Transmural dispersion of repolarization as a key factor of arrhythmogenicity in a novel intact heart model of LQT3

Abstract

Background: Congenital and acquired long QT syndrome (LQTS) are caused by abnormalities of ionic currents underlying ventricular repolarization. For a better understanding of the mechanisms by which functional electrical instability at the level of the whole heart leads to torsade de pointes (TdP), a novel model of LQT3 was developed and the role of transmural dispersion of repolarization for the development of proarrhythmia was evaluated. Methods and results: In 11 Langendorff-perfused rabbit hearts, veratridine (0.1–0.5 μM), an inhibitor of sodium channel inactivation, led to a concentration-dependent increase in QT-interval and simultaneously recorded monophasic ventricular action potentials (MAPs) (pppConclusion: By inhibition of sodium channel inactivation, veratridine mimics LQT3 in this intact heart model. In bradycardic, hypokalemic hearts, it reproducibly induced EADs and TdP in the setting of significantly increased left ventricular transmural dispersion of repolarization. Based on these experimental data, reduction of transmural dispersion of repolarization may be considered an important target for the prevention of TdP in patients with LQT3.