title: Virtual tissue engineering of the human atrium: modelling pharmacological actions on atrial arrhythmogenesis.
abstract: Computational models of human atrial cells, tissues and atria have been developed. Cell models, for atrial wall, crista terminalis, appendage, Bachmann's bundle and pectinate myocytes are characterised by action potentials, ionic currents and action potential duration (APD) restitution. The principal effect of the ion channel remodelling of persistent atrial fibrillation (AF), and a mutation producing familial AF, was APD shortening at all rates. Electrical alternans was abolished by the modelled action of Dronedarone. AF induced gap junctional remodelling slows propagation velocity at all rates. Re-entrant spiral waves in 2-D models are characterised by their frequency, wavelength, meander and stability. For homogenous models of normal tissue, spiral waves self-terminate, due to meander to inexcitable boundaries, and by dissipation of excitation. AF electrical remodelling in these homogenous models led to persistence of spiral waves, and AF fibrotic remodelling to their breakdown into fibrillatory activity. An anatomical model of the atria was partially validated by the activation times of normal sinus rhythm. The use of tissue geometry from clinical MRI, and tissue anisotropy from ex vivo diffusion tensor magnetic resonance imaging is outlined. In the homogenous model of normal atria, a single scroll breaks down onto spatio-temporal irregularity (electrical fibrillation) that is self-terminating; while in the AF remodelled atria the fibrillatory activity is persistent. The persistence of electrical AF can be dissected in the model in terms of ion channel and intercellular coupling processes, that can be modified pharmacologically; the effects of anatomy, that can be modified by ablation; and the permanent effects of fibrosis, that need to be prevented.
authors: Biological Physics Group, School of Physics and Astronomy, University of Manchester, Manchester M13 9PL, United Kingdom.
authors: Oleg V
authors: OV
authors: Aslanidi
authors: Moza
authors: M
authors: Al-Owais
authors: Alan P
authors: AP
authors: Benson
authors: Michael
authors: M
authors: Colman
authors: Clifford J
authors: CJ
authors: Garratt
authors: Stephen H
authors: SH
authors: Gilbert
authors: John P
authors: JP
authors: Greenwood
authors: Arun V
authors: AV
authors: Holden
authors: Sanjay
authors: S
authors: Kharche
authors: Elizabeth
authors: E
authors: Kinnell
authors: Eleftheria
authors: E
authors: Pervolaraki
authors: Sven
authors: S
authors: Plein
authors: Jonathan
authors: J
authors: Stott
authors: Henggui
authors: H
authors: Zhang
mesh_terms: D000200:Action Potentials; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001145:Arrhythmias, Cardiac / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D016275:Atrial Function / Q000187:drug effects*; D003198:Computer Simulation; D056324:Diffusion Tensor Imaging; D005355:Fibrosis; D020022:Genetic Predisposition to Disease; D006325:Heart Atria / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D008955:Models, Cardiovascular; D009154:Mutation; D010641:Phenotype; D049490:Systems Biology; D013997:Time Factors; D014584:User-Computer Interface
chemical_list: D000889:Anti-Arrhythmia Agents