老龄化易发生左心房心律失常的电生理特征及其机制  

Electrophysiological properties and mechanism of aging for the susceptibility of left atrium to arrhythmogenesis in rabbits

作　　者：杨淑红[1] 杨峥[1] 吴成云[1] 李文星[1] 徐辉文[2] 

机构地区：[1]武汉大学人民医院外科门诊,武汉市430060 [2]武汉大学人民医院老年科,武汉市430060

出　　处：《中华医学杂志》2015年第28期2302-2306,共5页National Medical Journal of China

基　　金：湖北省自然科学基金（2011CDB504）;湖北省卫生厅科研基金（JX6B67）

摘　　要：目的 探讨老龄化兔易发生左心房心律失常的电生理特征及其机制.方法 按年龄取青龄（6个月龄）和老龄（26个月龄）健康雄性新西兰大耳白兔各25只,使用异丙肾上腺素（ISO）前后作对照,共分为青龄对照组、青龄药物组和老龄对照组、老龄药物组.常规微电极记录左心房组织的跨膜动作电位（tAP）,观察静息膜电位（RMP）、动作电位幅度（APA）、最大上升速率（Vmax）、复极化到20％和50％以及90％时程（APD20、APD50、APD90）、程控和短阵快速刺激下分别测定的有效不应期（AERP）及其房性心律失常.酶解法分离单个左心房细胞,膜片钳和激光扫描共聚焦显微镜技术分别观察L-型钙电流（ICa-L）和Ca2＋荧光强度在使用ISO前后变化.结果 老龄对照组左心房各APD及AERP均显著高于青龄对照组,APA、Vmax、RMP、AERP/APD90均显著低于青龄对照组（均P＜0.05）;在ISO作用后,青龄和老龄药物组左心房动作电位传导增快,但老龄药物组左心房动作电位形状改变和各APD值缩短更加明显,APA、Vmax、RMP幅度都显著增大（均P＜0.05）,动作电位之后出现更严重的延迟后除极及触发电活动;在电压钳制方式下,老龄对照组左心房细胞ICa-L均显著低于青龄对照组,当钳制电压为10 mV时,老龄对照组ICa-L电流密度显著低于青龄对照组[（6.3±0.8）比（9.5±1.3） pA/pF,P＜0.01],其电流-电压（Ⅰ-Ⅴ）曲线明显上抬.老龄药物组ICa-L电流密度显著高于青龄药物组[（15.9±3.1）比（11.3 ±2.6）pA/pF,P＜0.01],其ICa-L的Ⅰ-Ⅴ曲线处于其他各组最下部.老龄对照组左心房细胞内Ca2荧光强度显著低于青龄对照组[（437.9±21.7）比（778.3±19.5）μmol/L,P＜0.01];ISO干预后,老龄和青龄药物组左心房细胞内Ca2荧光强度均增强,但老龄药物组[Ca2＋];显著强于青龄药物组[（1635.6±51.6）比（1 008.7±34.5）μmol/L,P＜0.05].结论 老龄化左心房在ISO作�Objective To explore the electrophysiological properties and mechanism of aging for the susceptibility of left atrium （LA） to arrhythmogenesis in rabbits.Methods A total of 50 male New Zealand rabbits were divided into young （6 months,n =25） and aged （26 months,n =25） groups.According to comparisons before and after isoproterenol （ISO） dosing,young rabbits were further divided into young control and medication groups while aged ones into aged control and medication groups.Electrophysiological study was performed on perfused isolated left atrium and conventional microelectrodes were used for recording transmenbrane action potentials （tAP）,resting membrane potential （RMP）,amplitude of APs （APA）,maximum upstroke velocity （Vmax）,APs duration at 20％,at 50％ or at 90％ repolarization （APD20,APD50,APD90）,atrial effective refractory periods （AERP） and atrial arrhythmia inducibility before and after ISO dosing.L-type calcium current （ICa-L） was measured via whole-cell patch clamp technique.And fluorescent intensity of intracellular Ca2＋ was detected with Flup-3/AM loading by laser scanning confocal microscope in enzymatically dissociated single LA myocytes before and after dosing.Results Compared with major parameters of tAP in young control group,APDs and AERP significantly increased and APA,V RMP and AERP/APD90 obviously decreased in aged control group （all P ＜ 0.05）.Otherwise,the conduction of tAP was rapid and delayed afterdepolarizations （DADs） were induced in both young and aged medication groups after ISO dosing.However,as compared with major parameters of young medication group,APDs dramatically declined while APA,V RMP and DAD amplitude significantly increased.And triggered activity was induced in aged medication group （all P ＜ 0.05）.With voltage clamp model,ICa-L significantly declined in aged control group versus young control group.The peak current density of ICa-L dramatically decreased （（6.3 ±0.8） pA/pF in aged control group vs （9.5 �

关 键 词：左心房功能 心律失常 老龄化 电生理学技术 心脏 

分 类 号：R541.7[医药卫生—心血管疾病]