title: Epicardial but not endocardial premature stimulation initiates ventricular tachyarrhythmia in canine in vitro model of long QT syndrome.
abstract: OBJECTIVE
  To explore the mechanism, we tested the hypothesis that premature epicardial stimulation transiently increased the dispersion of repolarization leading to VT.
  
  
  BACKGROUND
  Premature stimulation initiated ventricular tachycardia (VT) when applied to the epicardium but not to the endocardium in a canine model of long QT syndrome (LOTS).
  
  
  METHODS
  We optically mapped action potentials (APs) on the cut-exposed transmural surfaces of isolated wedges of canine ventricular walls perfused with anemone toxin II (ATX-II), which produced type 3 LQTS with an asymmetrical transmural profile of repolarization that was earliest in the epicardium and latest in deep subendocardium.
  
  
  RESULTS
  Earliest excitable epicardial stimulation triggered VT in 5 of 18 wedges receiving > or =5 nmol/L ATX-II by direct activation of epicardium, which delayed repolarization in the still refractory midmyocardium and further enhanced the dispersion of repolarization. These VTs were initiated 197 +/- 72 ms (n = 10) after the premature stimulation, from focal regions of earliest repolarization downstream to the steepest local spatial gradients of repolarization, and maintained by new focal activation and reentry. Transmural differences in the cycle lengths of activations altered conduction pathways and resulted in torsades de pointes-like polymorphic VT. In contrast, VTs were not initiated by endocardial stimulation at the same premature intervals or when ATX-II was < or =2.5 nmol/L. Failed VT initiation was associated with significantly lower maximum local gradient of repolarization.
  
  
  CONCLUSIONS
  Heterogeneic repolarization in LQTS provides a transmural asymmetrical substrate for the earliest excitable epicardial, but not endocardial, stimulation to further delay midmyocardial repolarization and produce a steep spatial gradient of repolarization potential initiating torsades de pointes-like polymorphic VT.
authors.affiliation: Krannert Institute of Cardiology, Indiana University School of Medicine, Indianapolis, 46202, USA.
authors.forename: Norihiro
authors.initials: N
authors.lastname: Ueda
authors.forename: Douglas P
authors.initials: DP
authors.lastname: Zipes
authors.forename: Jiashin
authors.initials: J
authors.lastname: Wu
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology; D003064:Cnidarian Venoms / Q000494:pharmacology; D004285:Dogs; D004558:Electric Stimulation; D004699:Endocardium / Q000503:physiopathology*; D066298:In Vitro Techniques; D008133:Long QT Syndrome / Q000139:chemically induced / Q000503:physiopathology*; D023421:Models, Animal; D010477:Perfusion; D010496:Pericardium / Q000503:physiopathology*; D017180:Tachycardia, Ventricular / Q000209:etiology* / Q000503:physiopathology
chemical_list: D002316:Cardiotonic Agents; D003064:Cnidarian Venoms; C028800:toxin II (Anemonia sulcata)