Electrophysiological and antiarrhythmic effects of the novel antiarrhythmic agent AZD7009: A comparison with azimilide and AVE0118 in the acutely dilated right atrium of the rabbit in vitro

Abstract

Aims: To compare the electrophysiological and antiarrhythmic effects of AZD7009, azimilide, and AVE0118 in the acutely dilated rabbit atria in vitro. Methods and results: In the isolated Langendorf-perfused rabbit heart, the atrial effective refractory period (AERP) and the inducibility of atrial fibrillation (AF) were measured at increasing concentrations of AZD7009 (0.1-3 μM), azimilide (0.1-3 μM), and AVE0118 (0.3-10 μM). In separate groups of atria, termination of sustained AF was assessed. In non-dilated atria, the AERP was 82 ± 1.3 ms (mean ± SEM) and AF could not be induced. Dilation significantly reduced the AERP to 49 ± 1.0 14; ms (P < 0.001) and 92% of the atria became inducible. Perfusion with AZD7009, azimilide, and AVE0118 concentration-dependently increased the AERP and reduced the AF inducibility. At the highest concentrations of AZD7009, azimilide, and AVE0118, AERP and AF inducibility changed from 50 ± 4.5 to 136 ± 6.6 ms and 80 to 0% (both P < 0.001) from 51 ± 3.0 to 105 ± 9.9 ms (P < 0.001) and 80 to 0% (P < 0.01) and from 46 ± 2.8 to 85 ± 6.0 ms and 90 to 0% (both P < 0.001). Restoration of sinus rhythm was seen in 6/6, 5/6, and 5/6 hearts perfused with AZD7009, azimilide, and AVE0118, respectively. Conclusion: In the dilated rabbit atria, AZD7009, azimilide, and AVE0118 concentration-dependently increased AERP, effectively prevented AF induction, and rapidly restored sinus rhythm. © 2006 Oxford University Press.