IKs 复极储备下调对心肌肥厚豚鼠室性心律失常发生的影响

目的：观察心肌肥厚时快激活延迟整流钾电流(rapidly activated delayed rectifier potassium channel，IKr)和慢 激活延迟整流钾电流(slowly activated delayed rectifier potassium channel，IKs)的变化，并探讨IKr和IKs阻断剂对心肌肥厚豚 鼠室性心律失常发生的影响。方法：豚鼠分为假手术组和左心室肥厚(left ventricular hypertrophy，LVH)组，制备LVH 模型。采用全细胞膜片钳技术记录心室肌细胞IKr和IKs电流，观察IKr和IKs电流的变化；给予豚鼠分别静脉注射IKr阻断 剂多非利特(0.04 mg/kg)和IKs阻断剂chromanol 293B(0.1 mg/kg)，观察其对LVH豚鼠QTc及室性心律失常发生的影响。 结果：豚鼠胸主动脉缩窄6周后，与假手术组相比，室间隔厚度，左室后壁厚度，QTc间期和细胞电容显著增加 (P<0.05或P<0.01)；LVH心室肌细胞IKs明显减少+60 mV：(0.36±0.03) pA/pF vs (0.58±0.05) pA/pF，P<0.01]；LVH对IKr无 明显影响。IKr阻断剂可显著延长LVH豚鼠QTc间期(P<0.01)，并增加室性心律失常的发生。IKs阻断剂对LVH豚鼠QTc间 期及室性心律失常的发生无明显影响。结论：IKs复极储备下调是心肌肥厚诱发室性心律失常的重要机制之一。

Effect of down-regulation of IKs repolarization-reserve on ventricular arrhythmogenesis in a guinea pig model of cardiac hypertrophy

Objective: To observe the changes of rapidly activated delayed rectifi er potassium channel (IKr) and slowly activated delayed rectifier potassium channel (IKs) in cardiac hypertrophy and to evaluate the eff ects 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.