Furukawa Y, Xue Y X, Chiba S, Hashimoto K
Department of Pharmacology, Yamanashi Medical University, Japan.
Eur J Pharmacol. 1996 Apr 11;300(3):203-10. doi: 10.1016/0014-2999(95)00880-2.
To determine whether a hyperpolarization-activated current (If) participates in ventricular tachyarrhythmias, we investigated the effects of zatebradine, an I(f) inhibitor, on the ventricular tachyarrhythmias induced by ouabain, two-stage coronary ligation and epinephrine infusion in the dog heart. We determined atrial rate, ectopic ventricular rate, total heart rate and arrhythmic ratio (the number of ectopic ventricular beats divided by total heart beats). Zatebradine (0.15, 0.5 and 1.5 mg/kg, i.v.) dose dependently decreased the arrhythmic ratio, ectopic ventricular rate and atrial rate of the ouabain-induced ventricular tachyarrhythmias in pentobarbital-anesthetized dogs. The inhibition by zatebradine of the ventricular arrhythmias needed larger doses than the inhibition of the atrial rate. Zatebradine weakly depressed the ectopic ventricular rate but not the arrhythmic ratio of the ventricular arrhythmias induced by two-stage coronary ligation 24 h after the ligation in conscious dogs. Although neither the ectopic ventricular rate nor the arrhythmic ratio of the epinephrine-induced ventricular arrhythmias was affected by zatebradine, after treatment with zatebradine, the arrhythmias elicited by epinephrine developed more slowly. Together with the previously reported spectra of the effects of the antiarrhythmic agents in three ventricular tachyarrhythmia models, our results suggest that zatebradine may improve automaticity-related ventricular tachyarrhythmias due to I(f) inhibition or to other undetermined mechanisms in the heart.
为了确定超极化激活电流（If）是否参与室性心律失常，我们研究了If抑制剂扎替雷定对哇巴因、两阶段冠状动脉结扎和肾上腺素输注诱发的犬心室心律失常的影响。我们测定了心房率、异位心室率、总心率和心律失常比率（异位心室搏动数除以总心搏数）。在戊巴比妥麻醉的犬中，扎替雷定（0.15、0.5和1.5mg/kg，静脉注射）剂量依赖性地降低了哇巴因诱发的室性心律失常的心律失常比率、异位心室率和心房率。扎替雷定对室性心律失常的抑制作用所需剂量大于对心房率的抑制作用。在清醒犬两阶段冠状动脉结扎24小时后，扎替雷定对结扎诱发的室性心律失常的异位心室率有微弱抑制作用，但对心律失常比率无影响。虽然扎替雷定对肾上腺素诱发的室性心律失常的异位心室率和心律失常比率均无影响，但用扎替雷定治疗后，肾上腺素诱发的心律失常发展较慢。结合先前报道的三种室性心律失常模型中抗心律失常药物的作用谱，我们的结果表明扎替雷定可能由于抑制If或心脏中其他未确定的机制而改善与自律性相关的室性心律失常。
