Chen Xiaowei, Qin Mu, Jiang Weifeng, Zhang Yu, Liu Xu
Department of Cardiology, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China.
PLoS One. 2017 Sep 1;12(9):e0183671. doi: 10.1371/journal.pone.0183671. eCollection 2017.
To explore the cardiac electrophysiological characteristics of cardiac hypertrophy and its influence on the occurrence of ventricular tachyarrhythmias.
Adult C57BL6 mice were randomly divided into a surgery group and a control group. Thoracic aortic constriction was performed on mice in the surgery group, and cardiac anatomical and ultrasonic evaluations were performed to confirm the success of the cardiac hypertrophy model 4 weeks after the operation. Using the Langendorff method of isolated heart perfusion, monophasic action potentials (MAPs) and the effective refractory period (ERP) at different parts of the heart (including the epi- and endo-myocardium of the left and right ventricles) were measured, and the induction rate of ventricular tachyarrhythmias was observed under programmed electrical stimulus (PES) and burst stimulus. Whole-cell patch-clamp was used to obtain the I-V characteristics of voltage-gated potassium channels in cardiomyocytes of different parts of the heart (including the epi- and endo-myocardium of the left and right ventricles) as well as the channels' properties of steady-state inactivation and recovery from inactivation.
The ratio of heart weight to body weight and the ratio of left ventricular weight to body weight in the surgery group were significantly higher than those in the control group (P < 0.05). Ultrasonic evaluation revealed that both interventricular septal diameter (IVSD) and left ventricle posterior wall diameter (LVPWD) in the surgery group were significantly larger than those in the control group (P < 0.05). Under PES and burst stimuli, the induction rates of arrhythmias in the surgery group significantly increased, reaching 41.2% and 23.5%, respectively. Both the QT interval and action potential duration (APD) in the surgery group were significantly longer than in the control group (P<0.01), and the changes showed obvious spatial heterogeneity. Whole-cell patch-clamp recordings demonstrated that the surgery group had significantly lower potassium current densities (IPeak, Ito, IKur, Iss, and IK1) at different parts of the heart than the control group (P < 0.01), and there were significant differences in the half-inactivation voltage (V1/2) and the inactivation-recovery time constant (τ) of Ito and IKur at different parts of the heart (P < 0.01) between the surgery group and the control group. In addition, the surgery group had significantly lower densities of IPeak, Ito, and IKur in cells of the endo-myocardium (P < 0.05), and the changes showed obvious spatial heterogeneity.
Changes in the current density and function of potassium channels contributed to irregular repolarization in cardiac hypertrophy, and the spatially heterogeneous changes of the channels may increase the occurrence of ventricular arrhythmias that accompany cardiac hypertrophy.
探讨心肌肥厚的心脏电生理特征及其对室性快速性心律失常发生的影响。
将成年C57BL6小鼠随机分为手术组和对照组。对手术组小鼠进行胸主动脉缩窄，并在术后4周进行心脏解剖和超声评估以确认心肌肥厚模型构建成功。采用Langendorff离体心脏灌注法，测量心脏不同部位（包括左、右心室的心外膜和心内膜）的单相动作电位（MAPs）和有效不应期（ERP），并在程序电刺激（PES）和猝发刺激下观察室性快速性心律失常的诱发率。采用全细胞膜片钳技术获取心脏不同部位（包括左、右心室的心外膜和心内膜）心肌细胞电压门控钾通道的I-V特性以及通道的稳态失活和失活后恢复特性。
手术组的心脏重量与体重之比以及左心室重量与体重之比均显著高于对照组（P<0.05）。超声评估显示，手术组的室间隔直径（IVSD）和左心室后壁直径（LVPWD）均显著大于对照组（P<0.05）。在PES和猝发刺激下，手术组的心律失常诱发率显著增加，分别达到41.2%和23.5%。手术组的QT间期和动作电位时程（APD）均显著长于对照组（P<0.01），且变化呈现明显的空间异质性。全细胞膜片钳记录显示，手术组心脏不同部位的钾电流密度（IPeak、Ito、IKur、Iss和IK1）均显著低于对照组（P<0.01），手术组与对照组在心脏不同部位Ito和IKur的半失活电压（V1/2）和失活后恢复时间常数（τ）方面存在显著差异（P<0.01）。此外，手术组心内膜细胞中的IPeak、Ito和IKur密度显著降低（P<0.05），且变化呈现明显的空间异质性。
钾通道电流密度和功能的改变导致心肌肥厚时复极不规则，通道的空间异质性改变可能增加心肌肥厚伴发的室性心律失常的发生。
