title: Dispersion of cardiac action potential duration and the initiation of re-entry: a computational study.
abstract: BACKGROUND
  The initiation of re-entrant cardiac arrhythmias is associated with increased dispersion of repolarisation, but the details are difficult to investigate either experimentally or clinically. We used a computational model of cardiac tissue to study systematically the association between action potential duration (APD) dispersion and susceptibility to re-entry.
  
  
  METHODS
  We simulated a 60 x 60 mm2 D sheet of cardiac ventricular tissue using the Luo-Rudy phase 1 model, with maximal conductance of the K+ channel gKmax set to 0.004 mS mm(-2). Within the central 40 x 40 mm region we introduced square regions with prolonged APD by reducing gKmax to between 0.001 and 0.003 mS mm(-2). We varied (i) the spatial scale of these regions, (ii) the magnitude of gKmax in these regions, and (iii) cell-to-cell coupling.
  
  
  RESULTS
  Changing spatial scale from 5 to 20 mm increased APD dispersion from 49 to 102 ms, and the susceptible window from 31 to 86 ms. Decreasing gKmax in regions with prolonged APD from 0.003 to 0.001 mS mm-2 increased APD dispersion from 22 to 70 ms, and the susceptible window from <1 to 56 ms. Decreasing cell-to-cell coupling by changing the diffusion coefficient from 0.2 to 0.05 mm2 ms(-1) increased APD dispersion from 57 to 88 ms, and increased the susceptible window from 41 to 74 ms.
  
  
  CONCLUSIONS
  We found a close association between increased APD dispersion and susceptibility to re-entrant arrhythmias, when APD dispersion is increased by larger spatial scale of heterogeneity, greater electrophysiological heterogeneity, and weaker cell-to-cell coupling.
authors.affiliation: Department of Computer Science, University of Sheffield, UK. r.h.clayton@sheffield.ac.uk
authors.forename: Richard H
authors.initials: RH
authors.lastname: Clayton
authors.forename: Arun V
authors.initials: AV
authors.lastname: Holden
mesh_terms: D000200:Action Potentials; D000818:Animals; D003198:Computer Simulation; D004198:Disease Susceptibility / Q000503:physiopathology; D004562:Electrocardiography / Q000379:methods; D006329:Heart Conduction System / Q000503:physiopathology*; D006352:Heart Ventricles / Q000503:physiopathology*; D006801:Humans; D008564:Membrane Potentials; D008955:Models, Cardiovascular; D017180:Tachycardia, Ventricular / Q000503:physiopathology*; D014693:Ventricular Fibrillation / Q000503:physiopathology*
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