title: Electrophysiological determinants of arrhythmic susceptibility upon endocardial and epicardial pacing in guinea-pig heart.
abstract: OBJECTIVE
  Endocardial pacing instituted to treat symptomatic bradycardia may nevertheless promote tachyarrhythmia in some pacemaker-implanted patients. We sought to determine the contributing electrophysiological mechanisms.
  
  
  METHODS
  Left ventricular (LV) monophasic action potential duration (APD(90)) and effective refractory periods were determined in perfused guinea-pig hearts along with volume-conducted ECG recordings during epicardial and endocardial stimulations.
  
  
  RESULTS
  Consistent with electrotonic modulation of repolarization, APD(90) at a given (either epicardial or endocardial) recording site tended to be longer while pacing from the ipsilateral LV site as compared to stimulations applied at the opposite side of ventricular wall. As a result, the intrinsic transmural repolarization gradient was amplified during endocardial pacing while being significantly reduced upon epicardial stimulations. The maximum slope of APD(90) restitution was greater upon endocardial than epicardial pacing. The excitability was found to recur at earlier repolarization time point at endocardium than epicardium, thereby contributing to increased endocardial critical intervals for re-excitation. Premature extrasystolic beats could have been elicited at shorter coupling stimulation intervals and propagated with greater transmural conduction delay upon endocardial than epicardial stimulations. Endocardial site exhibited lower ventricular fibrillation thresholds and greater inducibility of tachyarrhythmia upon extrasystolic stimulations as compared to epicardium.
  
  
  CONCLUSIONS
  Arrhythmic susceptibility in guinea-pig heart is greater during endocardial than epicardial pacing because of greater transmural APD(90) dispersion, steeper electrical restitution slopes, greater critical intervals for LV re-excitation and slower transmural conduction of the earliest premature ectopic beats. Further studies are warranted to determine whether these effects may contribute to proarrhythmia in paced human patients.
authors.affiliation: The Danish National Research Foundation Centre for Cardiac Arrhythmia, Department of Biomedical Sciences, The Panum Institute, University of Copenhagen, Copenhagen N, Denmark. osadchii@mail.ru
authors.forename: O E
authors.initials: OE
authors.lastname: Osadchii
mesh_terms: D000200:Action Potentials; D000818:Animals; D001145:Arrhythmias, Cardiac; D002304:Cardiac Pacing, Artificial; D004558:Electric Stimulation; D006168:Guinea Pigs; D006321:Heart / Q000502:physiology*; D006329:Heart Conduction System / Q000502:physiology*; D006352:Heart Ventricles / Q000503:physiopathology; D009200:Myocardial Contraction / Q000502:physiology