title: Preferential action of mexiletine on central common pathway of reentrant ventricular tachycardia.
abstract: OBJECTIVE
  The action of mexiletine on diseased myocardium was assessed in reentrant ventricular tachycardia (VT).
  
  
  BACKGROUND
  Whether class Ib antiarrhythmic agents exert a preferential action on the central common pathway of reentrant ventricular tachycardia has not yet been studied in humans.
  
  
  METHODS
  In 10 consecutive patients (7 with a previous myocardial infarction, 3 with nonischemic disease), VT was induced and entrained with rapid pacing. The orthodromic conduction time was measured from stimulus to the entrained electrogram at the exit from the presumed central common pathway (i.e., the earliest site of activation). Mexiletine at 125 to 250 mg was administered intravenously, and when VT with the same configuration was induced, the study was repeated. The action of mexiletine on the central common pathway was assessed from the changes in VT cycle length and orthodromic conduction time. The effects on QRS complex duration, local conduction time between the exit and the pacing site and duration of the local electrogram were compared between normal and diseased myocardium.
  
  
  RESULTS
  Mexiletine prolonged the VT cycle length in all patients, from (mean +/- SD) 316 +/- 30 to 360 +/- 64 ms (mean change 20 +/- 7%, p < 0.001); during entrainment of VT, the orthodromic conduction time was prolonged, from 306 +/- 58 to 367 +/- 89 ms (mean change 18 +/- 9%, p < 0.001). These changes were highly correlated (r = 0.95, p < 0.001). QRS duration changed little (4 +/- 3%), and local conduction time showed no change. The duration of the fragmented electrogram width was prolonged by mexiletine: from 146 +/- 50 to 176 +/- 56 ms (mean change 23 +/- 8% during VT, p < 0.001). Only a slight change occurred in the effective refractory period, both at the pacing site and at the exit.
  
  
  CONCLUSIONS
  Mexiletine caused little change in conduction time in normal myocardium but prolonged VT cycle length, orthodromic conduction time and duration of the local electrogram at the earliest site of activation of VT. From these findings, a preferential action of mexiletine on diseased myocardium was suggested but seemed to occur only at higher frequencies during tachycardia.
authors.affiliation: First Department of Internal Medicine, Niigata University School of Medicine, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Aizawa
authors.forename: A
authors.initials: A
authors.lastname: Abe
authors.forename: K
authors.initials: K
authors.lastname: Ohira
authors.forename: H
authors.initials: H
authors.lastname: Furushima
authors.forename: M
authors.initials: M
authors.lastname: Chinushi
authors.forename: S
authors.initials: S
authors.lastname: Fujita
mesh_terms: D000328:Adult; D000368:Aged; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D002304:Cardiac Pacing, Artificial; D004562:Electrocardiography; D005260:Female; D006329:Heart Conduction System / Q000187:drug effects* / Q000503:physiopathology; D006801:Humans; D008297:Male; D008801:Mexiletine / Q000494:pharmacology*; D008875:Middle Aged; D017180:Tachycardia, Ventricular / Q000503:physiopathology*
chemical_list: D000889:Anti-Arrhythmia Agents; D008801:Mexiletine