title: Mechanism of procainamide-induced prevention of spontaneous wave break during ventricular fibrillation. Insight into the maintenance of fibrillation wave fronts.
abstract: BACKGROUND
  Ventricular fibrillation (VF) is maintained by 2 mechanisms: first by reentry formation and second by spontaneous wave break or wave splitting. We hypothesized that spontaneous wave break results from a critical shortening of the action potential duration (APD) during VF and that its prevention by procainamide eliminates spontaneous wave break.
  
  
  RESULTS
  The endocardial surfaces of 7 isolated, perfused swine right ventricles were mapped with a 3.2x3.8 cm plaque with 477 bipolar electrodes. Activation pattern during VF was visualized dynamically while simultaneously recording epicardial action potentials with a glass microelectrode. APD restitution curves were constructed during VF (dynamic) and during S(1)S(2) protocols. At baseline, VF was maintained by 5.3+/-1 wavelets. Procainamide (PA) at 10 microgram/mL decreased the number of wavelets to 3.5+/-1 (P<0.05). At baseline VF was maintained by spontaneous wave break and by new reentrant wave front formation. PA eliminated spontaneous wave break during VF while having no effect on reentry formation. PA increased the cycle length of the VF (148.5+/-41.2 ms vs 81+/-10 ms, P<0.01) and the core area of the reentry from 5.8 to 14.5 mm(2) (P<0.05). Dynamic APD restitution curve during VF showed that PA eliminated the initiation of activation with APDs shorter than 30 ms. The effects of PA on cellular properties and wave front dynamics were reversed during 60 minutes of drug-free perfusion.
  
  
  CONCLUSIONS
  Critically short APDs during VF promote spontaneous wave break. Their elimination with PA, however, maintains VF by generating new reentrant wave front.
authors.affiliation: Divisions of Cardiology, Department of Medicine, Cedars-Sinai Medical Center and UCLA School of Medicine, Los Angeles, Calif, USA.
authors.forename: Y H
authors.initials: YH
authors.lastname: Kim
authors.forename: M
authors.initials: M
authors.lastname: Yashima
authors.forename: T J
authors.initials: TJ
authors.lastname: Wu
authors.forename: R
authors.initials: R
authors.lastname: Doshi
authors.forename: P S
authors.initials: PS
authors.lastname: Chen
authors.forename: H S
authors.initials: HS
authors.lastname: Karagueuzian
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002304:Cardiac Pacing, Artificial; D004562:Electrocardiography; D005260:Female; D006329:Heart Conduction System / Q000187:drug effects* / Q000503:physiopathology; D006352:Heart Ventricles / Q000503:physiopathology; D007552:Isotonic Solutions / Q000494:pharmacology; D008297:Male; D011342:Procainamide / Q000494:pharmacology* / Q000627:therapeutic use; D013552:Swine; D017180:Tachycardia, Ventricular / Q000188:drug therapy / Q000503:physiopathology; D014693:Ventricular Fibrillation / Q000188:drug therapy* / Q000503:physiopathology
chemical_list: D000889:Anti-Arrhythmia Agents; D007552:Isotonic Solutions; C037692:Tyrode's solution; D011342:Procainamide