Electrophysiological mechanisms of ventricular arrhythmias associated with QT interval prolongation

动物实验研究了抗心律失常药物和甲状腺功能减退导致室性心律失常QT间期延长的电生理机制。在langendorff灌注兔心脏中，bepridil （1 M）引起远端双极心电图（DBEs） QT间期明显延长。10时，QT延长进一步增强，QRS持续时间也明显延长。多态性室性心动过速常由单次高浓度过早刺激引起。在改良双极电极记录的心外膜电图中，bepridil延长了QRS复合物负偏转峰到T波顶点（Q-aT）的间隔时间，这与90%复极时细胞内动作电位持续时间（APD）相对应。Q-aT在基部的延长比在顶端的延长大，导致了明显的复极化畸变和弥散。当贝必地尔浓度较高时，心外膜表面的复极离散度因激活延迟而明显增强。这些结果表明，贝比地尔引起心室肌APD的区域不同延长，导致复极的时间离散度增加，并且当毒性剂量伴随缓慢传导时，这种离散度可能诱导再入性心律失常。研究了甲状腺切除术后4 ~ 6周兔右心室乳头肌的机电特性。甲状腺切除术导致APD和发展张力（DT）达到峰值的时间显著延长。在甲状腺功能减退的心室肌中，ryanodine敏感的收缩成分如休息后增强在很大程度上被抑制。这些结果表明，APD延长心室肌伴甲状腺功能减退导致QT延长可能至少部分归因于细胞内钙动力学的抑制。少

Electrophysiological mechanisms of ventricular arrhythmias associated with QT interval prolongation by antiarrhythmic drugs and hypothyroidism were investigated in animal experiments. In Langendorff-perfused rabbit hearts, bepridil (1 M) caused a significant prolongation of QT interval of distant bipolar electrograms (DBEs). At 10 ,, the QT prolongation was further enhanced, and a significant prolongation of QRS duration was also observed. Polymorphous ventricular tachycardia was frequently induced by a single premature stimulus at the higher concentration. In epicardial electrograms recorded through modified bipolar electrodes, bepridil prolonged the interval from the peak negative deflection of the QRS complex to the apex of the T wave (Q-aT), which corresponded to the intracellular action potential duration (APD) at 90 % repolarization. The Q-aT prolongation was larger in the base than in the apex, resulting in a marked distortion and dispersion of repolarization. At the higher conc … More entration of bepridil, the dispersion of repolarization was much more enhanced by activation delay in the epicardial surface. These findings suggest that bepridil causes regionally different lengthening of APD in ventricular muscle leading to an increase in temporal dispersion of repolarization, and that this dispersion may be inductive for re-entrant arrhythmias when accompanied by slow conduction at toxic dose. Electromechanical characteristics of right ventricular papillary muscles isolated from rabbits 4 to 6 weeks after thyroidectomy were also investigated. Thyroidectomy resulted in a marked prolongation of both APD and the time to peak developed tension (DT). Ryanodine-sensitive components of contraction such as post-rest potentiation were largely inhibited in ventricular muscles of hypothyroidism. These results suggest that APD prolongation of ventricular muscles with hypothyroidism leading to a QT prolongation may be attributed at least in part to an inhibition of intracellular calcium dynamics. Less