14th International Congress
THE "NEW FRONTIERS"
OF ARRHYTHMIAS 2000

Jan. 29 - Feb. 5, 2000
Marilleva, Trento, Italy

RT-80

The contribution of disorders of cardiac repolarization to arrhythmogenesis in the long QT syndrome

Nabil El-Sherif, Dmitry O. Kozhevnikov, Gioia Turitto.
Cardiology Division, Department of Medicine, State University of New York Health Science Center and Department of Veterans Affairs New York Harbor Health Care System, Brooklyn, New York, USA

Introduction

For over a decade, El-Sherif and associates have developed an in vivo canine model of LQTS and TdP using the neurotoxins anthopleurin-A (AP-A) or ATX-II^1-8. These agents act by slowing Na channel inactivation resulting in a sustained inward current during the plateau and prolongation of the action potential duration (APD)^3,4. The model anticipated the more recent discovery of a genetic mutation of the Na channel subunit (SCN5A) in patients with LQT3⁹. The mutant channels were shown to generate a sustained inward current during depolarization quite similar to the Na channel exposed to AP-A or ATX-II¹⁰. Although the model is a surrogate of LQT3 which is a relatively uncommon form of congenital LQTS, the basic electrophysiologic mechanism of TdP in this model seems to apply, with some necessary modifications, to all forms of congenital and acquired LQTS. In a series of reports, a paradigm of the mechanisms of TdP that extends from an ion channel abnormality to an arrhythmia with a characteristic ECG morphology was elucidated^1-8. In this report the contribution of disorders of cardiac repolarization to arrhythmogenesis in the long QT syndrome will be reviewed. A more detailed review was recently published¹¹.

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