Electrophysiological mechanisms of ventricular arrhythmias associated with QT interval prolongation

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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