Kaverina N V, Lyskovtsev V V, Popova E P
Laboratory of Circulation System Pharmacology, Institute of Pharmacology, Russian Academy of Medical Sciences, Baltiiskaya Str., 8, Moscow, 125315 Russia.
Eksp Klin Farmakol. 2003 Jan-Feb;66(1):27-33.
Electrophysiological mechanisms of the action of cardiocyclide, nibentan, and sotalol--antiarrhythmic agents of class III--was studied in dogs with experimental myocardial infarction induced by a two-step occlusion of the coronary artery. Cardiocyclide exhibited the properties typical of the class III antiarrhythmics by prolonging the ventricular repolarization and increasing the effective refractory periods in the atrium and ventricles. The degree of manifestation of these antiarrhythmic effects of cardiocyclide is independent of the induced heart rate, which is related to the ability of this drug to block the slow activation component (IKs) of the delayed rectified potassium current. Nibentan elongates the QT interval and increases the effective atrial and ventricular refractory periods, but the effect was dependent of the stimulation frequency. Sotalol, which also exhibited the properties of a class III antiarrhythmogen possessing beta-blocking activity, produced more pronounced inhibiting action upon the sinus node function and conduction (in comparison with the analogous effects of cardiocyclide). This is probably related to the ability of sotalol to block the cardiac adrenoreceptors. The effect of sotalol is also frequency-dependent, which is related to the blocking of rapid activating component (IKr) of) of the delayed rectified potassium current. On the background of isoproterenol infusion, cardiocyclide completely retained the electrophysiological and antiarrhythmic effects. The efficacy of nibentan and sotalol with respect to the repolarization and refractoriness significantly decrease under the conditions of sympathetic nervous system activation. The ability of sotalol to suppress the sinus node function and conduction on the background of isoproterenol infusion is retained.
研究了Ⅲ类抗心律失常药物环心环素、尼苯坦和索他洛尔在冠状动脉两步闭塞诱导的实验性心肌梗死犬中的电生理作用机制。环心环素通过延长心室复极化并增加心房和心室的有效不应期，表现出Ⅲ类抗心律失常药物的典型特性。环心环素这些抗心律失常作用的表现程度与诱导的心率无关，这与该药物阻断延迟整流钾电流的缓慢激活成分（IKs）的能力有关。尼苯坦延长QT间期并增加心房和心室的有效不应期，但该作用取决于刺激频率。索他洛尔也表现出具有β受体阻断活性的Ⅲ类抗心律失常药物的特性，对窦房结功能和传导产生更明显的抑制作用（与环心环素的类似作用相比）。这可能与索他洛尔阻断心脏肾上腺素能受体的能力有关。索他洛尔的作用也具有频率依赖性，这与阻断延迟整流钾电流的快速激活成分（IKr）有关。在输注异丙肾上腺素的背景下，环心环素完全保留了电生理和抗心律失常作用。在交感神经系统激活的情况下，尼苯坦和索他洛尔对复极化和不应期的疗效显著降低。在输注异丙肾上腺素的背景下，索他洛尔抑制窦房结功能和传导的能力得以保留。
