title: Basis for the Induction of Tissue-Level Phase-2 Reentry as a Repolarization Disorder in the Brugada Syndrome.
abstract: OBJECTIVE
  Human action potentials in the Brugada syndrome have been characterized by delayed or even complete loss of dome formation, especially in the right ventricular epicardial layers. Such a repolarization pattern is believed to trigger phase-2 reentry (P2R); however, little is known about the conditions necessary for its initiation. This study aims to determine the specific mechanisms that facilitate P2R induction in Brugada-affected cardiac tissue in humans.
  
  
  METHODS
  Ionic models for Brugada syndrome in human epicardial cells were developed and used to study the induction of P2R in cables, sheets, and a three-dimensional model of the right ventricular free wall.
  
  
  RESULTS
  In one-dimensional cables, P2R can be induced by adjoining lost-dome and delayed-dome regions, as mediated by tissue excitability and transmembrane voltage profiles, and reduced coupling facilitates its induction. In two and three dimensions, sustained reentry can arise when three regions (delayed-dome, lost-dome, and normal epicardium) are present.
  
  
  CONCLUSIONS
  Not only does P2R induction by Brugada syndrome require regions of action potential with delayed-dome and lost-dome, but in order to generate a sustained reentry from a triggered waveback multiple factors are necessary, including heterogeneity in action potential distribution, tissue coupling, direction of stimulation, the shape of the late plateau, the duration of lost-dome action potentials, and recovery of tissue excitability, which is predominantly modulated by tissue coupling.
authors.affiliation: Department of Computer Science, University of Oxford, Oxford OX1 3QD, UK.
authors.forename: Alfonso
authors.initials: A
authors.lastname: Bueno-Orovio
authors.affiliation: School of Mathematical Sciences, Rochester Institute of Technology, Rochester, NY 14623-5603, USA.
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Cherry
authors.affiliation: The Heart Institute, Beth Israel Medical Center, New York, NY 10003, USA.
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Evans
authors.affiliation: School of Physics, Georgia Institute of Technology, Atlanta, GA 30332-0430, USA ; School of Biology, Georgia Institute of Technology, Atlanta, GA 30332-2230, USA ; School of Applied Physiology, Georgia Institute of Technology, Atlanta, GA 30332-0356, USA.
authors.forename: Flavio H
authors.initials: FH
authors.lastname: Fenton
mesh_terms: D000200:Action Potentials / Q000502:physiology*; D053840:Brugada Syndrome / Q000503:physiopathology*; D003198:Computer Simulation; D004562:Electrocardiography / Q000379:methods*; D006352:Heart Ventricles / Q000503:physiopathology*; D006801:Humans; D008955:Models, Cardiovascular; D010496:Pericardium / Q000503:physiopathology; D014693:Ventricular Fibrillation / Q000503:physiopathology