title: Drug-induced narrowing of the width of the zone of entrainment as a predictor of the subsequent non-inducibility of reentrant ventricular tachycardia after an additional dose of an antiarrhythmic drug.
abstract: BACKGROUND
  The efficacy of drugs used to treat inducible monomorphic sustained ventricular tachycardia (VT) has been assessed by investigating their ability to suppress inducibility, but the mechanism of the drug action remains to be determined.
  
  
  OBJECTIVE
  To determine electrophysiological variables that predict inducibility, divided doses of class I antiarrhythmic drugs were given and their effects were analysed, particularly the ability of the final dose to suppress inducibility.
  
  
  METHODS
  The excitable gap was estimated by the zone of entrainment, which was defined as the difference between the cycle length of VT and the longest paced cycle length that interrupted VT during entrainment of VT with rapid pacing at paced cycle lengths in decrements of 10 ms. The cycle length of VT, the block cycle length, and the zone of entrainment were measured in the drug free state and after intermediate and final doses of procainamide, disopyramide, cibenzoline, and mexiletine.
  
  
  RESULTS
  Sustained monomorphic VT with a mean (SD) cycle length of 285 (43) ms was induced in 8 patients. It was entrained and interrupted at the block cycle length of 231 (31) ms. The width of the zone of entrainment was 54 (23) ms. In 8 studies VT was not inducible at final doses of procainamide in 4, cibenzoline in 1, and mexiletine in 3. In another 10 studies (procainamide in 4, disopyramide in 1, cibenzoline in 2, and mexiletine in 3), VT remained inducible at the intermediate dose and at the final dose. The cycle length of VT was prolonged to a similar degree in studies of effective and ineffective drugs, but the cycle length that blocked VT was longer at the intermediate dose of the effective drugs. Consequently, the width of the zone of entrainment was significantly narrowed at the intermediate dose of effective drugs and the width of the zone of entrainment was narrower than when ineffective drugs were given (22 (13) ms v 76 (18) or 75 (37) ms at the intermediate and final doses respectively (P < 0.02).
  
  
  CONCLUSIONS
  Drugs that narrowed the zone of entrainment were associated with non-inducibility of VT after the final dose of the drug was given. The baseline variables did not predict the responses to class I antiarrhythmic drugs.
authors.affiliation: First Department of Internal Medicine, Niigata University School of Medicine, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Aizawa
authors.forename: M
authors.initials: M
authors.lastname: Chinushi
authors.forename: N
authors.initials: N
authors.lastname: Naitoh
authors.forename: A
authors.initials: A
authors.lastname: Shibata
mesh_terms: D000328:Adult; D000368:Aged; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D002304:Cardiac Pacing, Artificial; D004206:Disopyramide / Q000008:administration & dosage / Q000627:therapeutic use; D004334:Drug Administration Schedule; D004562:Electrocardiography / Q000187:drug effects*; D005260:Female; D006321:Heart / Q000187:drug effects; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage / Q000627:therapeutic use; D008297:Male; D008801:Mexiletine / Q000008:administration & dosage / Q000627:therapeutic use; D008875:Middle Aged; D011342:Procainamide / Q000008:administration & dosage / Q000627:therapeutic use; D017180:Tachycardia, Ventricular / Q000188:drug therapy / Q000503:physiopathology*
chemical_list: D000889:Anti-Arrhythmia Agents; D007093:Imidazoles; D008801:Mexiletine; D004206:Disopyramide; D011342:Procainamide; C032151:cifenline