title: Contractile adaptations preserving cardiac output predispose the hypertrophied canine heart to delayed afterdepolarization-dependent ventricular arrhythmias.
abstract: BACKGROUND
  In dogs, chronic complete atrioventricular block (CAVB) results in structural (biventricular hypertrophy) and electrical (delayed repolarization) remodeling, which predisposes the heart to torsade de pointes arrhythmias. We assessed the contractile alterations in the CAVB dog and tested the hypothesis that these adaptations increase delayed afterdepolarization (DAD)-dependent triggered arrhythmias.
  
  
  RESULTS
  Steady-state and dynamic (fast pacing: 1 to 68 stimuli) left and right ventricular systolic and diastolic parameters were determined by positive and negative inotropic interventions at acute AVB and CAVB. Concomitantly, left and right ventricular endocardial monophasic action potentials were registered. In CAVB, all systolic contractile parameters were markedly increased, resulting in preserved cardiac output. The increase was most pronounced at low heart rates, altering the force-frequency response. At both acute AVB and CAVB, the degree of potentiation of cardiac function with pacing was dependent on the number of stimuli and showed a maximum at 8 to 13 stimuli. With CAVB, this potentiation curve was shifted upward, and it was only then that pacing resulted in DADs (in 8 of 10 dogs) and ectopic beats (EBs, in 6 of 10 dogs). The incidence of EBs in relation to the number of stimuli also had a maximum at 8 to 13 stimuli. Ouabain increased the incidence of DADs and EBs, whereas the negative inotropic interventions prevented them completely.
  
  
  CONCLUSIONS
  The alterations responsible for improvement in systolic contractile function in CAVB dogs predispose the hypertrophied heart to DAD-dependent triggered arrhythmias during positive inotropic interventions.
authors.affiliation: Department of Cardiology, Cardiovascular Research Institute Maastricht, Academic Hospital Maastricht, Netherlands.
authors.forename: S H
authors.initials: SH
authors.lastname: de Groot
authors.forename: M
authors.initials: M
authors.lastname: Schoenmakers
authors.forename: M M
authors.initials: MM
authors.lastname: Molenschot
authors.forename: J D
authors.initials: JD
authors.lastname: Leunissen
authors.forename: H J
authors.initials: HJ
authors.lastname: Wellens
authors.forename: M A
authors.initials: MA
authors.lastname: Vos
mesh_terms: D000220:Adaptation, Biological; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000209:etiology*; D002302:Cardiac Output; D006332:Cardiomegaly / Q000503:physiopathology*; D004195:Disease Models, Animal; D004285:Dogs; D005260:Female; D006327:Heart Block / Q000503:physiopathology*; D006352:Heart Ventricles / Q000503:physiopathology; D008297:Male; D009200:Myocardial Contraction