title: Transmural dispersion of repolarization determines scroll wave behavior during ventricular tachyarrhythmias.
abstract: BACKGROUND
  Ventricular tachyarrhythmia is the leading cause of sudden cardiac death, and scroll wave re-entry is known to underlie this condition. Class III antiarrhythmic drugs are commonly used worldwide to treat ventricular tachyarrhythmias; however, these drugs have a proarrhythmic adverse effect and can cause Torsade de Pointes or ventricular fibrillation. Transmural dispersion of repolarization (TDR) has been suggested to be a strong indicator of ventricular tachyarrhythmia induction. However, the role of TDR during sustained scroll wave re-entry is poorly understood. The purpose of the present study was to investigate how TDR affects scroll wave behavior and to provide a novel analysis of the mechanisms that sustain tachyarrhythmias, using computer simulations.
  
  
  RESULTS
  Computer simulations were carried out to quantify the TDR and QT interval under a variety of I(Ks) and I(Kr) during transmural conduction. Simulated scroll wave re-entries were done under a variety of I(Ks) and I(Kr) in a ventricular wall slab model, and the scroll wave behavior and the filament dynamics (3-dimensional organizing center) were analyzed. A slight increase in TDR, but not in the QT interval, reflected antiarrhythmic properties resulting from the restraint of scroll wave breakup, whereas a marked increase in TDR was proarrhythmic, as a result of scroll wave breakup.
  
  
  CONCLUSIONS
  The TDR determines the sustainment of ventricular tachyarrhythmias, through control of the scroll wave filament dynamics.
authors.affiliation: National Cerebral and Cardiovascular Center Research Institute, Suita, Japan. haraguch@ri.ncvc.go.jp
authors.forename: Ryo
authors.initials: R
authors.lastname: Haraguchi
authors.forename: Takashi
authors.initials: T
authors.lastname: Ashihara
authors.forename: Tsunetoyo
authors.initials: T
authors.lastname: Namba
authors.forename: Kunichika
authors.initials: K
authors.lastname: Tsumoto
authors.forename: Shingo
authors.initials: S
authors.lastname: Murakami
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Kurachi
authors.forename: Takanori
authors.initials: T
authors.lastname: Ikeda
authors.forename: Kazuo
authors.initials: K
authors.lastname: Nakazawa
mesh_terms: D000200:Action Potentials; D000889:Anti-Arrhythmia Agents / Q000009:adverse effects; D003198:Computer Simulation; D006329:Heart Conduction System / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D006352:Heart Ventricles / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D006801:Humans; D021621:Imaging, Three-Dimensional; D007700:Kinetics; D008955:Models, Cardiovascular; D032383:Myocytes, Cardiac / Q000378:metabolism; D011188:Potassium / Q000378:metabolism; D015221:Potassium Channels / Q000378:metabolism; D017180:Tachycardia, Ventricular / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology*; D016171:Torsades de Pointes / Q000209:etiology / Q000503:physiopathology; D014693:Ventricular Fibrillation / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology*
chemical_list: D000889:Anti-Arrhythmia Agents; D015221:Potassium Channels; D011188:Potassium