title: Refractory gradient is responsible for the increase in ventricular vulnerability under sodium channel blockade.
abstract: BACKGROUND
  Previous studies have shown that sodium channel (I(Na)) blockade increases ventricular vulnerability; however, there were differences in the degree of the increase. Because the vulnerable window (VW) is altered by the type of preshock refractory gradient (RG), the hypothesis was that the differences in the arrhythmogenesis of I(Na) blockade result from the different types of preshock RG employed.
  
  
  RESULTS
  Simulations of regio(Na)l electric shock following constant pacing stimuli in 2-dimensional bidomain myocardial sheets under I(Na) blockade were conducted using 3 types of preshock RG: longitudinally tilted (LRG), transversely tilted (TRG), and non-tilted RG (NRG). The increase in the degree of I(Na) blockade almost linearly decreased the conduction velocity. The action potential duration in the LRG and TRG cases was non-linearly shortened with the increase in INa blockade because of electrotonic influences, whereas in the case of NRG it was slightly prolonged. In both LRG and TRG cases, the VW for reentry induction by electric shock was considerably widened by the INa blockade; however, this was not the case for NRG in which the VW was rather narrowed by the INa blockade.
  
  
  CONCLUSIONS
  The type of preshock RG alters the degree of the increase in ventricular vulnerability under INa blockade.
authors.affiliation: Department of Cardiovascular and Respiratory Medicine, Shiga University of Medical Science, Osu, Japan. yao@voyage.shiga-med.ac.jp
authors.forename: Takenori
authors.initials: T
authors.lastname: Yao
authors.forename: Takashi
authors.initials: T
authors.lastname: Ashihara
authors.forename: Makoto
authors.initials: M
authors.lastname: Ito
authors.forename: Kazuo
authors.initials: K
authors.lastname: Nakazawa
authors.forename: Minoru
authors.initials: M
authors.lastname: Horie
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D002304:Cardiac Pacing, Artificial; D017147:Defibrillators, Implantable; D004553:Electric Conductivity; D004558:Electric Stimulation; D006352:Heart Ventricles / Q000187:drug effects; D006801:Humans; D008564:Membrane Potentials / Q000187:drug effects; D008955:Models, Cardiovascular; D026941:Sodium Channel Blockers / Q000494:pharmacology*; D016276:Ventricular Function
chemical_list: D026941:Sodium Channel Blockers