[临床医学]于波-心房选择性钠通道阻滞剂在房颤中的应用20111120.ppt

心房选择性钠通道阻滞剂在房颤治疗中的应用 中国医科大学第一医院 于 波 心肌细胞的动作电位和离子通道 钠通道的特性 晚钠电流（late Ina， INaL ） 延长心房的ERP而不影响心室，选择性作用于心房肌的通道，对于心室肌通道无影响 对心房肌组织重构具有有益作用 无明显器官毒副作用，与其它心脏药物无配伍禁忌和不良影响 良好药代动力学特性，起效快，半衰期长 不影响或能够提高患者的远期生存率 Ranolazine blunts sotalol-induced action potential prolongation in dogs Vernakalant’s Frequency-Dependent Block of Na Currents Targets AF Effects of Vernakalant on Atrial Tissue from Humans with Atrial Fibrillation Vernakalant Prolongs Atrial Refractory Period: Human EP Study Effects of Vernakalant on Atrial Tissue from Humans with AF Phase II trial： CRAFT (Dose Ranging Study) Clinical Efficacy and Safety 静脉注射维纳卡兰与胺碘酮转复新近发生房颤AVRO研究 Background— Currently available antiarrhythmic drugs are only moderately effective against atrial fibrillation (AF) and may cause ventricular proarrhythmia. AVE0118 is a blocker of atrium-specific early K+ currents (IKur/Ito). Methods and Results— Effects of intravenous AVE0118 and dofetilide on atrial effective refractory period (AERP) and inducibility of AF were measured before and after 48-hours of AF-induced electrical remodeling in the goat. During persistent AF (53±19 days), the cardioversion efficacy and effects on atrial wavelength of AVE0118, dofetilide, and ibutilide were evaluated. QT durations were measured during atrial pacing and persistent AF. After 48 hours of AF, the effect of dofetilide on AERP was reduced, and induction of AF was not prevented. In contrast, the class III action of AVE0118 was enhanced, and AF inducibility decreased from 100% to 32% (P0.001). At 1, 3, and 10 mg · kg–1 · h–1, AVE0118 terminated persistent AF in 1 of 8, 3 of 8, and 5 of 8 goats, respectively. Dofetilide and ibutilide terminated AF in 1 of 5 and 2 of 7 goats. AVE0118 0.5, 1.5, and 5 mg/kg prolonged the AERP during AF and increased the fibrillation wavelength from 6.7±0.6 to 8.5±0.5, 9.7±0.5, and 11.2±0.9 cm (P0.01). Whereas dofetilide and ibutilide prolonged QT duration, AVE0118 had no appreciable effect. Conclusions— AVE0118 markedly pr