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兔LQT2模型心室肌复极化的性别差异

刘丽平, 杨琳, 赵朝, 陈前

西安交通大学医学院第一附属医院心血管内科，环境与疾病相关基因教育部重点实验室心血管离子通道病研究室.陕西，西安 710061

摘要

该研究旨在探讨长QT综合征(long QT syndromes, LQTS)室性心律失常发生的性别差异及其电生理机制，初步观察了 不同性别兔LQT2模型左心室原已存在的电生理异质性和心室复极动力学的特征。实验分为3组，正常组以标准台氏液灌流； LQT2模型组给予含100 #mu#mol/L {sl dl}--sotalol的台式液灌流；LQT2模型+低钾组给予含3.0 mmol/L KCl、100 #mu#mol/L {sl dl}--sotalol的台式液灌流。采用冠状动脉旋支灌注兔左室心肌楔形组织块标本，应用浮置玻璃微电极记录技术进行记录。给予基础刺激周长 (basic cycle length, BCL)为500、1000和2000 ms的S1刺激，同步记录心室肌内膜侧、外膜侧细胞动作电位，并记录跨壁心 电图；在BCL为500和1000 ms时加用S2程序刺激以记录动作电位时程(action potential duration, APD)恢复曲线。研究发现： 在不同刺激频率时，3组实验雌兔心肌细胞的跨壁复极化离散(transmural dispersion of repolarization, TDR)、APD恢复曲线斜率均大于雄兔，有显著性差异(P<0.05)，并呈频率依赖性；LQT2模型组及LQT2模型+低钾组雌雄兔TDR、APD恢复曲线 斜率较正常组明显增大(P<0.01)。BCL为1000 ms时，LQT2模型组雌兔7例中1例发生尖端扭转性室性心动过速(torsade de pointes,TdP); LQT2模型+低钾组雌兔7例中5例诱发TdP，雄兔7例中2例诱发TdP，有显著性差异( P<0.05)。结果提示：LQT2模型心肌原已存在的电生理异质性和动态异质性均有明显的性别差异，并呈频率依赖性。在LQT2模型中，TDR以及 APD恢复曲线斜率的增大可能是雌性动物较雄性更易发生尖端扭转性心律失常的原因。

关键词： 长QT综合征; 性别; 动作电位; 尖端扭转型室性心动过速

Gender-related differences of ventricular repolarization in LQT2 rabbit model

Liu Liping, Yang Lin, Zhao Zhao, Chen Qian

Department of Cardiology, Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, the First Affiliated Hospital of Medical College, Xi'an Jiaotong University.Xian 710061,Shaanxi

Abstract

To explore the cellular mechanism responsible for the gender-related differences of ventricular tachyarrhythmias in long QT syndromes (LQTS), we observed the characteristics of pre-existing electrophysiological heterogeneity and dynamics of ventricular repolarization in different gender of LQT2 rabbit models. The intracellular floating microelectrodes technique was used to record transmembrane action potentials simultaneously from epicardial and endocardial sites of the arterially perfused rabbit left ventricular wedge preparation; in the mean time, the electrocardiogram (ECG) was also recorded. The wedge preparations were placed in a small tissue bath and arterially perfused with normal Tyrode's solution (control group), 100 #mu#mol/L dl-sotalol Tyrode's solution (LQT2 model group), and 100 μmol/L dl-sotalol plus 3.0 mmol/L KCl Tyrode's solution (LQT2 model plus hypokalemia group), buffered with 95% O_(2) and 5% CO_(2) [(36.0±0.1)℃]. Double diastolic threshold currents were delivered with basic cycle length (BCL) 2000, 1000 and 500 ms (S1), respectively, to record transmembrane action potentials and transmural ECG. Each driving train of S1 is with 20 beats. To determine action potential duration restitution (APDR) curves, the S1-S2 programmed stimuli were used. The tissue was paced at 1000 ms and 500 ms cycle length (S1) for eight beats, followed by a single premature stimulus (S2). The S1-S2 coupling interval was progressively shortened with 10 ms decrements until the S2 failed to capture. The results showed that female rabbits exhibited significantly longer transmural dispersion of repolarization (TDR) and steeper maximal slopes of APDR curves than that in male rabbits at same pacing rates (P<0.05), and which were pacing rate-dependent. In the condition of dl-sotalol plus hypokalemia, the TDR and the maximal slopes of APDR curves were significantly increased in comparison with that in the control group (P<0.01). At a BCL of 1000 ms of seven experiments, one female showed torsade de pointes (TdP) in the LQT2 model group; five females and two males showed TdP in LQT2 model plus hypokalemia group, showing significant gender-related differences (P<0.05). The present findings suggest that the pre-existing electrophysiological and dynamic heterogeneity in the LQT2 model shows an obvious gender-related difference and pacing rate-dependence. Both increased TDR and steepness of APDR in female rabbits are possibly the major factors which prompt the TdP generation in female LQT2 rabbits more easily than in male rabbits.

Key words: Long QT syndrome;Gender;Action potential;Torsade de pointes

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引用本文：

刘丽平, 杨琳, 赵朝, 陈前. 兔LQT2模型心室肌复极化的性别差异 [J]. 生理学报 2005; 57 (6): .

Liu Liping, Yang Lin, Zhao Zhao, Chen Qian . Gender-related differences of ventricular repolarization in LQT2 rabbit model . Acta Physiol Sin 2005; 57 (6): (in Chinese with English abstract).