title: Effects of flecainide, encainide, and clofilium on ventricular refractory period extension by transcardiac shocks.
abstract: OBJECTIVE
  The mechanisms by which pharmacological agents alter electrical defibrillation are not fully understood. It has been proposed that, in addition to directly stimulating tissue, defibrillation may involve refractory period extension (RPE) produced by the shock. Accordingly, pharmacological agents might modulate defibrillation by altering RPE. This study examined the effect of Class I and Class III antiarrhythmic agents on RPE by transcardiac shocks.
  
  
  METHODS
  In four groups of pentobarbital anesthetized dogs, RPE was measured during rapid ventricular pacing before and after administration of either the Class I agents flecainide (n = 7) or encainide (n = 7), the Class III agent clofilium (n = 7), or vehicle (n = 5). Measurements included QRS duration during sinus rhythm and a conduction time, QTC interval and refractory period, and RPE for 4- to 10-V/cm shocks delivered 20-80 ms before the end of the tissue absolute refractory period. For the 6-V/cm shocks, the interval after the shock during which tissue remained refractory (RIAS) was also computed.
  
  
  RESULTS
  Drugs affected QRS duration, conduction time, QTC, and refractory period ( without shocks) in accordance with their anticipated Class I and Class III actions. Without drugs, significant RPE was observed in all animals for all shocks delivered 40 ms or less before the end of the refractory period. Clofilium, encainide, and flecainide had a tendency to increase RPE but only clofilium produced a significant increase. For 6-V/cm shocks with different timings, the minimum RIAS was found to be approximately 43 ms, and occurred for shocks given 20-30 ms before the end of the refractory period.
  
  
  CONCLUSIONS
  At drug dosages that produced moderate Class III ( approximately equal to 15%) or strong Class I (approximately equal to 35%) effects, only the Class III agent significantly increased RPE and RIAS. Thus, in addition to altering tissue excitability, the effect of antiarrhythmic agents to increase RPE and the minimum RIAS may help explain their influence on defibrillation threshold.
authors.affiliation: Department of Electrophysiology Research, Lilly Research Laboratories Division, Eli Lilly and Company, Indianapolis, Indiana, USA.
authors.forename: R J
authors.initials: RJ
authors.lastname: Sweeney
authors.forename: R M
authors.initials: RM
authors.lastname: Gill
authors.forename: M I
authors.initials: MI
authors.lastname: Steinberg
authors.forename: P R
authors.initials: PR
authors.lastname: Reid
mesh_terms: D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D002304:Cardiac Pacing, Artificial; D004285:Dogs; D004554:Electric Countershock; D016700:Encainide / Q000494:pharmacology; D005424:Flecainide / Q000494:pharmacology; D006329:Heart Conduction System / Q000187:drug effects* / Q000502:physiology; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology; D012032:Refractory Period, Electrophysiological / Q000187:drug effects; D013997:Time Factors; D014693:Ventricular Fibrillation / Q000503:physiopathology / Q000628:therapy*; D016276:Ventricular Function / Q000187:drug effects* / Q000502:physiology
chemical_list: D000889:Anti-Arrhythmia Agents; D000644:Quaternary Ammonium Compounds; C022799:clofilium; D005424:Flecainide; D016700:Encainide