晚钠电流抑制剂对心房间传导的影响及其抗心房颤动作用的机制探讨

Effects of the late sodium current inhibitor on the interatrial conduction time and acetylcholine-induced atrial fibrillation

目的 观察不同钠通道抑制剂对心房间及心室内传导时间的浓度依赖性和频率依赖性影响和对乙酰胆碱诱发心房颤动（房颤）的治疗作用,探讨晚钠电流抑制剂抗房颤的可能机制.方法 19只新西兰兔离体心脏采用改良K-H缓冲液灌流,在不同的起搏频率下（3.3Hz、5.0Hz和6.6Hz）,给予不同浓度的雷诺嗪、普罗帕酮和TTX （tetrodotoxin）,分别记录相应的心房间及心室内传导时间;并采用乙酰胆碱诱发的房颤模型,观察雷诺嗪对房颤负荷的影响.结果 雷诺嗪（1～15 μmol/L,n=6）在不同刺激频率下均显著延长心房间传导时间,呈浓度和频率依赖性;在心室,雷诺嗪只有在高浓度（≥15 μmol/L）时才显著延长心室内传导时间;TTX和普罗帕酮相似,在不同刺激频率下,当浓度增加到1 μnol/L以上时,显著延长心房间及心室内传导时间.雷诺嗪使心房间传导时间的延长显著大于对心室内传导时间的影响（n=7,P＜0.01）,而TTX（n=7）和普罗帕酮（n=6）延长心房内传导时间及心室内传导时间的程度相类似（P＞0.05）.雷诺嗪（10～30 μmol/L）降低心房最大可激动频率并降低乙酰胆碱诱发房颤的负荷（n=5和4,P＜0.05）.结论 晚钠电流抑制剂雷诺嗪与传统钠通道抑制剂（TTX及普罗帕酮）相比有显著的心房选择性,可延长心房间传导时间,降低心房最大可激动频率,抑制乙酰胆碱诱发的房颤.

Objective To observe the frequency-and concentration-dependent effects of late sodium current inhibitor on the interatrial and intraventricular conduction time and acetylcholine-induced atrial fibrillation （AF）.Methods New-Zealand White rabbit hearts were isolated and perfused in Langendorff mode.Hearts were paced at right atrium and para-His bundle area,and electrical signals were recorded from the left atrium and the apex to measure the interatrial and intraventricular conduction time.Results Ranolazine （1-15 μmol/L） prolonged interatrial conduction time in frequency-and concentration-dependent manners.Ranolazine prolonged the intraventricular conduction time at high concentration （〉15 μmol/L） but not at low and therapeutic concentrations （1-10 μmol/L）.Ranolazine also exerted the ability of reducing AF burden and terminating AF induced by acetylcholine.In contrast,TTX（tetrodotoxin） and propafenone （1-3 μmol/L） prolonged both interatrial and intraventricular conduction time.Conclusion Ranolazine is relatively atrial selective to prolong interatrial conduction time in frequency-and concentration-dependent manners and can suppresses acetylcholine-induced AF.