阻断Ryanodine受体对兔心肌肥厚触发性室性心律失常发生的影响

Effect of Ryanodine receptor blockage on triggered ventricular arrhythmia in rabbits with left ventricular hypertrophy

目的:研究阻断Ryanodine受体对兔心肌肥厚触发性室性心律失常发生的影响。方法:选择日本长耳兔,通过缩窄腹主动脉建立心肌肥厚模型(LVH组),并设立假手术组(仅游离腹主动脉,不进行缩窄)作为对照。8周后应用超声心动图证实心肌肥厚形成,采用酶解法分离左室心肌细胞,应用全细胞膜片钳技术记录动作电位,观察在异丙肾上腺素(1μmol/L)灌流和快频率(5Hz)电刺激条件下,单个心肌细胞晚期后除极(DAD)和触发活动的发生率,以及预先分别灌流钙调蛋白激酶Ⅱ抑制剂KN-93(1μmol/L)和Ryanodine受体阻滞剂兰尼碱(10μmol/L)对肥厚心肌细胞DAD和触发活动发生率的影响。结果:假手术组、LVH组、KN-93组和兰尼碱组DAD的发生率分别为0、85%、35%和20%,触发活动的发生率分别为0、60%、20%和10%,KN-93组和兰尼碱组DAD和触发活动的发生率较LVH组显著降低(P<0.05)。结论:阻断Ryanodine受体能够有效抑制兔心肌肥厚触发性室性心律失常的发生,Ryanodine受体有望成为防治该类心律失常的新靶点。

Objective： 1 o investigate the ettect ot Ryanoalne receptor blockage on trlggerect ventricular arrnym mia in rabbits with left ventrieular hypertrophy （LVH）. Method：Japanese rabbits were established LVH models by the coaretation of the abdominal aorta, while those in the sham group did not undergo the coarctation. After 8 weeks, single left ventricular myocyte was isolated by enzymatic dissociation method and action potential （AP） was recorded using whole cell patch clamp technique. Perfused with Tyrode＇s solution containing isoprenaline （1 μmol/L）, the frequency of delayed afterdepolarization （DAD） and triggered activity was recorded under high- frequency stimulation stimulation （5 Hz）. And the effect of KN-93 and Ryanodine perfusion on the frequency of DAD and triggered activity was observed. Result：The frequency of DAD was 0 in sham group, 85% in LVH group, 35% in KN 93 group, and 20% in Ryanodine group. The frequencies of triggered activity were 0, 60%, 20%, and 10%, respectively. The frequencies of DAD and triggered activity in KN-93 and Ryanodine groups were much lower than those in LVH group （P%0.05）. Conclusion： Blockage of Ryanodine receptor is a new method of treat- ment which effectively reduce the occurrence of triggered ventricular arrhythmia in rabbits with LVH.