title: Virtual cell and tissue dynamics of ectopic activation of the ventricles.
abstract: Cardiac ventricular cells and tissues are normally excitable, and are activated by propagating waves of excitation that are initiated in the specialized pacemaking region of the heart. However, isolated or repetitive activity can be initiated at abnormal (ectopic) sites in the ventricles. To trigger an endogenous ectopic beat, there must be a compact focus of cells with changed membrane excitation parameters and kinetics, which initiate activity by after-depolarizations triggered by propagating activity, or that have bifurcated into autorhythmicity. This ectopic focus needs to be large enough, and adequately coupled, to drive the surrounding tissue. We investigate the initiation of ectopic excitation in computational models of human ventricular cells triggered by after-depolarizations and by up/down regulation of specific membrane conductance systems, and the propagation and evolution of ectopic activity in homogeneous or heterogeneous and isotropic, anisotropic, or orthotropic tissues.
authors.affiliation: Computational Biology Laboratory, Institute of Membrane and Systems Biology, and Cardiovascular Research Institute, Worsley Building, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, United Kingdom.
authors.forename: Alan P
authors.initials: AP
authors.lastname: Benson
authors.forename: Graeme
authors.initials: G
authors.lastname: Halley
authors.forename: Pan
authors.initials: P
authors.lastname: Li
authors.forename: Wing C
authors.initials: WC
authors.lastname: Tong
authors.forename: Arun V
authors.initials: AV
authors.lastname: Holden
mesh_terms: D000200:Action Potentials; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000503:physiopathology*; D001683:Biological Clocks; D003198:Computer Simulation; D006329:Heart Conduction System / Q000503:physiopathology*; D006352:Heart Ventricles / Q000503:physiopathology*; D006801:Humans; D008955:Models, Cardiovascular; D009200:Myocardial Contraction; D032383:Myocytes, Cardiac; D009991:Oscillometry / Q000379:methods