多非利特与Chromanol 293B对豚鼠心室乳头肌动作电位的影响  

Effects of Dofetide combined Chromanol 293B on the action potential of papillary muscle in guinea pigs

作　　者：李妙龄[1] 杜俊蓉[2] 周文[1] 魏燕[1] 杨艳[1] 刘智飞[1] 裴杰[1] 曾晓荣[1] 

机构地区：[1]泸州医学院心肌电生理学研究室,四川泸州646000 [2]四川大学药学院,四川成都610041

出　　处：《华西药学杂志》2011年第1期36-38,共3页West China Journal of Pharmaceutical Sciences

基　　金：四川省中医药管理局资助项目(200641)

摘　　要：目的研究多非利特和Chromanol 293B对豚鼠乳头肌动作电位的作用,探讨快速延迟整流钾通道(Ikr)和慢速延迟整流钾通道(Iks)电流抗心律失常的作用机制。方法用标准玻璃微电极技术记录豚鼠乳头肌的动作电位,观察不同刺激频率下动作电位各参数的变化。结果多非利特能浓度依赖性地延长动作电位的时程,随着刺激频率的增加,APD90延长的百分比明显减小,表明了其明显的负性频率依赖性;Chromanol 293B能剂量依赖性地延长动作电位的时间(APD),但作用较弱。在不同刺激频率下,10μmol.L-1 Chromanol 293B延长APD不具有频率依赖性;但能延长APD90,当加入0.1μmol.L-1多非利特后,可显著延长APD90,增强了在低频率时的作用,表现为负性频率依赖性。结论多非利特是作用于Ikr的纯Ⅲ类抗心律失常药物,具有明显的剂量和频率依赖性;Chromanol 293B是选择性作用于Iks的Ⅲ类抗心律失常药物,非频率依赖性的适度延长APD。两者联合应用明显增强了延长APD的作用,在慢心率时作用最强。OBJECTIVE To investigate the effect of specificity Ikr-blocking drug Dofetilide and selective Iks-blocking drug Chromanol 293B on the action potential of papillary muscle in guinea pigs and analyse the effective mechanism.METHODS The conventional glass microelectrode technique was used to record the action potential of papillary muscle in guinea pigs.The action potential profile was recorded under different stimulation frequency.RESULTS Dofetilide lengthened action potential duration APD（APD50,APD90） in a dose-dependent manner.Under different stimulation frequency,Dofetilide increased slowly stimulation rates in papillary muscle of guinea pig,which showed a significant reversed rate-dependent effect.Chromanol 293B lengthened action potential duration APD（APD50,APD90） in a dose-dependent manner.When treated with 0.1 μmol·L-1dofetilide in the presence of 10 μmol·L-1 Chromanol 293B,it showed a significant prolonged APD in reversed rate-dependent effect.CONCLUSION The class Ⅲ drugs Dofetilide strongly inhibited Ikr and showed a significant prolonged APD in dose and rate-dependent effects.Chromanol 293B was the selective Iks blocking agent in independent of stimulation frequency.

关 键 词：多非利特 Chromanol 293B 豚鼠乳头肌 动作电位时程 负性频率依赖性 

分 类 号：R96[医药卫生—药理学]