title: Interaction of specialized cardiac conduction system with antiarrhythmic drugs: a simulation study.
abstract: The use of antiarrhythmic drugs is common to treat heart rhythm disorders. Computational modeling and simulation are promising tools that could be used to investigate the effects of specific drugs on cardiac electrophysiology. In this paper, we study the multiscale effects of dofetilide, a drug that blocks IKr, from cellular to organ level paying special attention to its effect on heart structures, in particular the specialized cardiac conduction system (CCS). We include a model of the CCS in a patient-specific anatomical ventricular model and study the drug effects in simulations with and without a CCS. Results confirmed the expected effects of dofetilide at cellular level, increasing the action potential duration, and at organ level, prolonging the QT segment. Notable differences are shown between models with and without the CCS on action potential duration distributions. These techniques show the importance of heart heterogeneity and the global effects of the interaction of drugs with cardiac structures.
authors.affiliation: Department of Electronic Engineering, Universitat Politècnica de València, Valencia 46022, Spain. lduxsantoy@gbio.i3bh.es
authors.forename: Lydia
authors.initials: L
authors.lastname: Dux-Santoy
authors.forename: Rafael
authors.initials: R
authors.lastname: Sebastian
authors.forename: Jose
authors.initials: J
authors.lastname: Felix-Rodriguez
authors.forename: Jose Maria
authors.initials: JM
authors.lastname: Ferrero
authors.forename: Javier
authors.initials: J
authors.lastname: Saiz
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D003198:Computer Simulation; D056324:Diffusion Tensor Imaging; D015195:Drug Design; D004562:Electrocardiography; D006329:Heart Conduction System / Q000033:anatomy & histology / Q000187:drug effects* / Q000502:physiology; D006352:Heart Ventricles / Q000187:drug effects; D006801:Humans; D008955:Models, Cardiovascular; D010627:Phenethylamines / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology
chemical_list: D000889:Anti-Arrhythmia Agents; D010627:Phenethylamines; D013449:Sulfonamides; C063533:dofetilide