Accurate detection of drug-induced delayed ventricular repolarization with a suitable correction formula in Langendorff guinea pig heart.

摘要: The aims of this study were to determine a suitable method correct the ventricular repolarization period against RR interval in isolated perfused Langendorff guinea pig heart and clarify reliability model using several drugs. QT intervals from an electrocardiogram epicardial monophasic action potential duration (MAP(90)) measured. Two drugs clinically known be QT-prolonging (E-4031, moxifloxacin) two non-QT-prolonging (verapamil, zatebradine) used for study. To correcting interval, rates slowed with 0.3 µM zatebradine, specific bradycardiac agent, then accelerated atrial pacing obtain wide range MAP(90)/RR relationships. An exponential rate-correction elicited most appropriate algorithm relationship among four models tested. Based on linear regression analysis, showed superior dissociation corrected MAP(90)s than generic Bazett's Fridericia's formulae. E-4031 moxifloxacin prolonged (QTc) MAP(90) under at cycle length 0.25 sec (MAP(90(pacing))) dose-dependently; verapamil zatebradine failed prolong them, indicating that was excellent. MAP(90(pacing)) prolongation by moxifloxacin, positive compound clinical "Thorough QT/QTc Study", seen around QTc-prolonging concentrations clinic, suggesting sensitivity would evaluation. We therefore concluded is sufficiently sensitive useful assessing