Schräder R, Brooks M, Echt D S
Division of Cardiology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232.
J Cardiovasc Pharmacol. 1992 Jun;19(6):839-50. doi: 10.1097/00005344-199206000-00001.
Antiarrhythmic drugs are often required in patients with implantable cardioverter-defibrillator devices. Prior evidence suggests that drugs modulate defibrillation energy requirements by altering ion channel activity. To evaluate the effects of calcium ion channel activity on internal defibrillation energy requirements, the calcium antagonist verapamil and Bay K 8644, a calcium channel activator, were investigated in 30 open-chest, pentobarbital-anesthetized dogs. Defibrillation energies were applied across two epicardial patch electrodes. The likelihood of successful defibrillation was determined at various shock energy levels, and the 50 and 90% effective energy doses were calculated using nonlinear regression. In saline control experiments (n = 10), the stability of the preparation throughout the 6-h duration of the experiments could be demonstrated. Verapamil administration (n = 10) infused to a mean plasma concentration of 69 ng/ml increased the 50 and 90% effective defibrillation energies by 41 and 43% (p less than 0.05), respectively, and to a mean plasma verapamil concentration of 170 ng/ml by 95 and 75% (p less than 0.01), respectively. The mean cycle length during ventricular fibrillation decreased with verapamil and was inversely related to the change in defibrillation energy requirement. Administration of Bay K 8644 (n = 10) produced a slight increase in the 50% effective defibrillation energy (25%; p less than 0.05) and 90% effective defibrillation energy (17%; n.s.). The electrophysiologic effects of verapamil were neither prevented nor reversed by Bay K 8644. In conclusion, intravenous verapamil administration caused an increase in defibrillation energy requirements, but the mechanism by which verapamil exerted this effect remains unclear. These experimental data suggest that verapamil should be used in patients with automatic implantable cardioverter-defibrillator devices only after individual testing.
植入式心脏复律除颤器患者通常需要使用抗心律失常药物。先前的证据表明，药物通过改变离子通道活性来调节除颤能量需求。为了评估钙离子通道活性对体内除颤能量需求的影响，在30只开胸、戊巴比妥麻醉的犬中研究了钙拮抗剂维拉帕米和钙通道激活剂Bay K 8644。通过两个心外膜贴片电极施加除颤能量。在不同的电击能量水平下确定成功除颤的可能性，并使用非线性回归计算50%和90%有效能量剂量。在生理盐水对照实验（n = 10）中，可以证明整个6小时实验过程中制剂的稳定性。静脉输注维拉帕米（n = 10）使平均血浆浓度达到69 ng/ml时，50%和90%有效除颤能量分别增加了41%和43%（p < 0.05），使平均血浆维拉帕米浓度达到170 ng/ml时，分别增加了95%和75%（p < 0.01）。维拉帕米使室颤期间的平均心动周期长度缩短，且与除颤能量需求的变化呈负相关。静脉注射Bay K 8644（n = 10）使50%有效除颤能量略有增加（25%；p < 0.05），90%有效除颤能量增加了17%（无统计学意义）。Bay K 8644既不能预防也不能逆转维拉帕米的电生理效应。总之，静脉注射维拉帕米会导致除颤能量需求增加，但维拉帕米产生这种作用的机制尚不清楚。这些实验数据表明，维拉帕米仅应在个体测试后用于植入式自动心脏复律除颤器患者。
