Effects of zatebradine on ouabain-, two-stage coronary ligation- and epinephrine-induced ventricular tachyarrhythmias

• Published in: European journal of pharmacology 1996-04, Vol.300 (3), p.203-210
• Main Authors: Furukawa, Yasuyuki, Xue, Yi-xue, Chiba, Shigetoshi, Hashimoto, Keitaro
• Format: Article
• Language: English
• Subjects: Animals; Antiarythmic agents; Automaticity; Benzazepines - blood; Benzazepines - pharmacology; Biological and medical sciences; Cardiac dysrhythmias; Cardiology. Vascular system; Cardiotonic Agents - blood; Cardiotonic Agents - pharmacology; Cardiovascular system; Dogs; Dose-Response Relationship, Drug; Epinephrine; Female; Heart; Heart Rate - drug effects; Heart, dog; Hyperpolarization-activated current ( If); Ligation; Male; Medical sciences; Ouabain; Pharmacology. Drug treatments; Tachycardia, Ventricular - etiology; Tachycardia, Ventricular - prevention & control; Vasoconstrictor Agents; Ventricular arrhythmia; Zatebradine
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/0014-2999(95)00880-2

To determine whether a hyperpolarization-activated current ( I f) 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.