Ishizaka Tomomichi, Takahara Akira, Iwasaki Hiroshi, Mitsumori Yoshitaka, Kise Hiroaki, Nakamura Yuji, Sugiyama Atsushi
Department of Pharmacology, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Chuo, Japan.
Circ J. 2008 Jun;72(6):1003-11. doi: 10.1253/circj.72.1003.
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.
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.
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.
已知苄普地尔在心脏具有多种离子通道阻滞特性，已被用于治疗心房颤动和药物难治性室性快速性心律失常。在本研究中，使用氟烷麻醉的犬模型，比较了苄普地尔与Ⅲ类抗心律失常代表性药物dl-索他洛尔的电药理学作用。
在氟烷麻醉下测量心血管和电生理变量。静脉注射苄普地尔（0.3mg/kg，n = 4）延迟室内传导并延长心室有效不应期，而dl-索他洛尔（0.3mg/kg，静脉注射，n = 4）抑制房室传导并延长心房和心室有效不应期。额外给予10倍高剂量的苄普地尔或dl-索他洛尔（即3mg/kg，静脉注射，每组n = 4），除了低剂量的作用外，还降低血压、抑制心室收缩和窦性自律性，并延长心房和心室有效不应期及单相动作电位持续时间。
苄普地尔和dl-索他洛尔的电药理学作用相似，尽管它们对每个心血管变量的效能有显著差异。根据患者的病理生理状况选择这些药物时，这些发现可能有用。
