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目的:制备LQT_3模型(一种QT延长综合症),研究美西律对LQT_3模型的作用。方法:用ATX Ⅱ制备LQT_3模型,在钠通道、动作电位和心电图三个水平观察美西律对豚鼠LQT_3模型的作用。结果:用ATX Ⅱ作用后,心肌细胞的钠通道长期开放模式的发生频率和开放时间常数显著性增加:动作电位APD_(50)和APD_(90)分别延长25.8％、26.1％;0期最大除极速度增加12％:QT间期和QTc分别增加12.8％和16.9％。在ATX Ⅱ存在的同时加入美西律(0.7 mmol/L),钠通道的开放几率明显降低。ATX Ⅱ(40 nmol/L)使动作电位时程延长后,美西律(1,5,15,45,70 μmol/L)使APD_(50)分别缩短0.5％,6.7％,14.4％,19.4％,18.8％,同时也使APD_(90),V_(max)呈相应的减小。在整体动物心电图记录中,美西律呈剂量依赖性缩短由ATX Ⅱ引起的QT和QTc延长效应。结论:美西律可以用来治疗LQT_3。
OBJECTIVE: To prepare LQT_3 model (a QT prolongation syndrome) to study the effect of mexiletine on LQT_3 model. Methods: The LQT_3 model was prepared by ATX Ⅱ. The effects of mexiletine on LQT_3 model in guinea pigs were observed at three levels of sodium channel, action potential and electrocardiogram. Results: After ATX Ⅱ treatment, the frequency and open time constant of long-term sodium channel of cardiomyocytes were significantly increased: the action potentials APD_ (50) and APD_ (90) were extended by 25.8% and 26.1% Pole speed increased by 12%: QT interval and QTc increased by 12.8% and 16.9% respectively. In the presence of ATX Ⅱ while adding mexiletine (0.7 mmol / L), sodium channel opening was significantly reduced. After ATX Ⅱ (40 nmol / L) prolonged the action potential duration, the APD_ (50) was reduced by 0.5%, 6.7%, 14.4% and 19.4 % And 18.8%, respectively. At the same time, APD_ (90) and V_ (max) decrease correspondingly. In the whole animal electrocardiogram recording, mexiletine dose-dependently shortened the QT and QTc prolongation effects caused by ATX II. Conclusion: The mexiletine can be used to treat LQT_3.