Abstract 16453: Comparable Effects of Beta-blockers on Atrial Fibrillation Promotion and Atrial Remodeling in Dogs with Atrial Tachycardia. Beyond the Beta-blocking Action
Background: Beta-blockers are widely used for rate control in atrial fibrillation (AF). On the other hand, there is evidence that oxidative stress and inflammation contribute to the pathophysiology of AF. Effects of beta-blockers on atrial remodeling and its underling mechanisms are yet elucidated. Thus, we evaluated the effects of comparable beta-blockers, carvedilol (CAR), known to have antioxidant and anti-inflammatory properties beyond its beta-blocking action, and a selective beta-blocker, bisoprolol (BISO).
Methods: Dogs underwent atrial tachypacing (ATP) at 400 bpm for 2 weeks to induce atrial remodeling and divided into 4 groups; non-paced controls (NP, n=8), ATP-only (n=8), and ATP with either CAR (50 mg/day, n=6) or BISO (12.5 mg/day, n=3), begun 3 days prior to ATP onset. Serial EP studies were performed at baseline, 1- and 2-week of ATP. We also measured the value of serum derivatives of reactive oxidative metabolites (DROMs) as an oxidative stress marker and CRP levels at the end of the study.
Results: Mean duration of induced AF (DAF) was markedly increased (from 2±2 s to 722±316 s, p<0.05), and atrial effective refractory period (ERP) was significantly shortened (e.g. at basic cycle length 300 ms: from 136±4 ms to 95±4 ms, p<0.01) after 2- week of ATP. AF vulnerability (percentage of atrial sites where AF inducible by single extra stimuli) was also significantly increased after 2-week of ATP (61±11 % in ATP-only vs 7±5% in NP, p<0.05). ATP-induced increases in DAF and AF vulnerability were also prevented by CAR (42±40 s and 17±8 %, p<0.05 vs ATP-only), but not by BISO (1202±597 s and 42±11 %, p=NS vs ATP-only). CAR also attenuated ERP shortening (117±9 ms, p<0.05 vs ATP-only), while BISO did not (101±3 ms, p=NS vs ATP-only). DROMs were significantly increased in ATP-only dogs (165±7 Carr Unit vs 115±18 Carr Unit in NP, p<0.05), and CAR markedly prevented this increase in DROMs (113±12 Carr Unit, p<0.01 vs ATP-only). No significant differences were seen in CRP levels among the group.
Conclusions: ATP-induced AF promotion and atrial tachycardia remodeling were attenuated by carvedilol, but not by bisoprolol. These findings support the notion that beta-blockers with antioxidant properties, such as carvedilol, may be potentially useful against clinical AF.
- © 2010 by American Heart Association, Inc.