title: Electrophysiological properties of computational human ventricular cell action potential models under acute ischemic conditions.
abstract: Acute myocardial ischemia is one of the main causes of sudden cardiac death. The mechanisms have been investigated primarily in experimental and computational studies using different animal species, but human studies remain scarce. In this study, we assess the ability of four human ventricular action potential models (ten Tusscher and Panfilov, 2006; Grandi et al., 2010; Carro et al., 2011; O'Hara et al., 2011) to simulate key electrophysiological consequences of acute myocardial ischemia in single cell and tissue simulations. We specifically focus on evaluating the effect of extracellular potassium concentration and activation of the ATP-sensitive inward-rectifying potassium current on action potential duration, post-repolarization refractoriness, and conduction velocity, as the most critical factors in determining reentry vulnerability during ischemia. Our results show that the Grandi and O'Hara models required modifications to reproduce expected ischemic changes, specifically modifying the intracellular potassium concentration in the Grandi model and the sodium current in the O'Hara model. With these modifications, the four human ventricular cell AP models analyzed in this study reproduce the electrophysiological alterations in repolarization, refractoriness, and conduction velocity caused by acute myocardial ischemia. However, quantitative differences are observed between the models and overall, the ten Tusscher and modified O'Hara models show closest agreement to experimental data.
authors.affiliation: Department of Computer Science, University of Oxford, Oxford, UK. Electronic address: sara.dutta@cs.ox.ac.uk.
authors.forename: Sara
authors.initials: S
authors.lastname: Dutta
authors.affiliation: Department of Computer Science, University of Oxford, Oxford, UK.
authors.forename: Ana
authors.initials: A
authors.lastname: Mincholé
authors.affiliation: Department of Physiology and Biophysics, Dalhousie University, Halifax, Canada.
authors.forename: T Alexander
authors.initials: TA
authors.lastname: Quinn
authors.affiliation: Department of Computer Science, University of Oxford, Oxford, UK.
authors.forename: Blanca
authors.initials: B
authors.lastname: Rodriguez
mesh_terms: D000200:Action Potentials; D000208:Acute Disease; D006352:Heart Ventricles / Q000473:pathology*; D006801:Humans; D008955:Models, Cardiovascular; D017202:Myocardial Ischemia / Q000473:pathology* / Q000503:physiopathology
keywords: Action potential duration; Arrhythmias; Conduction velocity; Human ventricular cell models; Myocardial ischemia; Refractory period