title: Slow adaptation of ventricular repolarization as a cause of arrhythmia?
abstract: BACKGROUND
  This article is part of the Focus Theme of Methods of Information in Medicine on "Biosignal Interpretation: Advanced Methods for Studying Cardiovascular and Respiratory Systems".
  
  
  BACKGROUND
  Adaptation of the QT-interval to changes in heart rate reflects on the body-surface electrocardiogram the adaptation of action potential duration (APD) at the cellular level. The initial fast phase of APD adaptation has been shown to modulate the arrhythmia substrate. Whether the slow phase is potentially proarrhythmic remains unclear.
  
  
  OBJECTIVE
  To analyze in-vivo human data and use computer simulations to examine effects of the slow APD adaptation phase on dispersion of repolarization and reentry in the human ventricle.
  
  
  METHODS
  Electrograms were acquired from 10 left and 10 right ventricle (LV/RV) endocardial sites in 15 patients with normal ventricles during RV pacing. Activation-recovery intervals, as a surrogate for APD, were measured during a sustained increase in heart rate. Observed dynamics were studied using computer simulations of human tissue electrophysiology.
  
  
  RESULTS
  Spatial heterogeneity of rate adaptation was observed in all patients. Inhomogeneity in slow APD adaptation time constants (Δτ(s)) was greater in LV than RV (Δτ(s)(LV) = 31.8 ± 13.2, Δτ(s)(RV) = 19.0 ± 12.8 s , P< 0.01). Simulations showed that altering local slow time constants of adaptation was sufficient to convert partial wavefront block to block with successful reentry.
  
  
  CONCLUSIONS
  Using electrophysiological data acquired in-vivo in human and computer simulations, we identify heterogeneity in the slow phase of APD adaptation as an important component of arrhythmogenesis.
authors.affiliation: Alfonso Bueno-Orovio, Department of Computer Science, University of Oxford, Wolfson Building, Parks Road, Oxford, OX1 3QD, United Kingdom, E-mail: alfonso.bueno@cs.ox.ac.uk.
authors.forename: A
authors.initials: A
authors.lastname: Bueno-Orovio
authors.forename: B M
authors.initials: BM
authors.lastname: Hanson
authors.forename: J S
authors.initials: JS
authors.lastname: Gill
authors.forename: P
authors.initials: P
authors.lastname: Taggart
authors.forename: B
authors.initials: B
authors.lastname: Rodriguez
mesh_terms: D000328:Adult; D000368:Aged; D001145:Arrhythmias, Cardiac / Q000503:physiopathology*; D001281:Atrial Fibrillation / Q000503:physiopathology*; D003198:Computer Simulation; D004562:Electrocardiography; D004699:Endocardium / Q000503:physiopathology*; D005260:Female; D005583:Fourier Analysis; D006325:Heart Atria / Q000503:physiopathology; D006352:Heart Ventricles / Q000503:physiopathology*; D006801:Humans; D008875:Middle Aged; D010496:Pericardium / Q000503:physiopathology*; D012815:Signal Processing, Computer-Assisted; D013611:Tachycardia, Atrioventricular Nodal Reentry / Q000503:physiopathology; D056969:Voltage-Sensitive Dye Imaging
keywords: Cardiac arrhythmias; reentry; repolarization and QT interval