Wang Hegui, Huang Ting, Wang Zheng, Ge Nannan, Ke Yongsheng
Department of Cardiology, Yijishan Hospital of Wannan Medical College, Wuhu Anhui 241001, China
Department of Cardiology, Yijishan Hospital of Wannan Medical College, Wuhu Anhui 241001, China.
Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2018 Apr 28;43(4):428-433. doi: 10.11817/j.issn.1672-7347.2018.04.015.
To observe the changes of rapidly activated delayed rectifier potassium channel (IKr) and slowly activated delayed rectifier potassium channel (IKs) in cardiac hypertrophy and to evaluate the effects of IKr and IKs blocker on the incidence of ventricular arrhythmias in guinea pigs with left ventricular hypertrophy (LVH). Methods: Guinea pigs were divided into a sham operation group and a left ventricular hypertrophy (LVH) group. LVH model was prepared. Whole cell patch-clamp technique was used to record IKr and IKs tail currents in a guinea pig model with LVH. The changes of QTc and the incidence rate of ventricular arrhythmias in LVH guinea pigs were observed by using the IKr and IKs blockers. Results: Compared with cardiac cells in the control group, the interventricular septal thickness at end systole (IVSs), left ventricular posterior wall thickness at end systole (LVPWs), QTc interval and cell capacitance in guinea pigs with LVH were significantly increased (P<0.05); while IKs densities were significantly reduced [+60 mV: (0.36±0.03) pA/pF vs (0.58±0.05) pA/pF, P<0.01]. However, LVH exerted no significant effect on IKr densities. IKr blocker markedly prolonged the QTc interval (P<0.01) and increased the incidence of ventricular arrhythmias in guinea pigs with LVH compared with the control guinea pigs. In contrast, IKs blocker produced modest increase in QTc interval in guinea pigs of control group with no increase in LVH animals. IKs blocker did not induce ventricular arrhythmias incidence in either control or LVH animals. Conclusion: The cardiac hypertrophy-induced arrhythmogenesis is due to the down-regulation of IKs.
观察心脏肥大时快速激活延迟整流钾通道（IKr）和缓慢激活延迟整流钾通道（IKs）的变化，并评估IKr和IKs阻滞剂对左心室肥厚（LVH）豚鼠室性心律失常发生率的影响。方法：将豚鼠分为假手术组和左心室肥厚（LVH）组，制备LVH模型。采用全细胞膜片钳技术记录LVH豚鼠模型中的IKr和IKs尾电流。使用IKr和IKs阻滞剂观察LVH豚鼠QTc的变化和室性心律失常的发生率。结果：与对照组心肌细胞相比，LVH豚鼠的收缩末期室间隔厚度（IVSs）、收缩末期左心室后壁厚度（LVPWs）、QTc间期和细胞电容显著增加（P<0.05）；而IKs密度显著降低[+60 mV：（0.36±0.03）pA/pF对（0.58±0.05）pA/pF，P<0.01]。然而，LVH对IKr密度无显著影响。与对照豚鼠相比，IKr阻滞剂显著延长LVH豚鼠的QTc间期（P<0.01）并增加室性心律失常的发生率。相比之下，IKs阻滞剂使对照组豚鼠QTc间期适度增加，而LVH动物无增加。IKs阻滞剂在对照组或LVH动物中均未诱导室性心律失常的发生率。结论：心脏肥大诱导的心律失常是由于IKs下调所致。
