title: Febuxostat attenuates paroxysmal atrial fibrillation-induced regional endothelial dysfunction.
abstract: BACKGROUND
  Paroxysmal atrial fibrillation (PAF) can increase thrombogenesis risk, especially in the left atrium (LA). The exact mechanism is still unclear.
  
  
  OBJECTIVE
  We assessed the effects of PAF on endothelial function, and investigated if febuxostat (FX) can attenuate endothelial dysfunction by inhibition of xanthine oxidase (XO).
  
  
  METHODS
  Eighteen male New Zealand white rabbits were divided randomly into sham-operated (S), PAF (P) or FX+pacing (FP) groups. Group P and group FP received rapid atrial pacing (RAP). Group FP was administered febuxostat (FX) for 7days before RAP. Post-procedure, blood samples were collected from the LA, right atrium (RA) and peripheral circulation. Tissues from the LA and RA were obtained. Endothelial dysfunction (thrombomodulin [TM], von Willebrand factor [VWF], asymmetric dimethylarginine [ADMA]), and indirect thrombin generation (thrombin-antithrombin complex [TAT], prothrombin fragment 1+2 [F1.2]) and oxidative stress in atrial tissue (xanthine oxidase [XO], superoxide dismutase [SOD], malondialdehyde [MDA]) were measured using an Enzyme-linked immunosorbent assay. Atrial endothelial expression of TM and VWF was measured by histology/western blotting.
  
  
  CONCLUSIONS
  Endothelial dysfunction (TM, VWF, ADMA), TAT generation and oxidative stress (XO, SOD, MDA) in group P were more significant compared with that in group S (p<0.05, respectively). In group P, all of these changes occurred to a greater extent in the LA compared with those in the RA or peripheral circulation. In group FP, FX attenuated endothelial dysfunction and reduced TAT levels by inhibition of XO-mediated oxidative stress. PAF can lead to endothelial dysfunction and TAT generation by XO-mediated oxidative stress. The LA is more susceptible to these effects. FX can attenuate these changes by inhibition XO and XO-mediated oxidative stress.
authors.affiliation: Department of Cardiology, Chinese PLA General Hospital, Beijing 100853, China.
authors.forename: YanGuang
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Cardiology, Chinese PLA General Hospital, Beijing 100853, China.
authors.forename: FuKun
authors.initials: F
authors.lastname: Chen
authors.affiliation: Department of Cardiology, Chinese PLA General Hospital, Beijing 100853, China.
authors.forename: Long
authors.initials: L
authors.lastname: Deng
authors.affiliation: Department of Cardiology, Chinese PLA General Hospital, Beijing 100853, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Lin
authors.affiliation: Department of Cardiology, Chinese PLA General Hospital, Beijing 100853, China.
authors.forename: Xiangmin
authors.initials: X
authors.lastname: Shi
authors.affiliation: Department of Cardiology, Chinese PLA General Hospital, Beijing 100853, China.
authors.forename: Shan
authors.initials: S
authors.lastname: Zhaoliang
authors.affiliation: Department of Cardiology, Chinese PLA General Hospital, Beijing 100853, China. Electronic address: yutang2@me.com.
authors.forename: YuTang
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000818:Animals; D001281:Atrial Fibrillation / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004727:Endothelium / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D000069465:Febuxostat / Q000627:therapeutic use*; D006325:Heart Atria / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D011817:Rabbits; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D000069465:Febuxostat; D014969:Xanthine Oxidase
keywords: Endothelial dysfunction; Febuxostat; Oxidative stress; Paroxysmal atrial fibrillation; Thrombosis; Xanthine oxidase