title: Hyperglycemia aggravates atrial interstitial fibrosis, ionic remodeling and vulnerability to atrial fibrillation in diabetic rabbits.
abstract: OBJECTIVE
  The purpose of this study was to investigate the effects of hyperglycemia on atrial interstitial fibrosis, ionic remodeling and vulnerability to atrial fibrillation (AF) in alloxan-induced diabetic rabbits.
  
  
  METHODS
  Sixty Japanese rabbits were randomly assigned to alloxan-induced diabetic group (n=30) and control group (n=30). Ten rabbits in each group were respectively used to electrophysiological and histological study, patch-clamp study and Western blotting analysis. Langendorff perfusion was used to record inter-atrial conduction time (IACT), atrial effective refractory period (AERP) and dispersion (AERPD) and vulnerability to AF. Histological study was measured by Sirius-red stain. Patch-clamp technique was used to measure action potential duration (APD) and atrial ionic currents (INa and ICaL). Western blotting was applied to assess atrial protein expression of transforming growth factor beta 1 (TGFβ1).
  
  
  RESULTS
  Compared with control group, electrophysiological studies showed IACT was prolonged (37.91±6.81 vs. 27.43±1.63ms, p<0.01), AERPD was increased (30.37±8.33 vs. 14.70±5.16ms, p<0.01) in diabetic group. Inducibility of AF in diabetic group was significantly higher than in controls (8/10 vs. 1/10 of animals, p<0.01). Collagen volume fraction was increased (6.20±0.64% vs. 2.15±0.21%, p<0.01) in diabetic group. Patch-clamp studies demonstrated APD90 and APD50 were prolonged in diabetic rabbits (p<0.05 vs. control). The densities of INa were reduced and the densities of ICaL were increased (p<0.01 vs. control). Protein expression of TGFβ1 was increased in diabetic group (p<0.001 vs. control).
  
  
  CONCLUSIONS
  Our study suggests that hyperglycemia contributes to atrial interstitial fibrosis, ionic remodeling and vulnerability to AF in diabetic rabbits, resulting in atrial structural remodeling and electrical remodeling for the development and perpetuation of AF.
authors.affiliation: Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, Tianjin-People's Republic of China. liutongdoc@yahoo.com.cn.
authors.forename: Changle
authors.initials: C
authors.lastname: Liu
authors.forename: Huaying
authors.initials: H
authors.lastname: Fu
authors.forename: Jian
authors.initials: J
authors.lastname: Li
authors.forename: Wansong
authors.initials: W
authors.lastname: Yang
authors.forename: Lijun
authors.initials: L
authors.lastname: Cheng
authors.forename: Tong
authors.initials: T
authors.lastname: Liu
authors.forename: Guangping
authors.initials: G
authors.lastname: Li
mesh_terms: D000496:Alloxan / Q000494:pharmacology; D000818:Animals; D001281:Atrial Fibrillation / Q000150:complications / Q000503:physiopathology*; D064752:Atrial Remodeling; D003921:Diabetes Mellitus, Experimental; D004195:Disease Models, Animal; D004562:Electrocardiography; D005260:Female; D005355:Fibrosis / Q000503:physiopathology; D006325:Heart Atria / Q000503:physiopathology; D006943:Hyperglycemia / Q000150:complications / Q000503:physiopathology*; D008297:Male; D011817:Rabbits; D011897:Random Allocation; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: D053773:Transforming Growth Factor beta1; D000496:Alloxan