title: Divergent effect of acute ventricular dilatation on the electrophysiologic characteristics of d,l-sotalol and flecainide in the isolated rabbit heart.
abstract: BACKGROUND
  The interaction between acute ventricular dilatation (AVD) as one aspect of ventricular dysfunction and Class I and III antiarrhythmic drugs is uncertain. We therefore investigated the effects of AVD on the electrophysiologic properties of d,l-sotalol and flecainide.
  
  
  RESULTS
  The isolated rabbit heart was used as a model of AVD. The ventricular size and, therefore, the diastolic pressure were modified by sudden volume changes of a fluid-filled balloon placed in the left ventricle. Pacing was performed alternately using epi- and endocardial monophasic action potential (MAP)-pacing catheters at cycle lengths from 1,000 to 300 msec. d,l-Sotalol (10 microM) resulted in a significant (P < 0.05) lengthening of refractoriness (+13.5% +/- 3.1%), MAP duration (+14.9% +/- 3.2%), and QT interval (+15.5% +/- 4.1%) (mean +/- SEM at 1,000 msec). These effects had a reverse rate-dependence. AVD to a diastolic pressure of 30 mmHg reduced refractoriness and left ventricular MAP duration. In comparison with the control group with the same extent of AVD, d,l-sotalol still led to a significant prolongation of repolarization for all cycle lengths except 300 msec, so that its effects were not absolutely but relatively preserved. In contrast, flecainide (2 microM) had no significant effects on refractoriness or MAP duration. It led to a significant, rate-dependent increase of pacing thresholds (+47.6% +/- 8.2%), prolongation of QRS (+48.8% +/- 5.6%), and conduction time (+78.6% +/- 8.6%) (mean +/- SEM at 300 msec). In the flecainide group, AVD significantly increased the normal rate-dependent prolongation of QRS (+16.7% +/- 5.5%) and conduction time (+17.1% +/- 4.3%).
  
  
  CONCLUSIONS
  Our data demonstrate that, during AVD, the Class III effect of d,l-sotalol is preserved, whereas flecainide's effect of slowing conduction is exaggerated. This may contribute to flecainide-related proarrhythmia in certain clinical situations.
authors.affiliation: Hospital of the Westfälische Wilhelms-University, Department of Cardiology and Angiology and Institute for Arteriosclerosis Research, Münster, Germany. l.eckardt@uni-muenster.de
authors.forename: L
authors.initials: L
authors.lastname: Eckardt
authors.forename: W
authors.initials: W
authors.lastname: Haverkamp
authors.forename: U
authors.initials: U
authors.lastname: Göttker
authors.forename: M
authors.initials: M
authors.lastname: Madeja
authors.forename: R
authors.initials: R
authors.lastname: Johna
authors.forename: M
authors.initials: M
authors.lastname: Borggrefe
authors.forename: G
authors.initials: G
authors.lastname: Breithardt
mesh_terms: D000200:Action Potentials; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D004108:Dilatation, Pathologic / Q000503:physiopathology; D004562:Electrocardiography; D005424:Flecainide / Q000494:pharmacology*; D006329:Heart Conduction System / Q000187:drug effects / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D011817:Rabbits; D015203:Reproducibility of Results; D013015:Sotalol / Q000494:pharmacology*; D018487:Ventricular Dysfunction, Left / Q000150:complications / Q000503:physiopathology*; D014693:Ventricular Fibrillation / Q000209:etiology / Q000503:physiopathology
chemical_list: D000889:Anti-Arrhythmia Agents; D013015:Sotalol; D005424:Flecainide