NDLI: Sex and age related differences in drug induced QT prolongation by dofetilide under reduced repolarization reserve in simulated ventricular cells

Content Provider	IEEE Xplore Digital Library
Author	Gonzalez, R. Gomis-Tena, J. Corrias, A. Ferrero, J.M. Rodriguez, B. Saiz, J.
Copyright Year	2010
Description	Author affiliation: Departamento de Ingeniería Electrónica, Instituto Tecnológico de Morelia, Mexico (Gonzalez, R.) \|\| Computing Laboratory, Oxford University, U.K. (Corrias, A.; Rodriguez, B.) \|\| i3BH, Universidad Politécnica de Valencia, Spain (Gomis-Tena, J.; Ferrero, J.M.; Saiz, J.)
Abstract	The aim of this study was to investigate sex and age related differences in drug induced QT prolongation by dofetilide under reduced repolarization reserve in simulated ventricular cells. Left ventricular endocardial action potentials were simulated using a modified Luo Rudy model. Sex, age and regional differences in currents ICaL, IKr, IKs, and Ito were incorporated into the model by modifying the equations representing them. A model of dofetilide, a class III antiarrhythmic drug, was developed and included into a ventricular cell models. The reduced repolarization reserve was reproduced decreasing the IKs current. Our results shown that the adult female cells had longer action potentials, a steeper APD-BCL relationship and a higher susceptibility to EADs than adult male cells, under control, drug induced and reduced repolarization reserve conditions. On the other hand, young female and young male cells had similar action potentials under control conditions. However, young male cells had longer action potentials and higher susceptibility to EADs than young female cells under drug induced and reduced repolarization reserve conditions. Sex and age dependent differences in ICaL, IKr, IKs, and Ito may explain the age and sex disparities in prolongation of APD by the action of dofetilide.
Starting Page	3245
Ending Page	3248
File Size	1076124
Page Count	4
File Format	PDF
ISBN	9781424441235
ISSN	1557170X
DOI	10.1109/IEMBS.2010.5627415
Language	English
Publisher	Institute of Electrical and Electronics Engineers, Inc. (IEEE)
Publisher Date	2010-08-31
Publisher Place	Argentina
Access Restriction	Subscribed
Rights Holder	Institute of Electrical and Electronics Engineers, Inc. (IEEE)
Subject Keyword	Drugs Electric potential Mathematical model Indium tin oxide Heart Rectifiers Cardiology
Content Type	Text
Resource Type	Article
Subject	Signal Processing Biomedical Engineering Health Informatics Computer Vision and Pattern Recognition

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4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
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