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Current Cardiology Reviews

Editor-in-Chief

ISSN (Print): 1573-403X
ISSN (Online): 1875-6557

A Combined Approach Using Patch-Clamp Study and Computer Simulation Study for Understanding Long QT Syndrome and TdP in Women

Author(s): Tetsushi Furukawa, Junko Kurokawa and Colleen E. Clancy

Volume 4, Issue 4, 2008

Page: [244 - 250] Pages: 7

DOI: 10.2174/157340308786349507

Price: $65

Abstract

Female sex is an independent risk factor for development of torsade de pointes (TdP)-type arrhythmias in both congenital and acquired long QT syndrome (LQTS). In females, QTc interval and TdP risk vary during the menstrual cycle and around delivery. Biological experiments including single-cell current recordings with the patch-clamp technique and biochemical experiments show that progesterone modulates cardiac K+ current and Ca2+ current via the non-genomic pathway of the progesterone receptor, and thus the cardiac repolarization duration, in a concentration-dependent manner. Incorporation of these biological findings into a computer model of single-cell and coupled-cell cardiomyocytes simulates fluctuations in QTc interval during the menstrual cycle with reasonable accuracy. Based on this model, progesterone is predicted to have protective effects against sympathetic nervous system-induced arrhythmias in congenital LQTS and drug-induced TdP in acquired LQTS. A combined biological and computational approach may provide a powerful means to risk stratify TdP risk in women.

Keywords: Long QT syndrome, sex hormone, nitric oxide, arrhythmia, patch-clamp, non-genomic pathway


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