Comparison of sensitivity of surrogate markers of drug-induced torsades de pointes in canine hearts.

摘要

Given a limited information regarding the difference of the sensitivity of surrogate markers of drug-induced torsades de pointes, including early afterdepolarization, ectopic beats, phase 3 repolarization and dispersion of ventricular repolarization, we simultaneously analyzed them in the halothane-anesthetized canine model (n=5). A non-specific I(Kr) channel blocker sparfloxacin, which has been known to induce torsades de pointes in animals and clinical patients, prolonged the repolarization process in a dose-related and reverse use-dependent manner. No significant change was detected in any of the proarrhythmic markers except for the backward parallel shift of phase 3 repolarization in the cardiac cycle with the QT interval prolongation, which would be the most sensitive marker in predicting the potential arrhythmogenic property of sparfloxacin in the non-remodeled