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, Colleen E. Clancy.

Journal Name: Current Cardiology Reviews

Volume 4 , Issue 4 , 2008

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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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Article Details

VOLUME: 4
ISSUE: 4
Year: 2008
Page: [244 - 250]
Pages: 7
DOI: 10.2174/157340308786349507
Price: $58

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