nesterenko V V, Aniukhovskiĭ E P, Starmer Ch F, Beloshapko G G, Ivanovich T, Bugriĭ E M, Mazaev A V, Rozenshtraukh L V
Kardiologiia. 1990 Mar;30(3):81-7.
Experiments with recording the time of intraventricular reentry of the canine heart by a special protocol of stimulation showed that the first-line antiarrhythmic agents having various kinetics, ethacizine and lidocaine, compete for their binding to the Na+ channels of cardiac fibers. As a result of this competition, additivity was not found in the effects of ethacizine, 1.5 mg/kg, and lidocaine, 12 mg/kg, on the rate of intraventricular conduction at heart rate under 180/min. At higher cardiac rhythm values, the total effects of the two agents on the conduction were observed. The experimental evidence confirm the results of mathematical modelling of the combined effects of ethacizine and lidocaine on the intraventricular conduction velocity, which were calculated on the basis of kinetic constants for binding and dissociation of the agents to Na+ channels. The findings show that when the two first-line antiarrhythmics having a substantially different kinetics were used in combination, their antiarrhythmic effect may be enhanced without their total effects on the rate of normal intraventricular conduction velocity reentry.
通过一种特殊的刺激方案记录犬心室内折返时间的实验表明,具有不同动力学的一线抗心律失常药物乙胺碘呋酮和利多卡因,会竞争与心肌纤维钠通道的结合。由于这种竞争,在心率低于180次/分钟时,1.5毫克/千克的乙胺碘呋酮和12毫克/千克的利多卡因对室内传导速率的影响未发现相加性。在更高的心律值时,观察到这两种药物对传导的总效应。实验证据证实了基于乙胺碘呋酮和利多卡因与钠通道结合和解离的动力学常数计算得出的它们对室内传导速度联合效应的数学建模结果。研究结果表明,当联合使用两种动力学有显著差异的一线抗心律失常药物时,它们的抗心律失常作用可能增强,而对正常室内传导速度折返速率的总效应不变。