奎尼丁诱发尖端扭转型室性心动过速的兔离体研究

Quinidine Induced Torsade De Pointes in Isolated Rabbit Heart

目的:应用奎尼丁在兔离体心脏诱发尖端扭转型室性心动过速(TdP),并探讨其发病机制。方法:制作兔离体心脏Ⅲ度房室传导阻滞(AVB),利用Langendorff逆灌流技术,应用奎尼丁低钾镁台氏液灌流,诱发TdP。结果:14只兔离体心脏在台氏液和低钾镁台氏液灌流下,均未见早期后除极(EADs)、触发活动(TA)及TdP;低钾镁台氏液灌流,在400～1200ms起搏下,奎尼丁可浓度依赖性延长QT间期和APD90。在起搏周长≥1400ms时,12只离体心脏观察到EADs,13只诱发出TA;自主节律或2400ms起搏下,10只离体心脏共诱发TdP(5～23次心搏)发作185次且均能自行终止;以1×10-6mol/L诱发只数和次数最多。结论:在兔离体心脏,慢频率起搏或缓慢自主节律下奎尼丁低钾镁台氏液灌注可反复诱发TdP;EADs引起的TA是发生TdP的基础;1×10-6mol/L奎尼丁诱发TdP的作用最明显。

Objective： To investigate the mechanism of Torsade de poindes （TdP） by perfusion quindine in isolated rabbit heart. Methods： The models of Langendorff perfused isolated rabbit hearts （n = 14 ） with cauterize-induced Ⅲ° atrio-ventricular block （Ⅲ° AVB ） were made. The TdP was induced with the perfusion of quinidine and low potassium and magnesium. Results： No early after depolarizations （EADs）,triggered activity （TA） and TdP were induced with tyrodes solution and modified tyrode＇s solution perfusion in 14 isolated rabbit hearts. Quinidine prolonged QT interval and APD90 at different concentration compared with baseline when pacing cycle length （CL） was from 400 ms to 1 200 ms. When CL was more than 1 400 ms, EADs were observed in 12/14（85.7%） isolated hearts and triggers with 1 to 4 heart beats were induced in 13/14 （92.8%） isolated hearts. The TdP（5-23 beats） ensued repeatedly with quinidine （concentration was 1×10^-6,5×10^-6, and 1×10^-6mol/L,respectively） concurrently with modified tyrode＇s solution in 10/14 （71.4%） hearts studied while the spontaneous heart rate was slowly or pacing CL was 2 400 ms. A total of 185 episodes of TdP were induced. All episodes of TdP terminated spontaneously. Episodes of TdP induced were the most when the concentration of quinidine was 1×10^-6 mol/L （93 episodes,50% ）. Conclusion： In this study of l_angendorff perfused rabbit hearts,TdP can be induced by means of bradycardia in the presence of quinidine in the modified tyrode＇ s solution. EADs were associated with TdP. There was an obvious effect of quinidine on TdP in the lowest concentration.