title: Combination therapy with mexiletine and sotalol suppresses inherited ventricular arrhythmias in German shepherd dogs better than mexiletine or sotalol monotherapy: a randomized cross-over study.
abstract: OBJECTIVE
  To determine the spontaneous variability of ventricular arrhythmias (VA) and evaluate anti-arrhythmic efficacy of mexiletine, sotalol, and a mexiletine-sotalol combination in German shepherd dogs (GSD) with inherited arrhythmias.
  
  
  METHODS
  12 affected GSD, median age 20 weeks, received mexiletine (8 mg/kg PO q8 h), sotalol (2.5 mg/kg PO q12 h), and combination therapy for 6 days in random order. Pre- and post-treatment 24 h Holter recordings were acquired, allowing determination of VA variability and reduction in 24 h VA for each treatment. Drug concentrations during each arm were measured.
  
  
  RESULTS
  An anti-arrhythmic effect could be inferred if ventricular premature complexes (VPC), ventricular couplets (V(cpl)), ventricular tachycardia runs (VT(runs)) and total ventricular ectopy (VE(tot)) frequency were reduced by 61%, 97%, 98%, and 63% (1 control Holter model), by 53%, 94%, 95%, and 54% (4 control Holter model) and by 54%, 95%, 96% and 56% (3 control Holter model). Combination therapy reduced VPC and VE(tot) in more dogs (5/12 and 6/12) than mexiletine (1/11 and 2/11) or sotalol (2/9 and 1/9) (p < 0.05). The combination therapy reduced the mean number of VPC, V(cpl), and VE(tot). Sotalol monotherapy produced an increase in VT(runs). Plasma mexiletine concentration was higher during combination therapy than with monotherapy.
  
  
  CONCLUSIONS
  Combination therapy reduced VPC in affected GSD. Sotalol monotherapy increased VT(runs). Combination therapy increased plasma mexiletine concentrations.
authors.affiliation: Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA. arg9@cornell.edu
authors.forename: Anna R M
authors.initials: AR
authors.lastname: Gelzer
authors.forename: Marc S
authors.initials: MS
authors.lastname: Kraus
authors.forename: Mark
authors.initials: M
authors.lastname: Rishniw
authors.forename: Shari A
authors.initials: SA
authors.lastname: Hemsley
authors.forename: N Sydney
authors.initials: NS
authors.lastname: Moïse
mesh_terms: D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D001145:Arrhythmias, Cardiac / Q000188:drug therapy / Q000662:veterinary*; D018592:Cross-Over Studies; D004283:Dog Diseases / Q000188:drug therapy*; D004285:Dogs; D004359:Drug Therapy, Combination / Q000662:veterinary; D015716:Electrocardiography, Ambulatory / Q000662:veterinary; D005260:Female; D008297:Male; D008801:Mexiletine / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D011446:Prospective Studies; D013015:Sotalol / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D017180:Tachycardia, Ventricular / Q000188:drug therapy / Q000662:veterinary; D018879:Ventricular Premature Complexes / Q000188:drug therapy / Q000662:veterinary
chemical_list: D000889:Anti-Arrhythmia Agents; D008801:Mexiletine; D013015:Sotalol