蝙蝠葛碱对多非利特诱发的早后除极的治疗作用

Therapeutic Effects of Dauricine on Early Afterdepolariztions Induced by Dofetilide

目的研究蝙蝠葛碱(Dau)对多非利特(dof)诱发的早后除极(EADs)的治疗作用和可能机制。方法用腹主动脉缩窄法制备家兔心肌肥厚模型;标准微电极技术记录家兔右心室乳头肌动作电位,观察1μmol.L-1dof对正常、肥厚、低钾及肥厚+低钾状态下家兔乳头肌动作电位的影响;诱发出EADs后,给予终浓度30μmol.L-1的Dau,观察Dau对以上不同病理状况下动作电位时程(APD)和EADs的影响。结果dof延长家兔乳头肌动作电位,与正常组比较,差异有显著性(P<0.05);低钾和心肌肥厚时家兔乳头肌动作电位较正常家兔明显延长;dof在低钾和心肌肥厚状态下,EADs的发生率分别与正常组、低钾和心肌肥厚组相比均有显著升高;发生EADs后给予Dau,可明显降低EADs的发生率。结论蝙蝠葛碱对EADs具有良好的治疗作用,机制可能与其对多个离子通道的作用有关。

Objective To investigate the effects and possible mechanisms of dauricine （Dau） on early afterdepolarizations induced by dofetilide, Methods Cardiac hypertrophy was induced in rabbits by aortic banding; using conventional microelectrode techniques, the effects of dofetilide at the concentration of 1 μmol · L^-1 on action potential duration （APD） and incidence of early afterdepolarizations （EADs） were studied and compared in rabbit papillary muscles between control and different pathological conditions, including hypokalemia and hypertrophy ; the effects of Dau in concentrations of 30 μmol · L^-1 on APD and EADs were observed after EADs were induced by the pathologic conditions mentioned above. Results Compared with control, dofetilide significantly prolonged the APD of rabbit papillary muscle; the same phenomena were also found in hypokalemia and hypertrophy; dofetilide significantly advanced the incidence of EADs in hypokalemia concomitant with hypertrophy ; Dau inhibited the prolongation of APD and significantly suppressed the incidence of EADs induced by dofetilide. Conclusion Dau exerts good therapeutic effects on early afterdepolarizations induced by dofetilide and these effects may be associated with inhibition of Dau on several ion channels.