title: Spatial dispersion of repolarization is a key factor in the arrhythmogenicity of long QT syndrome.
abstract: BACKGROUND
  The occurrence of significant spatial dispersion of repolarization in vivo as it relates to the mechanism of arrhythmia formation in the long QT syndrome (LQTS) continues to be questioned.
  
  
  RESULTS
  We investigated a guinea pig model of LQT3 using anthopleurin-A (AP-A) to study the contribution of rate-dependent spatial dispersion of repolarization in the intact heart to the arrhythmogenicity of LQTS. Optical action potentials were measured using potentiometric fluorescent dye di-4ANEPPS in Langendorff-perfused hearts with induced AV block. AP-A exacerbated the normal uniform epicardial apex-base action potential duration (APD) gradient, resulting in rate-dependent increased APD dispersion and nonuniform APD gradient. Spontaneous focal premature beats induced functional conduction block along boundaries where large nonuniform APD gradient occurred setting the stage for circulating wavefronts and ventricular tachyarrhythmia (VT). Endocardial ablation abolished spontaneous VT, but nonuniform epicardial APD gradient persisted and could be challenged by a stimulated premature stimulus to induce VT.
  
  
  CONCLUSIONS
  The study shows that in LQT3, spatial variations in steady-state properties result in zones of nonuniform APD gradients. These provide a substrate for functional conduction block and reentrant excitation when challenged by subendocardial "early afterdepolarization-triggered" premature beats. The study emphasizes the key importance of spatial dispersion of repolarization, whether located in epicardial or intramyocardial layers, in arrhythmia formation in LQTS.
authors.affiliation: SUNY Downstate Medical Center and VA New York Harbor Healthcare System, Brooklyn, New York 11203, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Restivo
authors.forename: Edward B
authors.initials: EB
authors.lastname: Caref
authors.forename: Dmitry O
authors.initials: DO
authors.lastname: Kozhevnikov
authors.forename: Nabil
authors.initials: N
authors.lastname: El-Sherif
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D018780:Body Surface Potential Mapping; D002316:Cardiotonic Agents / Q000494:pharmacology; D004195:Disease Models, Animal; D004558:Electric Stimulation; D005260:Female; D006168:Guinea Pigs; D006329:Heart Conduction System / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D006346:Heart Septum / Q000503:physiopathology; D006352:Heart Ventricles / Q000503:physiopathology; D036341:Intercellular Signaling Peptides and Proteins; D008133:Long QT Syndrome / Q000503:physiopathology*; D008297:Male; D008955:Models, Cardiovascular; D010455:Peptides / Q000494:pharmacology; D010496:Pericardium / Q000503:physiopathology; D012307:Risk Factors
chemical_list: D002316:Cardiotonic Agents; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; C012746:anthopleurin-A