兔LQT2模型心室肌复极化的性别差异

本研究旨在探讨长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模型左心事原已存在的电生理异质性和心事复极动力学的特征。实验分为3组,上下常组以标准台氏液灌流;LQT2模型组给予含100gmol／L dl-sotalol的台式液灌流;LQT2模型＋低钾组给了含3．0mmol／LKCl、100μmol／L 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、l000和2000ms的S1刺激,同步记录心事肌内膜侧、外膜侧细胞动作电位,并记录跨壁心电图：在BCL为500和1000ms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人（P〈0．01）。BCL为1000ms时,LQT2模型组雌兔7例中1例发生尖端扭转性窀性心动过速（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≯频率依赖性。存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。

Gender-related differences of ventricular repolarization in LQT2 rabbit model

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 mumol/L dl-sotalol Tyrode's solution (LQT2 model group), and 100 mumol/L dl-sotalol plus 3.0 mmol/L KCl Tyrode's solution (LQT2 model plus hypokalemia group), buffered with 95% O2 and 5% CO2 [(36.0+/-1) degrees C]. Double diastolic threshold currents were delivered with basic cycle length (BCL) 2 000, 1 000 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 1 000 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 1 000 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.