NDLI: Dofetilide unmasks occult congenital long QT syndrome type 2: A simulation study

Content Provider	IEEE Xplore Digital Library
Author	Romero, L. Trenor, B. Ferrero, J.M. Saiz, J. Clancy, C.E.
Copyright Year	2012
Description	Author affiliation: Department of Pharmacology, University of California Davis, Davis, USA (Clancy, C.E.) \|\| I3BH, Universitat Politècnica de València, Valencia, Spain (Romero, L.; Trenor, B.; Ferrero, J.M.; Saiz, J.)
Abstract	Accurate diagnosis of long QT syndrome is a key factor for reducing the risk of cardiac arrhythmias. Our goal is to investigate the potential use of dofetilide to unmask latent IKr mutation carriers. A modified version of the O'Hara et al. model was used to simulate the electrical activity of isolated cardiac cells. The original IKr formulation was replaced by the Fink et al. Markov model of the human IKr channels and our dynamic model of dofetilide was used to simulate drug administration. A sensitivity analysis was performed to study the effect of IKr transition rate alterations on AP duration (APD) prolongation in the absence and in the presence of dofetilide. Our results show that acceleration of the rate transition from open to the last closed state (ββ) produced the shortest prolongation of the APD in the absence of the drug. However, ββ acceleration provoked the highest additional APD prolongation under dofetilide exposure related to the APD prolongation observed before the drug application. In addition, this IKr alteration was the transition rate modification that most increased the rate of deactivation. In conclusion, our observations indicate that dofetilide could potentially be used to unmask IKr mutations accelerating the deactivation process.
Starting Page	845
Ending Page	848
File Size	363576
Page Count	4
File Format	PDF
ISBN	9781467320764
ISSN	2325887X
e-ISBN	9781467320771
Language	English
Publisher	Institute of Electrical and Electronics Engineers, Inc. (IEEE)
Publisher Date	2012-09-09
Publisher Place	Poland
Access Restriction	Subscribed
Rights Holder	Creative Commons Attribution License 2.5 (CCAL)
Subject Keyword	Acceleration Drugs Humans Steady-state Electric potential Markov processes Genetics
Content Type	Text
Resource Type	Article
Subject	Computer Science Cardiology and Cardiovascular Medicine

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