Full Length ArticleFebuxostat attenuates paroxysmal atrial fibrillation-induced regional endothelial dysfunction

- Paroxysmal atrial fibrillation(PAF) can induce endothelial dysfunction(ED);
- PAF-induced ED occured to a greater extent in the left atrium;
- PAF-induced ED may related to xanthine oxidase(XO)-mediated oxidative stress;
- Febuxostat can attenuate PAF-induced ED and TAT generation by inhibition of XO and oxidative stress.

BackgroundParoxysmal atrial fibrillation (PAF) can increase thrombogenesis risk, especially in the left atrium (LA). The exact mechanism is still unclear.ObjectiveWe assessed the effects of PAF on endothelial function, and investigated if febuxostat (FX) can attenuate endothelial dysfunction by inhibition of xanthine oxidase (XO).Materials and methodsEighteen 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 7 days 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.Results and conclusionsEndothelial 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.