Abstract 19505: Flecainide Increases AF Complexity by Enhancing Anisotropy in Goat Atria
Background: Despite its widespread clinical use for cardioversion of atrial fibrillation (AF), the mechanism by which flecainide (Flec) is able to restore sinus rhythm is still poorly understood. We hypothetized that Flec increases the degree of organization of fibrillatory conduction by increasing the size of activation wavefronts during AF.
Methods: AF was maintained for 3 weeks by burst pacing in goats (n=6), leading to persistent AF that could still be cardioverted pharmacologically. In arterially perfused excised hearts, fluorescence of di-4-ANEPPS was used to record atrial conduction patterns (spatial resolution 0.2 mm, 10 µM blebbistatin to eliminate contractions) during pacing at a cycle length of 400 ms and during induced AF episodes.
Results: Flec (2 µM) reduced the action potential duration (APD) from 115 ± 19 ms to 89 ± 14 ms, while reducing the macroscopic conduction velocity from 126 ± 11 to 80 ± 11 cm/s (both p<0.05). During local stimulation within the field of view, Flec caused a larger reduction in the tranverse than in the longitudinal conduction velocity (58 ± 6% vs 37 ± 6%), corresponding to an increase in anisotropy ratio from 1.9 ± 0.2 to 3.0 ± 0.3 (p<0.05). During AF, the reduction in transverse propagation was even more pronounced, with narrower fibrillation waves propagating in parallel to the local fiber orientation (figure). However, the diastolic interval during AF increased, leading to a longer activation cycle length.
Conclusion: Flecainide reduces the APD and increases conduction anisotropy. Contrary to our hypothesis, the size of activation wavefronts during AF was strongly reduced. However, Flec increased the diastolic interval during AF, consistent with a prolongation in either the excitable gap or post repolarization refractoriness. Left atrial area (2x2 cm) during local stimulation and AF. Snapshots during Flec show narrow fibrillation waves, while diastolic intervals increased (traces show optical action potentials during 2s of AF).
- © 2010 by American Heart Association, Inc.