title: Dependence of phase-2 reentry and repolarization dispersion on epicardial and transmural ionic heterogeneity: a simulation study.
abstract: OBJECTIVE
  Phase-2 reentry (P2R) is a local arrhythmogenic phenomenon where electrotonic current propagates from a spike-and-dome action potential region to re-excite a loss-of-dome action potential region. While ionic heterogeneity has been shown to underlie P2R within the epicardium and has been hypothesized to occur transmurally, we are unaware of any study that has investigated the effects of combining these heterogeneities as they occur in the heart. Thus, we tested the hypothesis that P2R can result by either epicardial or transmural heterogeneity and that the realistic combination of the two would increase the likelihood of P2R.
  
  
  RESULTS
  We used computational ionic models of cardiac myocyte dynamics to investigate initiation and development of P2R in simulated tissues with different ionic heterogeneities. In one-dimensional transmural cable simulations, P2R occurred when the conductance of the transient outward current in the epicardial region was near the range for which epicardial action potentials switched intermittently between spike-and-dome and loss-of-dome morphologies. Phase-2 reentry was more likely in two-dimensional tissue simulations by both epicardial and transmural heterogeneity and could expand beyond its local initiation site to create a macroscopic reentry.
  
  
  CONCLUSIONS
  The characteristics and stability of action potential morphology in the epicardium are important determinants of the occurrence of both transmural and epicardial P2R and its associated arrhythmogenesis.
authors.affiliation: Greenberg Division of Cardiology, Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA.
authors.forename: Anat
authors.initials: A
authors.lastname: Maoz
authors.forename: David J
authors.initials: DJ
authors.lastname: Christini
authors.forename: Trine
authors.initials: T
authors.lastname: Krogh-Madsen
mesh_terms: D000200:Action Potentials; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000503:physiopathology*; D003198:Computer Simulation; D006329:Heart Conduction System / Q000503:physiopathology*; D006801:Humans; D015640:Ion Channel Gating; D008955:Models, Cardiovascular; D032342:Muscle Cells / Q000378:metabolism*; D010496:Pericardium / Q000503:physiopathology*
keywords: Brugada syndrome; Computer modelling; Ionic heterogeneity; Phase-2 reentry; Transient outward current