地高辛改变老龄兔心房电重构而易于诱发心房颤动的作用及其机制  

Effects and mechanism of digoxin on atrium electrical remodeling and susceptibility of atrial fibrillation in aged rabbits

作　　者：王腾[1] 王清秀 吴平亚 陈玉婷[1] 杨淑红[1] 黄燕[1] 刘韬[1] Wang Teng;Wang Qingxiu;Wu Pingya;Chen Yuting;Yang Shuhong;Huang Yan;Liu Tao(Department of Cardiology, Renmin Hospital of Wuhan University & Cardiovascular Research Institute of Wuhan University, Wuhan 430060, China;Medical Career Technical College of Wuhan University, Wuhan 430060, China;Hongshan District Zhangjiawan Street Community Health Service Centre, Wuhan 430070, China)

机构地区：[1]武汉大学人民医院心内科武汉大学心血管病研究所, 430060 [2]武汉大学医学职业技术学院,430060 [3]武汉市洪山区张家湾街社区卫生服务中心,430070

出　　处：《中华心血管病杂志》2019年第8期608-613,共6页Chinese Journal of Cardiology

基　　金：湖北省自然科学基金(2016CKB709);湖北省卫计委科研基金(WJ2015MB088).

摘　　要：目的探讨地高辛改变老龄家兔的心房电重构而易于诱发心房颤动(房颤)的作用及其机制。方法将老龄雄性新西兰大耳白兔20只分为两组,即老龄组及老龄+地高辛干预形成的地高辛组,每组10只。记录心电图,测量兔心率、RR间期、QT间期、ST段及P波离散度。麻醉开胸暴露心脏,记录在体心房肌单相动作电位最大上升速率(Maxdv/dt),平台期电位,复极化恢复到10%、20%、90%时程(APD10、APD20、APD90),基础刺激周长(BCL)为200 ms心房有效不应期(AERP200)、离散度(dERP200)及其BCL为300和150 ms的频率自适应性(fERP);短阵快速刺激下诱发房颤的BCL和诱发率。处死动物取出心脏,酶解法分离单个心房肌细胞,全细胞膜片钳技术和激光扫描共聚焦显微镜加Fluo-3/AM荧光染色技术观察各组心房肌细胞L-型钙电流(ICa-L)及其电流-电压(I-V)曲线和心房肌细胞内Ca2+荧光强度变化。结果与老龄组比较,地高辛组心率更快,RR和QT间期更短,ST段抬高及P波离散度增大更明显(P均<0.05),动作电位的Maxdv/dt和平台期电位增加、APD10和APD20延长、APD90缩短均更明显(P均<0.01);地高辛组fERP(0.81±0.15比0.67±0.05)和房颤诱发率(6/8比4/9)较高(P均<0.01)。在电压钳制方式下,地高辛明显增加老龄兔心房肌细胞ICa-L,当指令电位10 mV时,地高辛组兔心房肌细胞ICa-L的电流密度明显大于老龄组[(15.45±2.38)pA/pF比(7.03±1.69)pA/pF,P<0.01],其I-V曲线明显下移。地高辛组兔心房肌细胞内Ca2+荧光强度增强,细胞内Ca2+浓度增高[(1 748±173)μmol/L比(478±88)μmol/L,P<0.01]。结论地高辛使老龄兔心房在原有电重构的基础上再一次发生了异常电重构,加重了老龄兔心房的易感性而使房颤易于发生,其机制可能是地高辛异常增加了老龄心房肌细胞ICa-L和细胞内Ca2+浓度,引起钙超载和钙振荡所致。Objective To investigate the effects and mechanism of digoxin on atrium electrical remodeling and susceptibility of atrial fibrillation (AF) in aged rabbits. Methods Twenty aged male New Zealand rabbits were divided into aged group and aged plus digoxin group (n=10 each). Electrical parameters including heart rate (HR), RR and QT interval, ST segment and P wave dispersion from normal Ⅱ electrocardiogram, and the maximum upstroke velocity (Maxdv/dt), plateau potential (plateau P), action potential duration of 10%, 20% and 90%(APD10, APD20, APD90) from recording of monophasic action potential (MAP), as well as atrial effective refractory period (AERP200) and dispersion (dERP200) with 200 ms of basic cycle length (BCL), and frequency self adaptation of AERP with 300 ms and 150 ms of BCLs (fERP) were recorded and compared between the 2 groups. BCLs and inducibility of AF post programmed electrical stimulation and Burst-pacing in left atrium tissue of rabbits in vivo were also analyzed. The L-type calcium current (ICa-L) in 2 groups were recorded via whole-cell patch clamp technique, and the fluorescence intensity of intracellular free Ca2+ was detected with Flup-3/AM loading by the laser scanning confocal microscope in enzymatically dissociated single rabbit atrial myocytes. Results Compared with aged group, the heart rate was faster, RR and QT interval were obvious shorter, ST segment was raised and P wave dispersion was significantly increased in aged plus digoxin group (all P<0.05). Moreover, compared with aged group, the Maxdv/dt and plateau P were obviously increased, APD10 and APD20 were significantly prolongated, and APD90 was significantly shorter in aged plus digoxin group (all P<0.01). Otherwise, the fERP was markedly increased (0.81±0.15 vs. 0.67±0.05), and the induced rate of AF was obviously higher in aged plus digoxin group than in aged group (6/8 vs. 4/9)(all P<0.01). With voltage clamp model, digoxin significantly increased ICa-L of atrial myocytes of aged rabbits, When command potential was 10 mV

关 键 词：心房颤动 地高辛 心房电重构 钙通道 

分 类 号：R541.75[医药卫生—心血管疾病]