**8. Xanthine oxidase inhibitors**

Accumulating evidence suggests that xanthine oxidase (XO) is another important source of ROS and may relate to atrial remodeling and AF [81]. In a pig model of rapid atrial pacing, increased XO activity in LAA and reduced superoxide production by 85% following admin‐ istration of oxypurinol (a XO inhibitor) was demonstrated [75]. However, no significant effect of oxypurinol on superoxide production in human RAA was demonstrated in another study [76]. A potential explanation for this evident difference is that in the porcine model the increased XO activity was located in the LAA, whereas RAA specimens were examined in the human study. Of note, in a similar porcine model, it was demonstrated that after 1 week of rapid atrial pacing NO expression was decreased in the LAA but not in the RAA, indicating that the oxidative stress was enhanced only in the left atrium [82].

**Acknowledgements**

**Author details**

**References**

Science Foundation of China.

Tong Liu1\*, Panagiotis Korantzopoulos2

Conflict of interest: None declared

115, 135-143.

306-313.

262-268.

13, 308-328.

\*Address all correspondence to: liutongdoc@yahoo.com.cn

Medical University, Tianjin, People's Republic of China

This work was supported by grants (30900618, 81270245 to T.L.) from the National Natural

Antioxidant Therapies in the Prevention and Treatment of Atrial Fibrillation

http://dx.doi.org/10.5772/53408

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and Guangping Li1

1 Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin

[1] Korantzopoulos, P, Kolettis, T. M, Galaris, D, & Goudevenos, J. A. The role of oxidative stress in the pathogenesis and perpetuation of atrial fibrillation. *Int J Cardiol* (2007). ,

[2] Van Wagoner, D. R. Oxidative stress and inflammation in atrial fibrillation: Role in pathogenesis and potential as a therapeutic target. *J Cardiovasc Pharmacol* (2008). , 52,

[3] Huang, C. X, Liu, Y, Xia, W. F, Tang, Y. H, & Huang, H. Oxidative stress: A possible

[4] Negi, S, Sovari, A. A, & Dudley, S. C. Jr. Atrial fibrillation: The emerging role of inflammation and oxidative stress. *Cardiovasc Hematol Disord Drug Targets* (2010). , 10,

[5] Jeong, E. M, Liu, M, Sturdy, M, et al. Metabolic stress, reactive oxygen species, and

[6] Savelieva, I, Kakouros, N, Kourliouros, A, & Camm, A. J. Upstream therapies for management of atrial fibrillation: Review of clinical evidence and implications for european society of cardiology guidelines. Part I: Primary prevention. *Europace* (2011). ,

[7] Savelieva, I, Kakouros, N, Kourliouros, A, & Camm, A. J. Upstream therapies for management of atrial fibrillation: Review of clinical evidence and implications for

pathogenesis of atrial fibrillation. *Med Hypotheses* (2009). , 72, 466-467.

arrhythmia. *J Mol Cell Cardiol* (2012). , 52, 454-463.

2 Department of Cardiology, University of Ioannina Medical School, Ioannina, Greece

UA is a metabolic product of purine metabolism produced via the action of XO. Therefore, UA represents a marker of oxidative stress and inflammation [83, 84]. There is a positive association between UA levels and AF in different population. In a small observational study, we showed a stepwise increase of UA levels in patients with paroxysmal AF and permanent AF compared to controls [85]. It was also demonstrated that high serum UA levels were independent predictor for AF presence in hypertensive patients [86] and AF recurrence following catheter ablation [87]. In the ARIC study, a large prospective cohort study, elevated serum UA was associated with a greater risk of AF development during the follow-up period [88].

No clinical trial to date has examined the effect of allopurinol administration on AF. Only one observational study reported that patients receiving UA lowering agents had decreased AF prevalence [89]. In a very recent experimental study using a dog model of atrial tachypacing, allopurinol suppressed AF promotion by preventing both electrical and structural remodeling, while it also reduced endothelial NOS protein expression without affecting the left ventricular ejection fraction or LA diameter [90]. Finally, there are no data on the cardiovascular effects of the newly released non-purine XO inhibitor febuxostat.
