Comparison of electropharmacological effects of bepridil and sotalol in halothane-anesthetized dogs.
BACKGROUND
Bepridil is known to have a multiple ion channel-blocking property in the heart, which has been applied for the treatment of atrial fibrillation and drug-refractory ventricular tachyarrhythmias. In this study, the electro-pharmacological effects of bepridil were compared with those of dl-sotalol, a representative class III antiarrhythmic drug, using the halothane-anesthetized canine model.


RESULTS
Cardiovascular and electrophysiological variables were measured under the halothane anesthesia. Intravenous administration of bepridil (0.3 mg/kg, n=4) delayed the intraventricular conduction and prolonged the ventricular effective refractory period, whereas dl-sotalol (0.3 mg/kg, iv, n=4) inhibited atrioventricular conduction and prolonged the atrial and ventricular effective refractory period. The additional administration of 10 times the higher dose of bepridil or dl-sotalol (ie, 3 mg/kg, iv, n=4 for each group) decreased blood pressure, suppressed ventricular contraction and sinus automaticity, and prolonged the atrial and ventricular effective refractory period and monophasic action potential duration, in addition to the effects of the low dose.


CONCLUSIONS
The electropharmacological effects of bepridil and dl-sotalol were similar, although their potency for each cardiovascular variable varied significantly. These findings can be useful when selecting these drugs according to the pathophysiological condition of a patient.
Ishizaka
Tomomichi
T
Department of Pharmacology, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Chuo, Japan.
Takahara
Akira
A
Iwasaki
Hiroshi
H
Mitsumori
Yoshitaka
Y
Kise
Hiroaki
H
Nakamura
Yuji
Y
Sugiyama
Atsushi
A
D000319:Adrenergic beta-Antagonists / Q000097:blood / Q000494:pharmacology*; D018685:Anesthetics, Inhalation; D000818:Animals; D001283:Atrioventricular Node / Q000187:drug effects; D015764:Bepridil / Q000097:blood / Q000494:pharmacology*; D002036:Bundle of His / Q000187:drug effects; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography / Q000187:drug effects; D005260:Female; D006221:Halothane; D006329:Heart Conduction System / Q000187:drug effects*; D008297:Male; D023421:Models, Animal; D009200:Myocardial Contraction / Q000187:drug effects; D010138:Pacemaker, Artificial; D012849:Sinoatrial Node / Q000187:drug effects; D013015:Sotalol / Q000097:blood / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000097:blood / Q000494:pharmacology*
D000319:Adrenergic beta-Antagonists; D018685:Anesthetics, Inhalation; D014665:Vasodilator Agents; D015764:Bepridil; D013015:Sotalol; D006221:Halothane