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Isolated tissue models and proarrhythmia

M.R. Rosen*

Departments of Pharmacology and Pediatrics, College of Physicians and Surgeons of Columbia University, New York, U.S.A.

* Correspondence: Michael R. Rosen, MD, Gustavus A. Pfeiffer Professor of Pharmacology and Professor of Pediatrics, College of Physicians & Surgeons of Columbia University, Department of Pharmacology, 630 West 168 Street, PH7W-321, New York, NY 10032, U.S.A.

Abstract

Awareness of QT prolongation and torsades de pointes resulting from non-cardiac drug administration has stressed the need for screening procedures to limit development of drugs whose repolarization profile denotes excess risk. This paper focuses on isolated tissue screens, although the linkages of these with molecular/biophysical and intact animal screens is discussed as well. It is suggested that the use of single models, while promoting definitive conclusions, may increase the incidence of incorrect decisions (due to narrowness of focus). Rather, the use of several models/screens is suggested to be most likely to facilitate accurate decision-making.

Key Words: Acquired long QT syndrome • torsades de pointes • early afterdepolarizations • delayed rectifier current


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