title: Arrhythmogenesis of T wave alternans associated with surface QRS complex alternans and the role of ventricular prematurity: observations from a canine model of LQT3 syndrome.
abstract: BACKGROUND
  T wave alternans (TWA) is characterized by cycle-to-cycle changes in the QT interval and/or T wave morphology. It is believed to amplify the underlying dispersion of ventricular repolarization. The aim of this study was to examine the mechanisms and arrhythmogenesis of TWA accompanied by QRS complex and/or blood pressure (BP) waveform alternans, using transmural ventricular electrogram recordings in an anthopleurin-A model of long QT syndrome.
  
  
  RESULTS
  The cardiac cycle length was gradually shortened by interruption of vagal stimulation, and TWA was induced in six canine hearts. Transmural unipolar electrograms were recorded with plunge needle electrodes from endocardial (Endo), mid-myocardial (Mid), and epicardial (Epi) sites, along with the surface ECG and BP. The activation-recovery interval (ARI) was measured to estimate local refractoriness. During TWA, ARI alternans was greater at the Mid than the Epi/Endo sites, and it was associated with the development of marked spatial dispersion of ventricular repolarization. As TWA increased, ventricular activation of the cycles associated with shorter QT intervals displayed delayed conduction at the Mid sites as a result of a critically longer ARI of the preceding cycle and longer QT interval, while normal conduction was preserved at the Epi site. Delayed conduction at the Mid sites manifested as surface ECG QRS and BP waveform alternans, and spontaneous ventricular tachyarrhythmias developed in absence of ventricular prematurity. In other instances, in absence of delayed conduction during TWA, ventricular premature complexes infringed on a prominent spatial dispersion of ventricular repolarization of cycles with long QT intervals and initiated ventricular tachyarrhythmia.
  
  
  CONCLUSIONS
  TWA accompanied by QRS alternans may signal a greater ventricular electrical instability, since it is associated with intramural delayed conduction, which can initiate ventricular tachyarrhythmia without ventricular premature complexes.
authors.affiliation: School of Health Science, Niigata University School of Medicine, Japan. masaomi@clg.niigata.u.ac.jp
authors.forename: Masaomi
authors.initials: M
authors.lastname: Chinushi
authors.forename: Yukio
authors.initials: Y
authors.lastname: Hosaka
authors.forename: Takashi
authors.initials: T
authors.lastname: Washizuka
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Furushima
authors.forename: Yoshifusa
authors.initials: Y
authors.lastname: Aizawa
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D002316:Cardiotonic Agents; D004195:Disease Models, Animal; D004285:Dogs; D004562:Electrocardiography; D006329:Heart Conduction System / Q000503:physiopathology; D036341:Intercellular Signaling Peptides and Proteins; D008133:Long QT Syndrome / Q000150:complications / Q000503:physiopathology; D008955:Models, Cardiovascular; D010455:Peptides; D013599:Systole / Q000502:physiology; D017180:Tachycardia, Ventricular / Q000139:chemically induced / Q000503:physiopathology; D016277:Ventricular Function, Left / Q000502:physiology; D018879:Ventricular Premature Complexes / Q000150:complications / Q000503:physiopathology*
chemical_list: D002316:Cardiotonic Agents; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; C012746:anthopleurin-A