title: Flecainide attenuates rate adaptation of ventricular repolarization in guinea-pig heart.
abstract: OBJECTIVE
  Flecainide is class Ic antiarrhythmic agent that was found to increase the risk of sudden cardiac death. Arrhythmic responses to flecainide could be precipitated by exercise, suggesting a role played by inappropriate rate adaptation of ventricular repolarization. This study therefore examined flecainide effect on adaptation of the QT interval and ventricular action potential duration (APD) to abrupt reductions of the cardiac cycle length.
  
  
  METHODS
  ECG and ventricular epicardial and endocardial monophasic APD were recorded in isolated, perfused guinea-pig heart preparations upon a sustained cardiac acceleration (rapid pacing for 30 s), and following a single perturbation of the cycle length evoked by extrasystolic stimulation.
  
  
  RESULTS
  Sustained increase in heart rate was associated with progressive bi-exponential shortening of the QT interval and APD. Flecainide prolonged ventricular repolarization, delayed its rate adaptation, and decreased the amplitude of QT interval and APD shortening upon rapid cardiac pacing. During extrasystolic stimulation, flecainide attenuated APD shortening in premature ventricular beats, with effect being greater upon using a longer basic drive cycle length (S1-S1=550 ms versus S1-S1=300 ms).
  
  
  CONCLUSIONS
  Flecainide-induced arrhythmia may be partly accounted for by attenuated adaptation of ventricular repolarization to sudden changes in cardiac cycle length provoked by transient tachycardia or ectopic beats.
authors.affiliation: a Department of Biomedical Sciences , University of Copenhagen , Copenhagen N , Denmark.|b Department of Health Science and Technology , University of Aalborg , Aalborg , Denmark.
authors.forename: Oleg E
authors.initials: OE
authors.lastname: Osadchii
mesh_terms: D000200:Action Potentials; D000222:Adaptation, Physiological; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001145:Arrhythmias, Cardiac / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D002304:Cardiac Pacing, Artificial; D004195:Disease Models, Animal; D004562:Electrocardiography; D022062:Electrophysiologic Techniques, Cardiac; D005424:Flecainide / Q000494:pharmacology*; D006168:Guinea Pigs; D006339:Heart Rate / Q000187:drug effects*; D006352:Heart Ventricles / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D026941:Sodium Channel Blockers / Q000494:pharmacology*; D016277:Ventricular Function, Left / Q000187:drug effects*; D016278:Ventricular Function, Right / Q000187:drug effects*
chemical_list: D000889:Anti-Arrhythmia Agents; D026941:Sodium Channel Blockers; D005424:Flecainide
keywords: Cardiac arrhythmia; flecainide; rate adaptation; ventricular repolarization