Xanthine Oxidase Inhibition Prevents Atrial Fibrillation in a Canine Model of Atrial Pacing‐Induced left Ventricular Dysfunction

Allopurinol and Atrial Fibrillation . Aims: Oxidative stress could be a possible mechanism and a therapeutic target of atrial fibrillation (AF). Xanthine oxidase (XO) inhibition reduces oxidative stress, but the effects of XO inhibitor on AF have not been evaluated. Hence, we assessed the effects of XO inhibitor, allopurinol, on progression of atrial vulnerability in dogs associated with tachycardia‐induced cardiomyopathy. Methods and Results: The dogs were subjected to atrial tachypacing (ATP, 400 bpm) without atrioventricular block for 4 weeks. The dynamics of atrial‐tachycardia remodeling were evaluated in allopurinol‐treated dogs (ALO, n = 5), placebo‐treated controls (CTL, n = 6), and sham‐operated dogs (n = 6). In CTL dogs, 4 weeks of ATP significantly increased AF duration (DAF; from 0.2 ± 0.2 seconds to 173 ± 67 seconds, P < 0.05) and decreased atrial effective refractory period (ERP; from 152 ± 9 milliseconds to 80 ± 4 milliseconds at a cycle length of 350 milliseconds, P < 0.01). Allopurinol attenuated the ATP effects on ERP (118 ± 6 milliseconds, P < 0.01) or DAF (0.6 ± 0.3 seconds, P < 0.05). In CTL dogs, ATP‐induced rapid ventricular responses decreased left ventricular ejection fraction (LVEF; from 58.6 ± 0.1 to 23.5 ± 2.4%, P < 0.01), and increased left atrial diameter (LAD; from 17 ± 1 mm to 24 ± 1 mm, P < 0.01). ATP increased atrial fibrosis when compared with sham‐operated dogs (CTL 10.7 ± 0.8% vs Sham 1.1 ± 0.3%, P < 0.01). Allopurinol suppressed atrial fibrosis (2.3 ± 0.6%, P < 0.01 vs CTL) and eNOS reduction without affecting LVEF (20.6 ± 2.2%, ns) and LAD (23 ± 1 mm, ns). Conclusion: Allopurinol suppresses AF promotion by preventing both electrical and structural remodeling. These results suggest that XO may play an important role in enhancement of atrial vulnerability, and might be a novel target of AF therapy. (J Cardiovasc Electrophysiol, Vol. 23 pp. 1130‐1135, October 2012)