Effects of zatebradine and propranolol on canine ischemia and reperfusion-induced arrhythmias

European Journal of Pharmacology
H NaitoK Hashimoto

Abstract

1,3,4,5-Tetrahydro-7,8-dimethoxy-3[3-[[2-(3, 4-dimethoxyphenyl)-ethyl]methylamino]propyl]-2H-3-benzazepin-2-one -hy drochloride (Zatebradine) is a specific bradycardiac agent, blocking the hyperpolarization-activated pacemaker current (I(f)), and thus has no negative inotropic effect. The purpose of this study was to examine whether zatebradine is effective against ischemia and reperfusion-induced arrhythmias in dogs compared to propranolol. Arrhythmia was induced by ligation of the left anterior descending coronary artery followed by reperfusion. Ischemia-induced biphasic arrhythmias were suppressed in both zatebradine and propranolol groups. During ischemia, fatal ventricular fibrillation occurred in four dogs in the control group, 0 in the zatebradine group, and two dogs in the propranolol group. Of the 31 dogs subjected to reperfusion, mortality rates in the zatebradine, propranolol, and control groups were 56%, 75%, and 86%, respectively, and there were no significant differences. In the heart beating 10 beats/min faster than the predrug heart rate by atrial pacing, both zatebradine and propranolol attenuated ischemia-induced arrhythmias but did not affect reperfusion arrhythmias. Our results suggest that I(f) and/or beta-...Continue Reading

References

Jan 1, 1989·The American Journal of Physiology·M BernierD J Hearse
May 1, 1987·Journal of Molecular and Cellular Cardiology·W A CoetzeeC A Muller
Oct 1, 1984·British Journal of Pharmacology·M J CurtisM J Walker
Jan 1, 1993·Circulation Research·H YuI S Cohen
Feb 1, 1996·Japanese Journal of Pharmacology·Y X XueK Hashimoto

Citations

Feb 25, 2003·Life Sciences·Robert L HamlinCynthia A Carnes
Sep 6, 2005·Hypertension Research : Official Journal of the Japanese Society of Hypertension·Hiroshi NagaiHisayoshi Fujiwara
May 10, 2002·Journal of Cardiovascular Pharmacology and Therapeutics·Luyi SenBramah N Singh
Jan 24, 2006·Nature Medicine·Sharlene M DayJoseph M Metzger
Apr 18, 2017·Experimental and Therapeutic Medicine·Jie HouYan Zhu

Related Concepts

Zatebradine hydrochloride
Adrenergic beta-Antagonists
Metazoa
Cardiac Arrhythmia
Benzazepines
Diastolic Blood Pressure
Cardiac Pacing, Artificial
Cardiotonic Agents
Canis familiaris
Dose-Response Relationship, Drug

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