title: Transseptal dispersion of repolarization and its role in the development of Torsade de Pointes arrhythmias.
abstract: OBJECTIVE
  This study was designed to quantitate transseptal dispersion of repolarization (DR) and delineate its role in arrhythmogenesis using the calcium agonist BayK 8644 to mimic the gain of function of calcium channel current responsible for Timothy syndrome.
  
  
  BACKGROUND
  Amplification of transmural dispersion of repolarization (TDR) has been shown to contribute to development of Torsade de Pointes (TdP) arrhythmias under long-QT conditions.
  
  
  METHODS
  An arterially perfused septal wedge preparation was developed via cannulation of the septal artery. Action potentials (APs) were recorded using floating microelectrodes together with a transseptal electrocardiogram (ECG). These data were compared to those recorded from arterially perfused canine left ventricular (LV) wedge preparations.
  
  
  RESULTS
  Under control conditions, the shortest AP duration measured at 90% repolarization (APD(90)) was observed in right ventricular (RV) endocardium (181.8 +/- 15 ms), APD(90) peaked close to midseptum (278.0 +/- 32 ms), and abbreviated again as LV endocardium was approached (207.3 +/- 9 ms). Transseptal DR averaged 106 +/- 24 ms and T(peak)-T(end) 84 +/- 7 ms (n = 6). TDR and T(peak)-T(end) recorded from LV wedge were 36 +/- 9 ms and 34 +/- 19 ms, respectively (n = 30). BayK 8644 increased transseptal DR to 123.2 +/- 35 ms (n = 5) and induced early and delayed afterdepolarizations (3/5), rate-dependent ST-T-wave alternans (5/5), and TdP arrhythmias (3/5).
  
  
  CONCLUSIONS
  Our data indicate that dispersion of repolarization across the interventricular septum is twice that of the LV free wall, predisposing to development of TdP under long-QT conditions. Our findings suggest that the coronary-perfused ventricular septal preparation may be a sensitive model in which to assess the potential arrhythmogenic effects of drugs and pathophysiological conditions.
authors.affiliation: Masonic Medical Research Laboratory, Utica, New York 13501, USA. sicouris@mmrl.edu
authors.forename: Serge
authors.initials: S
authors.lastname: Sicouri
authors.forename: Aaron
authors.initials: A
authors.lastname: Glass
authors.forename: Marcela
authors.initials: M
authors.lastname: Ferreiro
authors.forename: Charles
authors.initials: C
authors.lastname: Antzelevitch
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004285:Dogs; D006329:Heart Conduction System / Q000503:physiopathology*; D006346:Heart Septum / Q000503:physiopathology*; D006801:Humans; D016171:Torsades de Pointes / Q000503:physiopathology*