Evaluation of antiarrhythmic drugs on defibrillation energy requirements in dogs. Sodium channel block and action potential prolongation.
Evaluation of antiarrhythmic drugs on defibrillation energy requirements in dogs. Sodium channel block and action potential prolongation.
复制标题
抗心律失常药物对犬除颤能量需求的评估。
DOI：
10.1161/01.cir.79.5.1106
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发表时间：
1989
期刊：
影响因子：
37.8
通讯作者：
Cato,E
中科院分区：
文献类型：
--
作者：
Echt,DS;Black,JN;Barbey,JT;Coxe,DR;Cato,E
据报道，抗心律失常药物对除颤能量需求产生不同的影响。然而，这些药物的体外电生理效应与除颤能量需求变化之间的关系还没有得到系统的研究。因此，我们评价了钠通道阻滞剂利多卡因和普鲁卡因胺，动作电位延长药N-乙酰普鲁卡因胺和氯硝铵，钾电流阻滞剂铯在急性犬模型中的作用，这些药物与人类用于室颤测试的内弹簧和心外膜膜片电极相同。在78只狗身上进行了10个系列的实验。用非线性回归方法得出能量剂量与除颤成功率的关系曲线，以及每个实验条件下50%和90%的有效能量剂量。盐水对照实验表明，该制剂在实验的6小时内是稳定的。利多卡因使除颤能量需求量增加一倍(P<0.001)，平均血药浓度为8.20微克/毫升。利多卡因对除颤能量的影响是可逆的，存在于治疗性血药浓度，与血药浓度呈线性相关(r=0.69，P<0.002)，甚至在仅发生5秒的室颤后也存在。相反，普鲁卡因胺在平均血浆浓度为8.5和13微克/毫升时对除颤能量没有影响，即使在长时间(30秒)的室颤发作后也是如此，而N-乙酰普鲁卡因胺、氯菲铵和铯都将除颤所需的能量减少了13-27%。此外，随着N-乙酰普鲁卡因胺的加入，有减弱利多卡因引起的除颤能量需求增加的趋势。所有药物均延长了平均室颤周期长度。利多卡因缩短QT间期，而其他药物均使QT延长(p<0.05)。利多卡因的主要电生理作用是阻断钠通道，而N-乙酰普鲁卡因胺、氯普鲁卡因胺和铯主要延长动作电位时程，而普鲁卡因胺则同时发挥这两种作用。因此，这些数据表明，钠通道阻断和动作电位延长对除颤能量需求具有显著的拮抗调制作用。
Antiarrhythmic drugs have been reported to produce variable effects on defibrillation energy requirements. However, the relation between the in vitro electrophysiologic effects of these agents and the changes in defibrillation energy requirements have not been systematically examined. Therefore, we evaluated the effects of the sodium channel blocking drugs lidocaine and procainamide, the action potential prolonging drugs N-acetyl procainamide and clofilium, and the potassium current blocker cesium in acute canine models with the same internal spring and epicardial patch electrodes used in humans for ventricular defibrillation testing. Ten series of experiments were performed in 78 dogs. Nonlinear regression was used to derive curves of energy dose versus percent successful defibrillation attempts and the 50% and 90% effective energy dose for each experimental condition. Saline control experiments indicated that the preparation was stable throughout the 6-hour duration of the experiments. Lidocaine doubled the defibrillation energy requirement (p less than 0.001) at a mean plasma concentration of 8.2 micrograms/ml. The effect of lidocaine on defibrillation energy was reversible, present at therapeutic plasma concentrations, linearly related to plasma concentration (r = 0.69, p less than 0.002), and present even after only 5-second episodes of ventricular fibrillation. In contrast, procainamide had no effect on defibrillation energy at mean plasma concentrations of 8.5 and 13 micrograms/ml, even after prolonged (30-second) episodes of ventricular fibrillation, whereas N-acetyl procainamide, clofilium, and cesium all decreased the energy requirement for defibrillation by 13-27%. Moreover, with the addition of N-acetyl procainamide, there was a trend toward diminishing the increase in defibrillation energy requirement caused by lidocaine. All agents prolonged the mean ventricular fibrillation cycle length. Lidocaine shortened the QT interval, whereas all other agents increased the QT (p less than 0.05). The major electrophysiologic effect of lidocaine is of sodium channel blockade, whereas, N-acetyl procainamide, clofilium, and cesium predominantly increase the action potential duration, and procainamide exerts both effects. Thus, these data indicate that sodium channel block and action potential prolongation exert significant and antagonistic modulating effects on defibrillation energy requirements.