title: Enhanced susceptibility for acquired torsade de pointes arrhythmias in the dog with chronic, complete AV block is related to cardiac hypertrophy and electrical remodeling.
abstract: BACKGROUND
  Chronic, complete AV block (CAVB) in the dog leads to ventricular hypertrophy, which has been described as an independent risk factor for arrhythmias. In this model, we examined (1) whether the short- and long-term electrical adaptations predispose to acquired torsade de pointes arrhythmias (TdP) and (2) the nature of the structural and functional adaptations involved.
  
  
  RESULTS
  We determined (1) endocardial right (RV) and left (LV) ventricular APD, DeltaAPD (LV APD-RV APD), presence of EADs at 0 weeks (acute: AAVB), and CAVB (6 weeks) and inducibility of TdP by pacing and d-sotalol (n=10); (2) steady-state and dynamic LV hemodynamics at 0 and 6 weeks (n=6); (3) plasma neurohumoral levels in time (n=7); (4) structural parameters of the LV and RV of CAVB dogs (n=6) compared with sinus rhythm (SR) dogs (n=6); and (5) expression of ventricular mRNA atrial natriuretic factor (ANF) in CAVB (n=4) and SR (n=4) dogs. Compared with AAVB, CAVB led to nonhomogeneous prolongation of LV and RV APD and different sensitivity for d-sotalol, leading to EADs (4 of 14 versus 9 of 18, P<0.05), increased DeltaAPD (45+/-30 versus 125+/-60 ms, P<0.05), and induction of TdP in most dogs (0% versus 60%, P<0.05). CAVB led to biventricular hypertrophy, whereas LV function was similar in AAVB and CAVB. The neurohumoral levels were transiently elevated. The LV and RV collagen and the capillary/fiber ratio remained normal, whereas ventricular ANF mRNA was not detectable.
  
  
  CONCLUSIONS
  The electrical remodeling occurring after CAVB predisposes the heart to acquired TdP, whereas the structural changes (hypertrophy) are successfully aimed at maintaining cardiac function.
authors.affiliation: From the Departments of Cardiology, Physiology, Anesthesiology and Pathology, Cardiovascular Research Institute, Maastricht, The Netherlands. m.vos@cardio.azm.nl
authors.forename: M A
authors.initials: MA
authors.lastname: Vos
authors.forename: S H
authors.initials: SH
authors.lastname: de Groot
authors.forename: S C
authors.initials: SC
authors.lastname: Verduyn
authors.forename: J
authors.initials: J
authors.lastname: van der Zande
authors.forename: H D
authors.initials: HD
authors.lastname: Leunissen
authors.forename: J P
authors.initials: JP
authors.lastname: Cleutjens
authors.forename: M
authors.initials: M
authors.lastname: van Bilsen
authors.forename: M J
authors.initials: MJ
authors.lastname: Daemen
authors.forename: J J
authors.initials: JJ
authors.lastname: Schreuder
authors.forename: M A
authors.initials: MA
authors.lastname: Allessie
authors.forename: H J
authors.initials: HJ
authors.lastname: Wellens
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000222:Adaptation, Physiological / Q000502:physiology; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000097:blood / Q000235:genetics; D006332:Cardiomegaly / Q000473:pathology / Q000503:physiopathology*; D002908:Chronic Disease; D003331:Coronary Vessels; D004195:Disease Models, Animal; D004285:Dogs; D004562:Electrocardiography; D004594:Electrophysiology; D005260:Female; D005355:Fibrosis; D015870:Gene Expression; D006327:Heart Block / Q000175:diagnosis / Q000473:pathology / Q000503:physiopathology*; D006352:Heart Ventricles / Q000473:pathology; D006439:Hemodynamics; D008297:Male; D009638:Norepinephrine / Q000097:blood; D009929:Organ Size; D012333:RNA, Messenger / Q000032:analysis; D016171:Torsades de Pointes / Q000175:diagnosis / Q000473:pathology / Q000503:physiopathology*
chemical_list: D012333:RNA, Messenger; D009320:Atrial Natriuretic Factor; D009638:Norepinephrine