Abstract 14702: Tranilast Prevents Development of Substrates for Atrial Fibrillation in a Canine Model of Atrial Tachycardia and Rapid Ventricular Response
Background: Tranilast is an anti-allergic agent which has multiple effects including inhibition of collagen synthesis. Previous studies reported tranilast prevents cardiac fibrosis; however, its effects on AF have not been elucidated. Thus, we assessed effects of tranilast on canine AF associated with atrial tachycardia and rapid ventricular response.
Methods: Twenty three beagles were allocated to tranilast (N=9), no-drug control (CTL, N=8) and sham (N=6) groups. Tranilast and CTL groups were subjected to 4-week atrial tachypacing (ATP, 400 bpm) without atrioventricular block. Tranilast was commenced (50 mg/kg/day, orally) 1 week before starting ATP, and continued throughout the protocol. Atrial electrical remodeling was evaluated by serial electrophysiological studies, and quantification of atrial fibrosis and western blot analysis of TGF-β1 performed.
Results: In CTL group, 4-week ATP shortened atrial effective refractory period (AERP, from 170±11 to 96±6 ms at basic cycle length 300ms, P<0.01) and prolonged the duration of AF (from 0.3±0.2 to 37±7 sec, P<0.01). In tranilast group, ATP shortened AERP (from 176±14 to 111±4 ms), but the degree of AERP shortening was smaller than that in CTL group (P<0.05). In addition, the duration of AF (5.9±4 sec, P<0.01) was shortened in tranilast vs. CTL groups. ATP impaired hemodynamic parameters in CTL group (left ventricular ejection fraction, from 56±5 to 25±1%, P<0.01; left atrial area, from 308±21 to 460±33 mm2, P<0.01), and increased atrial fibrosis (CTL 9.3±3.6 vs. Sham 0.8±0.3%, P<0.01). In tranilast group, ATP-induced atrial fibrosis (1.3±0.7%, P<0.01 vs. CTL) was prevented without affecting left ventricular ejection fraction (27±4%, NS vs. CTL) and left atrial area (443±31 mm2, NS vs. CTL). In CTL group, ATP increased expression of TGF-β1 (CTL 2.3±0.9 vs. Sham 1.5±0.8 as ratios relative to paired GAPDH, P<0.05); however, tranilast suppressed ATP-induced over expression of TGF-β1 (1.5±0.6, P<0.05 vs. CTL).
Conclusions: Tranilast suppresses AF perpetuation related to atrial tachycardia and rapid ventricular response by preventing atrial structural and electrical remodeling. TGF-β1 suppressing effect of tranilast may play an important role in the prevention of the development of AF substrate.
- © 2011 by American Heart Association, Inc.