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.