Title :
Sex and age related differences in drug induced QT prolongation by dofetilide under reduced repolarization reserve in simulated ventricular cells
Author :
Gonzalez, Rodolfo ; Gomis-Tena, Julio ; Corrias, Alberto ; Ferrero, Jose Maria ; Rodriguez, Blanca ; Saiz, Javier
Author_Institution :
Dept. de Ing. Electron., Inst. Tecnol. de Morelia, Morelia, Mexico
fDate :
Aug. 31 2010-Sept. 4 2010
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.
Keywords :
bioelectric potentials; cardiovascular system; cellular biophysics; drugs; physiological models; action potentials; adult female cells; age related differences; class III antiarrhythmic drug; dofetilide; drug induced QT prolongation; left ventricular endocardial action potentials; modified Luo Rudy model; repolarization reserve; sex; simulated ventricular cells; steeper APD-BCL relationship; susceptibility; Cardiology; Drugs; Electric potential; Heart; Indium tin oxide; Mathematical model; Rectifiers; Action Potentials; Aging; Anti-Arrhythmia Agents; Computer Simulation; Female; Heart Conduction System; Heart Ventricles; Humans; Long QT Syndrome; Male; Models, Cardiovascular; Myocytes, Cardiac; Phenethylamines; Sex Factors; Sulfonamides;
Conference_Titel :
Engineering in Medicine and Biology Society (EMBC), 2010 Annual International Conference of the IEEE
Conference_Location :
Buenos Aires
Print_ISBN :
978-1-4244-4123-5
DOI :
10.1109/IEMBS.2010.5627415