Document Detail


Effects of zatebradine and propranolol on canine ischemia and reperfusion-induced arrhythmias.
MedLine Citation:
PMID:  10666509     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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-adrenoceptors rather than the bradycardiac action might be related to the antiarrhythmic effects during ischemia, but that they do not play a role in the generation of the reperfusion-induced ventricular arrhythmias.
Authors:
H Naito; Y Furukawa; D Chino; C Yamada; K Hashimoto
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  European journal of pharmacology     Volume:  388     ISSN:  0014-2999     ISO Abbreviation:  Eur. J. Pharmacol.     Publication Date:  2000 Jan 
Date Detail:
Created Date:  2000-03-16     Completed Date:  2000-03-16     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  1254354     Medline TA:  Eur J Pharmacol     Country:  NETHERLANDS    
Other Details:
Languages:  eng     Pagination:  171-6     Citation Subset:  IM    
Affiliation:
Department of Pharmacology, Yamanashi Medical University, Tamaho-cho, Nakakoma-gun, Yamanashi, 409-3898, Japan.
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MeSH Terms
Descriptor/Qualifier:
Adrenergic beta-Antagonists / therapeutic use*
Animals
Arrhythmias, Cardiac / drug therapy*,  etiology,  physiopathology
Benzazepines / therapeutic use*
Blood Pressure / drug effects
Cardiac Pacing, Artificial
Cardiotonic Agents / therapeutic use*
Dogs
Dose-Response Relationship, Drug
Electrophysiology
Female
Heart Rate / drug effects
Male
Myocardial Ischemia / complications*,  physiopathology
Myocardial Reperfusion Injury / complications*,  physiopathology
Propranolol / therapeutic use*
Chemical
Reg. No./Substance:
0/Adrenergic beta-Antagonists; 0/Benzazepines; 0/Cardiotonic Agents; 525-66-6/Propranolol; 85175-67-3/zatebradine

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