title: Prevention of ventricular extrasystole by mexiletine in patients with normal QT intervals is associated with a reduction of transmural dispersion of repolarization.
abstract: BACKGROUND
  Antiarrhythmic potential of mexiletine in patients with congenital and acquired long-QT syndrome (LQTS) has been attributed to a reduction of transmural dispersion of repolarization (TDR). A similar mechanism could be involved in the antiarrhythmic activity of the drug in patients with normal QT intervals, but the issue remains to be investigated.
  
  
  RESULTS
  We analyzed 24-h Holter ECG recordings from 17 patients in sinus rhythm showing premature ventricular complexes (PVCs) with normal QT intervals (age, 62+/-10 years, mean+/-S.D.). Treatment of the patients with oral mexiletine (300 mg/day for 21-40 days) resulted in a significant reduction of PVCs (from 13899+/-18887 to 6949+/-12822 beats/24 h, p<0.01). Rate-dependent behavior of ventricular repolarization was analyzed by plotting QT intervals (QT(peak), QT(end)), and the interval from T-wave peak to T-wave end (TPE) against preceding respective RR intervals of sinus beats. Both the QT(peak) and QT(end) tended to be shortened by mexiletine at RR intervals from 600 ms to 1000 ms, although the changes did not reach statistical significances. TPE, which reflects TDR, was shortened significantly at relatively long RR intervals (by 14+/-9% at RR of 900 ms, p<0.05). There was a linear relationship between the percentage shortening of TPE and the percentage reduction of PVCs (r=0.86, p<0.04). TPE> or =70 ms was significantly associated with PVC suppression >75% with an odds ratio of 0.60 (95% confidence interval 0.36-0.98, per 1 ms increment).
  
  
  CONCLUSIONS
  Inhibitory effect of mexiletine against PVCs in patients with normal QT intervals is mediated at least in part by a reduction of TDR. Mexiletine may be effective in patients exhibiting longer baseline TPE.
authors.affiliation: Department of Cardiology, Gifu Shakai Hoken Hospital, Kani, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Yamauchi
authors.forename: Eiichi
authors.initials: E
authors.lastname: Watanabe
authors.forename: Kenji
authors.initials: K
authors.lastname: Yasui
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Takeuchi
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Terasawa
authors.forename: Ken
authors.initials: K
authors.lastname: Sawada
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Hishida
authors.forename: Itsuo
authors.initials: I
authors.lastname: Kodama
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000284:Administration, Oral; D000368:Aged; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D015716:Electrocardiography, Ambulatory; D005260:Female; D005500:Follow-Up Studies; D006329:Heart Conduction System / Q000187:drug effects / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D008297:Male; D008801:Mexiletine / Q000008:administration & dosage / Q000627:therapeutic use*; D008875:Middle Aged; D016896:Treatment Outcome; D018879:Ventricular Premature Complexes / Q000503:physiopathology / Q000517:prevention & control*
chemical_list: D000889:Anti-Arrhythmia Agents; D008801:Mexiletine