Takahara Akira, Sugiyama Atsushi, Satoh Yoshioki, Hashimoto Keitaro
Department of Pharmacology, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Tamaho-cho, Nakakoma-gun, Yamanashi 409-3898, Japan.
Eur J Pharmacol. 2003 Aug 22;476(1-2):115-22. doi: 10.1016/s0014-2999(03)02127-7.
Potential utility of mexiletine for the treatment of sparfloxacin-induced long QT syndrome was assessed using the in vivo halothane-anesthetized canine model. At 30 min after the administration of a supratherapeutic dose of sparfloxacin (30 mg/kg, i.v.), the mean blood pressure and heart rate decreased, whereas repolarization process and effective refractory period of the ventricular muscle were significantly prolonged. Additional administration of a clinically recommended dose of mexiletine (3 mg/kg, i.v.) at this time point increased the mean blood pressure, suppressed ventricular contraction, delayed atrioventricular as well as intraventricular conduction, and shortened repolarization process and effective refractory period. The extent of abbreviation of the repolarization was more prominent than that of the refractoriness, indicating that mexiletine could decrease the electrical vulnerability of the heart during sparfloxacin overdose. Thus, mexiletine may become a promising pharmacological strategy against the drug-induced long QT syndrome.
使用体内氟烷麻醉犬模型评估了美西律治疗司帕沙星诱导的长QT综合征的潜在效用。在给予超治疗剂量的司帕沙星（30mg/kg，静脉注射）30分钟后，平均血压和心率下降，而心室肌的复极过程和有效不应期显著延长。此时额外给予临床推荐剂量的美西律（3mg/kg，静脉注射）可提高平均血压，抑制心室收缩，延迟房室以及心室内传导，并缩短复极过程和有效不应期。复极缩短的程度比不应期缩短更显著，表明美西律可降低司帕沙星过量时心脏的电易损性。因此，美西律可能成为一种有前景的治疗药物诱导长QT综合征的药理学策略。
