title: Etiology-dependency of ionic remodeling in cardiomyopathic rabbits.
abstract: BACKGROUND
  Both dilated (DCM) and ischemic cardiomyopathy (ICM) are associated with action potential (AP) prolongation due to ionic remodeling. In humans, AP prolongation is more pronounced in myocytes isolated from explanted DCM than ICM hearts. However, there is a large variability due to confounding factors, including age, sex, concomitant disease, drug treatment, and progression of the disease at the time of heart transplantation. Here, we investigated the etiology-dependency of ionic remodeling in standardized rabbit models of ICM and DCM.
  
  
  METHODS
  ICM and DCM were induced by chronic infarction or combined volume and pressure overload, respectively. APs and membrane currents were measured using patch-clamp methodology.
  
  
  RESULTS
  Both ICM and DCM caused hypertrophy, but this hypertrophy was more prominent in DCM rabbits that also developed heart failure (DCM(F)), as revealed by the presence of ascites. Animals of either model showed AP prolongation. While the AP prolongation was similar by the same degree of hypertrophy, AP prolongation in DCM(F) was more pronounced. In all models, L-type Ca(2+) current, inward rectifier K(+) current, and rapid delayed rectifier K(+) current were unaltered, but the transient outward K(+) current (I(to 1)) density was significantly reduced. The I(to 1) decrease was not associated with differences in voltage-dependency of (in)activation. I(to 1) downregulation was similar in ICM and DCM with the same degree of hypertrophy, but was more pronounced in DCM(F).
  
  
  CONCLUSIONS
  The amount of ionic remodeling and AP prolongation in cardiomyopathic rabbits is due to differences in the amount of hypertrophy rather than differences in the etiology of the cardiomyopathy.
authors.affiliation: Heart Failure Research Center, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. A.O.Verkerk@amc.uva.nl
authors.forename: Arie O
authors.initials: AO
authors.lastname: Verkerk
authors.forename: Antonius
authors.initials: A
authors.lastname: Baartscheer
authors.forename: Joris R
authors.initials: JR
authors.lastname: de Groot
authors.forename: Ronald
authors.initials: R
authors.lastname: Wilders
authors.forename: Ruben
authors.initials: R
authors.lastname: Coronel
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000818:Animals; D020746:Calcium Channels, L-Type / Q000502:physiology; D006332:Cardiomegaly / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D002311:Cardiomyopathy, Dilated / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D002908:Chronic Disease; D051668:Delayed Rectifier Potassium Channels / Q000502:physiology; D004195:Disease Models, Animal; D006329:Heart Conduction System / Q000503:physiopathology*; D008297:Male; D009203:Myocardial Infarction / Q000150:complications / Q000473:pathology / Q000503:physiopathology; D017202:Myocardial Ischemia / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D018408:Patch-Clamp Techniques; D024661:Potassium Channels, Inwardly Rectifying / Q000502:physiology; D011817:Rabbits; D015222:Sodium Channels / Q000502:physiology; D020257:Ventricular Remodeling / Q000502:physiology
chemical_list: D020746:Calcium Channels, L-Type; D051668:Delayed Rectifier Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D015222:Sodium Channels