title: Arrhythmogenic Remodeling in Murine Models of Deoxycorticosterone Acetate-Salt-Induced and 5/6-Subtotal Nephrectomy-Salt-Induced Cardiorenal Disease.
abstract: BACKGROUND
  Renal failure is associated with adverse cardiac remodeling and sudden cardiac death. The mechanism leading to enhanced arrhythmogenicity in the cardiorenal syndrome is unclear. The aim of this study was to characterize electrophysiological and tissue alterations correlated with enhanced arrhythmogenicity in two distinct mouse models of renal failure.
  
  
  METHODS
  Thirty-week-old 129Sv mice received a high-salt diet and deoxycorticosterone acetate (DOCA) for 8 weeks, followed by an additional period of high-salt diet for 27 weeks (DOCA-salt aged model). Adult CD-1 mice were submitted to 5/6-subtotal nephrectomy (SNx) and treated for 11 weeks with a high-salt diet (SNx-salt adult model). Vulnerability to arrhythmia as well as conduction velocities (CVs) of the hearts were determined ex vivo with epicardial mapping. Subsequently, the hearts were characterized for connexin 43 (Cx43) and fibrosis.
  
  
  RESULTS
  DOCA-salt and SNx-salt mice developed renal dysfunction characterized by albuminuria. Heart, lung and kidney weights were increased in DOCA-salt mice. Both DOCA-salt and SNx-salt mice were highly susceptible to ventricular arrhythmias. DOCA-salt mice had a significant decrease in both longitudinal and transversal CV in the left ventricle. Histological analysis revealed a significant reduction in Cx43 expression as well as an increase in interstitial fibrosis in both DOCA-salt and SNx-salt mice.
  
  
  CONCLUSIONS
  DOCA-salt and SNx-salt treatment induced renal dysfunction, which resulted in structural and electrical cardiac remodeling and enhanced arrhythmogenicity. The reduced Cx43 expression and increased fibrosis levels in these hearts are likely candidates for the formation of the arrhythmogenic substrate.
authors.affiliation: Department of Medical Physiology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Magda S C
authors.initials: MS
authors.lastname: Fontes
authors.affiliation: Department of Nephrology and Hypertension, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Diana A
authors.initials: DA
authors.lastname: Papazova
authors.affiliation: Department of Nephrology and Hypertension, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Arianne
authors.initials: A
authors.lastname: van Koppen
authors.affiliation: Department of Medical Physiology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Sanne
authors.initials: S
authors.lastname: de Jong
authors.affiliation: Department of Medical Physiology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Sanne M
authors.initials: SM
authors.lastname: Korte
authors.affiliation: Department of Nephrology and Hypertension, University Medical Center Utrecht, Utrecht, The Netherlands ; Department of Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Lennart G
authors.initials: LG
authors.lastname: Bongartz
authors.affiliation: Pathology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Tri Q
authors.initials: TQ
authors.lastname: Nguyen
authors.affiliation: Department of Medical Physiology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Marti F A
authors.initials: MF
authors.lastname: Bierhuizen
authors.affiliation: Department of Medical Physiology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Teun P
authors.initials: TP
authors.lastname: de Boer
authors.affiliation: Department of Medical Physiology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Toon A B
authors.initials: TA
authors.lastname: van Veen
authors.affiliation: Department of Nephrology and Hypertension, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Marianne C
authors.initials: MC
authors.lastname: Verhaar
authors.affiliation: Department of Nephrology and Hypertension, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Jaap A
authors.initials: JA
authors.lastname: Joles
authors.affiliation: Department of Medical Physiology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Harold V M
authors.initials: HV
authors.lastname: van Rijen
keywords: 5/6-Subtotal nephrectomy; Arrhythmias; Cardiorenal disease; Connexin 43; Deoxycorticosterone acetate; Fibrosis