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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 effects of dofetilide and Chromanol 293B on the action potentials of guinea pig papillary muscles and to explore the mechanism of anti-arrhythmia of Ikr and Iks currents. Methods Standard glass microelectrode technique was used to record the action potentials of guinea pig papillary muscles. The changes of action potentials under different stimulation frequencies were observed. Results Dofetilide could prolong the time course of action potential in a concentration-dependent manner. With the increase of stimulation frequency, the percentage of prolongation of APD90 significantly decreased, indicating a significant negative frequency dependence. Chromanol 293B dose-dependently Prolonged action potential time (APD), but less effective. At different stimulation frequencies, 10μmol.L-1 Chromanol 293B prolonged the APD dose-dependently, but prolonged APD90. When 0.1μmol.L-1 dofetilide was added, APD90 was significantly prolonged and enhanced at low frequency When the role of negative frequency dependence. CONCLUSION Dofetilide is a pure class III antiarrhythmic agent that acts on Ikr in a dose- and frequency-dependent manner. Chromanol 293B is a class III antiarrhythmic drug that selectively acts on Iks, with modestly prolonged non-frequency-dependent APD. The combination of both significantly enhance the role of prolonged APD, the strongest role in the slow heart rate.