title: Asynchronous development of electrical remodeling and cardiac hypertrophy in the complete AV block dog.
abstract: OBJECTIVE
  Left ventricular hypertrophy has been associated with the prolongation of QT-time, and an increased risk of ventricular arrhythmias. The renin angiotensin system has been implicated in the development of ventricular hypertrophy. At 5 weeks complete AV block (CAVB) in the dog, there is: (1) biventricular hypertrophy associated with a transient activation of components of the renin angiotensin system, (2) increased APD, more pronounced in the left than in the right ventricle leading to spatial dispersion of repolarization, and (3) enhanced susceptibility to drug-induced torsade de pointes arrhythmias. To investigate whether these remodeling processes develop in parallel, time dependency was assessed in absence or presence of the AT1 receptor-blocker Irbesartan.
  
  
  RESULTS
  Dogs in sinus rhythm, 2 and 5 weeks CAVB were compared to dogs chronically treated with Irbesartan (30 mg/kg BID). Endocardial monophasic APD of left and right ventricle was measured and susceptibility to torsade de pointes was tested by infusing Dofetilide (0.025 mg/kg/5'). Hypertrophy was determined by relating heart-to-body weight at sacrifice. Left ventricular APD had increased more than right ventricular APD at 2 and 5 weeks CAVB, leading to an increase in spatial dispersion. At that time torsade de pointes were evocable in the majority of the dogs. Hypertrophy had only developed completely at 5 weeks CAVB. Irbesartan had no effect on electrical and structural parameters or on arrhythmogenicity.
  
  
  CONCLUSIONS
  In the CAVB dog ventricular hypertrophy is not a prerequisite for electrical remodeling or drug-induced torsade de pointes, and the AT1-receptor has no dominant role in the completion of these remodeling processes.
authors.affiliation: Department of Cardiology, Cardiovascular Research Institute Maastricht, PO Box 5800, 6202 AZ Maastricht, The Netherlands.
authors.forename: Marieke
authors.initials: M
authors.lastname: Schoenmakers
authors.forename: Christian
authors.initials: C
authors.lastname: Ramakers
authors.forename: Jurren M
authors.initials: JM
authors.lastname: van Opstal
authors.forename: Jet D M
authors.initials: JD
authors.lastname: Leunissen
authors.forename: Camila
authors.initials: C
authors.lastname: Londoño
authors.forename: Marc A
authors.initials: MA
authors.lastname: Vos
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology; D047228:Angiotensin II Type 1 Receptor Blockers; D001713:Biphenyl Compounds / Q000494:pharmacology; D001919:Bradycardia / Q000503:physiopathology*; D053818:Chymases; D004305:Dose-Response Relationship, Drug; D005260:Female; D006327:Heart Block; D006801:Humans; D017379:Hypertrophy, Left Ventricular / Q000503:physiopathology*; D000077405:Irbesartan; D008297:Male; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D010627:Phenethylamines; D026902:Potassium Channel Blockers; D012697:Serine Endopeptidases / Q000378:metabolism; D013449:Sulfonamides; D013777:Tetrazoles / Q000494:pharmacology; D016171:Torsades de Pointes / Q000139:chemically induced
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D001713:Biphenyl Compounds; D010627:Phenethylamines; D026902:Potassium Channel Blockers; D013449:Sulfonamides; D013777:Tetrazoles; D000804:Angiotensin II; D007703:Peptidyl-Dipeptidase A; D012697:Serine Endopeptidases; D053818:Chymases; D000077405:Irbesartan; C063533:dofetilide