阻断Ryanodine受体对兔儿茶酚胺敏感性室速模型心律失常发生的抑制作用

Effect of ryanodine receptor blockage on incidence of cardiac arrhythmia in rabbit models with catecholaminergic polymorphic ventricular tachycardia

目的:观察阻断Ryanodine受体对兔儿茶酚胺敏感性室速(CPVT)模型心律失常发生的抑制作用。方法:将40只日本长耳兔随机分为4组:正常对照组、模型组、钙调蛋白激酶Ⅱ抑制剂KN-93组、Ryanodine受体阻滞剂兰尼碱组,每组10只。制备兔左室楔形心肌块的灌流模型,同步记录心内、外膜动作电位及跨壁心电图。正常组灌流台氏液,模型组灌流咖啡因和异丙肾上腺素建立CPVT模型,KN-93组和兰尼碱组预先给予各自药物预灌,然后灌流咖啡因和异丙肾上腺素,观察在快频率程序刺激下各组触发活动和室性心动过速的发生率。结果:对照组、模型组、KN-93(1μmol/L)和兰尼碱组(10μmol/L)触发活动的发生率分别为0/10、10/10、4/10和2/10,多形性室速或室颤的发生率分别为0/10、9/10、3/10、1/10;提示KN-93和兰尼碱均可减少CPVT模型的触发活动和室性心律失常的发生(均P<0.05)。结论:阻断Ryanodine受体能够有效抑制CPVT模型的触发性室性心律失常,Ryanodine受体有望成为防治该类心律失常新的重要靶点。

Objective ： To study the effect of ryanodine receptor blockage on incidence of cardiac arrhythmia in rabbit models with catecholaminergic polymorphic ventricular tachycardia （CPVT）. Methods ： Forty Japanese rabbits were randomized divided into four groups： control group, model group, Calmodufin Kinase II KN-93 group and ryanodine group （10 for each group）. Arterially peffused left ventricular wedge preparations were made, and transmembraue action potentials （APs） of epicardium and endocardium and transmural ECG were simultaneously recorded. The control group was peffused with Tyrode＇s solution, while the model group with isoprotereuol ＋ caffeine to mimic CPVT. The KN-93 group was pre-perfused with KN-93 and then with KN-93 ＋ isoproterenol ＋ caffeine. And the ryanodine group was pre-perfused with ryanodine and then with ryanodine ＋ isoproterenol ＋ caffeine. The frequency of triggered APs and ventricular tachycardia of each group was recorded under high-frequency stimulation. Results ： The frequency of triggered APs were 0/10 in the control group, 10/10 in the model group, 4/10 in the KN-93 group, and 2/10 in the ryanodine group. The frequencies of polymorphic ventricular tachycardia or ventricular fibrillation were 0/10,9/10,3/10, and 1/10 ,respectively. KN-93 and ryanodine may decrease the frequencies of triggered ventricular arrhythmias in models with CPVT （ P 〈 0.05 ）. Conclusion ： Blockage of ryanodine receptor can effectively reduce the occurrence of triggered ventricular arrhythmia in CPVT model and may be used as a new means of treatment.