title: Mechanism underlying initiation of paroxysmal atrial flutter/atrial fibrillation by ectopic foci: a simulation study.
abstract: BACKGROUND
  The mechanisms underlying paroxysmal atrial flutter/atrial fibrillation initiation by ectopic foci from various locations are unclear.
  
  
  RESULTS
  We used parallel computational techniques to study an anatomically accurate 3-dimensional atrial structure incorporating a detailed ionic-current model of an atrial myocyte. At the single-cell level, upregulation of the L-type Ca2+ current I(Ca,L) steepened restitution curves of action potential duration and conduction velocity compared with the control. Spontaneous firings of ectopic foci, coupled with sinus activity, produced dynamic spatial dispersions of repolarization, including discordant alternans, which caused conduction block and reentry only for the elevated I(Ca,L) case. For each foci location, a vulnerable window for atrial flutter/atrial fibrillation induction was identified as a function of the coupling interval and focus cycle length. For ectopic foci in the pulmonary veins and left atrium, the site of conduction block and reentry gradually shifted, as a function of coupling interval, from the right atrium to the interatrial area and finally to the left atrium. The size of the vulnerable window was largest for pulmonary vein foci, becoming markedly smaller for right atrial foci, especially those near the sinoatrial node.
  
  
  CONCLUSIONS
  These findings suggest that a mechanism of dynamically induced repolarization dispersion, especially discordant alternans, underlies the induction of atrial flutter/atrial fibrillation by atrial ectopic foci. The sites and likelihood of reentry induction varied according to ectopic focus location and timing, with the largest vulnerable window corresponding to the pulmonary vein region.
authors.affiliation: Department of Medicine, Division of Cardiology, Weill Medical College of Cornell University, New York, NY 10021, USA. yfgong@hotmail.com
authors.forename: Yunfan
authors.initials: Y
authors.lastname: Gong
authors.forename: Fagen
authors.initials: F
authors.lastname: Xie
authors.forename: Kenneth M
authors.initials: KM
authors.lastname: Stein
authors.forename: Alan
authors.initials: A
authors.lastname: Garfinkel
authors.forename: Calin A
authors.initials: CA
authors.lastname: Culianu
authors.forename: Bruce B
authors.initials: BB
authors.lastname: Lerman
authors.forename: David J
authors.initials: DJ
authors.lastname: Christini
mesh_terms: D001281:Atrial Fibrillation / Q000503:physiopathology*; D001282:Atrial Flutter / Q000503:physiopathology; D018880:Atrial Premature Complexes / Q000503:physiopathology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000187:drug effects / Q000502:physiology; D003198:Computer Simulation; D004562:Electrocardiography; D006325:Heart Atria / Q000503:physiopathology; D006329:Heart Conduction System / Q000187:drug effects / Q000503:physiopathology*; D006801:Humans; D015640:Ion Channel Gating / Q000187:drug effects; D008955:Models, Cardiovascular; D011667:Pulmonary Veins
chemical_list: D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type