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目的观察辛伐他汀在正常及晚钠电流(INa-L)增大的情况下对离体兔左室心电活动的影响。方法建立经冠状动脉灌注兔左室楔形组织块标本。实验分为两部分:正常情况组:以自身空白作对照,依次给予10、30、100nmol/L浓度的辛伐他汀;INa-L增大组:使用海葵毒素(ATX-II)建立INa-L增大模型后,依次给予10、30、100nmol/L浓度的辛伐他汀。记录各组跨壁心电图及动作电位,观察QRS波宽度、QT间期、T波峰值至终点的时程(Tp-e)、Tp-e/QT及动作电位复极90%时程(APD90)在上述分组中的变化,以及是否引发早期后除极(EAD)和尖端扭转型室性心动过速(TdP)。结果 (1)在正常情况下,辛伐他汀在10、30、100nmol/L浓度下对QRS波宽度、QT间期、Tp-e间期、Tp-e/QT、APD90均无明显影响(P>0.05)。(2)INa-L增大后,10nmol/L辛伐他汀对上述电生理指标无明显影响(P>0.05),30nmol/L及100nmol/L辛伐他汀则显著延长QT间期和APD90(P<0.01),同时减小Tp-e/QT(P<0.05)。且未见EAD及TdP发生。结论在正常情况下,辛伐他汀对兔离体左室除极及复极活动无明显影响;INa-L增大后,高于治疗浓度的辛伐他汀可延长复极时程,同时显著减小跨壁复极离散度,从而降低致心律失常风险。
Objective To observe the effect of simvastatin on left ventricular (LV) left ventricular electrical activity in isolated rabbit under normal and late sodium currents (INa-L). Methods Rabbit left ventricular wedge tissue specimens were perfused via coronary artery. The experiment was divided into two parts: In normal group, simvastatin at 10, 30 and 100nmol / L was given as a control; INa-L increased group: INA-II was used to establish INa- L increased the model, followed by 10,30,100 nmol / L concentration of simvastatin. The cross-sectional electrocardiogram (ECG) and action potential of each group were recorded. The QRS duration, QT interval, Tp-e, Tp-e / QT and APD 90% Changes in the above subgroups, as well as whether initiating EAD and TdP. Results (1) Under normal conditions, simvastatin had no significant effect on QRS width, QT interval, Tp-e interval, Tp-e / QT and APD90 at concentrations of 10, 30 and 100 nmol / L > 0.05). (2) After INa-L increased, simvastatin 10nmol / L had no significant effect on the above electrophysiological parameters (P> 0.05). Simvastatin at 30nmol / L and 100nmol / L significantly prolonged the QT interval and APD90 <0.01), while decreasing Tp-e / QT (P <0.05). And no EAD and TdP occurred. Conclusion Under normal conditions, simvastatin has no significant effect on isolated rabbit left ventricular depolarization and repolarization activity. After INa-L increases, simvastatin above the therapeutic concentration prolongs repolarization duration and decreases significantly Small cross-wall repolarization dispersion, thereby reducing the risk of arrhythmia.