title: Widening of the excitable gap and enlargement of the core of reentry during atrial fibrillation with a pure sodium channel blocker in canine atria.
abstract: BACKGROUND
  This study aimed to assess the effects of pilsicainide, a pure sodium channel blocker, on electrophysiological action and wavefront dynamics during atrial fibrillation (AF).
  
  
  RESULTS
  In a newly developed model of isolated, perfused, and superfused canine atria (n=12), the right and left endocardia were mapped simultaneously by use of a computerized mapping system. AF was induced with 1 to 5 micromol/L acetylcholine. The antifibrillatory actions of pilsicainide on AF cycle length (AFCL), refractory period (RP), conduction velocity (CV), excitable gap (EG), and the core of the mother rotor were studied. The RP was defined as the shortest coupling interval that could capture the fibrillating atrium. The EG was estimated as the difference between the AFCL and RP. At baseline, multiple wavefronts were observed. After 2.5 microg/mL infusion of pilsicainide, all preparations showed irregular activity, and AF was terminated in 2 preparations. The AFCL and RP were prolonged, and CV was decreased significantly. The EG was widened (147%; P<0.01), and the core perimeter was increased (100%; P<0.01). Increasing the dosage either terminated AF (6 preparations) or converted to organized activity (ie, atypical atrial flutter) (4 preparations). On the maps, all "unorganized" AFs were terminated with the excitation of the core of the mother rotor by an outside wavefront, whereas in preparations with atrial flutter, pilsicainide did not terminate its activity.
  
  
  CONCLUSIONS
  Widening of the EG by pilsicainide facilitates the excitation of the core of the mother rotor, leading to the termination of AF. In some experiments, pilsicainide converts AF to persistent atrial flutter.
authors.affiliation: Third Department of Internal Medicine, Toho University School of Medicine, Tokyo, Japan.
authors.forename: Ayaka
authors.initials: A
authors.lastname: Kawase
authors.forename: Takanori
authors.initials: T
authors.lastname: Ikeda
authors.forename: Kazuo
authors.initials: K
authors.lastname: Nakazawa
authors.forename: Takashi
authors.initials: T
authors.lastname: Ashihara
authors.forename: Tsunetoyo
authors.initials: T
authors.lastname: Namba
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Kubota
authors.forename: Kaoru
authors.initials: K
authors.lastname: Sugi
authors.forename: Hironori
authors.initials: H
authors.lastname: Hirai
mesh_terms: D000109:Acetylcholine; D000818:Animals; D001281:Atrial Fibrillation / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology*; D018780:Body Surface Potential Mapping; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography; D022062:Electrophysiologic Techniques, Cardiac; D005260:Female; D006325:Heart Atria / Q000187:drug effects* / Q000503:physiopathology*; D066298:In Vitro Techniques; D008012:Lidocaine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D026941:Sodium Channel Blockers / Q000494:pharmacology*
chemical_list: D026941:Sodium Channel Blockers; D008012:Lidocaine; C042288:pilsicainide; D000109:Acetylcholine