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Antiremodeling Effect of Xanthine Oxidase Inhibition in a Canine Model of Atrial Fibrillation
Tomoharu Yoshizawa1,2, Shinichi Niwano1, Hiroe Niwano3
1Department of Cardiovascular Medicine, Kitasato University School of Medicine.
Abstract:
In a canine rapid atrial stimulation model of atrial fibrillation (AF), we have demonstrated an increased production of reactive oxygen species (ROS) along with electrical and structural remodeling. In the present study, we hypothesized that antioxidants can suppress atrial remodeling canines with AF. We therefore evaluated the effect of febuxostat, a xanthine oxidase (XO) inhibitor and a pure antioxidant, on atrial remodeling.AF was produced by performing a 3-week rapid atrial pacing (400 bpm) in 13 dogs divided into three groups: pacing + febuxostat group (n = 5; atrial pacing with 50 mg/day of febuxostat (administration); pacing control group (n = 5; atrial pacing without any drug administration); and non-pacing group (n = 3). Electrophysiological studies were conducted in the first 2 groups every week. Atrial tissue fibrosis was evaluated by Azan and immunofluorescent staining of fibronectin. Oxidative stress was evaluated by DHE and FCF-DA staining.Shortening of the refractory period and increase in AF inducibility appeared gradually in the pacing control group, but such changes were suppressed in the pacing + febuxostat group (P = 0.05). The pacing control group showed increase in fibrosis, which was suppressed in the febuxostat group. In DHE and DCF-DA staining, the pacing control group showed an increase in oxidative stress, which was suppressed in the pacing + febuxostat group. The pacing control group exhibited fibronectin expression, which was suppressed in the pacing + febuxostat group.The antioxidant effect of febuxostat may achieve an inhibition of new-onset AF in canines.
Insights
Febuxostat, an antioxidant, suppressed atrial remodeling and reduced the inducibility of atrial fibrillation (AF) in canines. This suggests antioxidants may inhibit new-onset AF by mitigating oxidative stress and fibrosis.
Area of Science:
- Cardiology
- Pharmacology
- Biochemistry
Background:
- Atrial fibrillation (AF) is associated with increased reactive oxygen species (ROS) and cardiac remodeling.
- Antioxidants are hypothesized to mitigate AF-related atrial remodeling.
Purpose of the Study:
- To evaluate the effect of febuxostat, a xanthine oxidase (XO) inhibitor and antioxidant, on atrial remodeling in a canine model of AF.
Main Methods:
- Rapid atrial pacing (400 bpm) for 3 weeks in dogs, divided into pacing + febuxostat, pacing control, and non-pacing groups.
- Electrophysiological studies, Azan and immunofluorescent staining for fibronectin, and oxidative stress markers (DHE, FCF-DA) were used.
Main Results:
- Febuxostat suppressed the shortening of the refractory period and reduced AF inducibility compared to controls (P=0.05).
- Febuxostat inhibited atrial fibrosis, oxidative stress, and fibronectin expression in pacing-induced AF canines.
Conclusions:
- The antioxidant properties of febuxostat may inhibit new-onset atrial fibrillation in canines.
- Febuxostat demonstrates potential as a therapeutic agent for preventing AF progression by targeting oxidative stress and structural remodeling.
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