title: Myocardial impulse propagation is impaired in right ventricular tissue of Zucker diabetic fatty (ZDF) rats.
abstract: BACKGROUND
  Diabetes increases the risk of cardiovascular complications including arrhythmias, but the underlying mechanisms remain to be established. Decreased conduction velocity (CV), which is an independent risk factor for re-entry arrhythmias, is present in models with streptozotocin (STZ) induced type 1 diabetes. Whether CV is also disturbed in models of type 2 diabetes is currently unknown.
  
  
  METHODS
  We used Zucker Diabetic Fatty (ZDF) rats, as a model of type 2 diabetes, and their lean controls Zucker Diabetic Lean (ZDL) rats to investigate CV and its response to the anti-arrhythmic peptide analogue AAP10. Gap junction remodeling was examined by immunofluorescence and western blotting. Cardiac histomorphometry was examined by Masson`s Trichrome staining and intracellular lipid accumulation was analyzed by Bodipy staining.
  
  
  RESULTS
  CV was significantly slower in ZDF rats (56±1.9 cm/s) compared to non-diabetic controls (ZDL, 66±1.6 cm/s), but AAP10 did not affect CV in either group. The total amount of Connexin43 (C×43) was identical between ZDF and ZDL rats, but the amount of lateralized C×43 was significantly increased in ZDF rats (42±12 %) compared to ZDL rats (30±8%), p<0.04. Judged by electrophoretic mobility, C×43 phosphorylation was unchanged between ZDF and ZDL rats. Also, no differences in cardiomyocyte size or histomorphometry including fibrosis were observed between groups, but the volume of intracellular lipid droplets was 4.2 times higher in ZDF compared to ZDL rats (p<0.01).
  
  
  CONCLUSIONS
  CV is reduced in type 2 diabetic ZDF rats. The CV disturbance may be partly explained by increased lateralization of C×43, but other factors are likely also involved. Our data indicates that lipotoxicity potentially may play a role in development of conduction disturbances and arrhythmias in type 2 diabetes.
authors: The Danish National Research Foundation Centre for Cardiac Arrhythmia and Department of Biomedical Sciences, Faculty of Health Sciences, University of Copenhagen, Blegdamsvej 3, Copenhagen DK-2200, Denmark.
authors: Kristine Boisen
authors: KB
authors: Olsen
authors: Lene Nygaard
authors: LN
authors: Axelsen
authors: Thomas Hartig
authors: TH
authors: Braunstein
authors: Charlotte Mehlin
authors: CM
authors: Sørensen
authors: Claus B
authors: CB
authors: Andersen
authors: Thorkil
authors: T
authors: Ploug
authors: Niels-Henrik
authors: NH
authors: Holstein-Rathlou
authors: Morten Schak
authors: MS
authors: Nielsen
mesh_terms: D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology*; D006321:Heart / Q000502:physiology*; D006329:Heart Conduction System / Q000503:physiopathology*; D006352:Heart Ventricles / Q000503:physiopathology*; D008297:Male; D009206:Myocardium / Q000473:pathology; D009924:Organ Culture Techniques; D051381:Rats; D011924:Rats, Zucker