Idiopathic atrial fibrillation in dogs: electrophysiologic determinants and mechanisms of antiarrhythmic action of flecainide.

OBJECTIVES This study sought to determine the mechanisms of idiopathic atrial fibrillation and the atrial antifibrillatory action of flecainide in dogs. BACKGROUND In a small subset of dogs, sustained atrial fibrillation can be readily induced in the absence of vagal tone. The electrophysiologic mechanisms underlying this ability to sustain atrial fibrillation, and of flecainide action on the arrhythmia, are unknown. METHODS Six dogs with inducible sustained atrial fibrillation were studied before and after flecainide administration and compared with a control group of 10 dogs. RESULTS Dogs with atrial fibrillation differed in displaying more shortening of the atrial refractory period with increased rate, resulting in a significantly shorter refractory period and wavelength for reentry at rapid rates, and in increased regional dispersion in refractoriness. Activation maps during sustained fibrillation showed a mean (+/- SE) of 6.3 +/- 0.4 coexistent zones of reentry, compatible with short wavelengths, whereas in control dogs activation during self-limited atrial fibrillation was better organized, and the number of reentrant circuits was smaller. Quantitative analysis demonstrated significantly greater inhomogeneity of activation during atrial fibrillation in dogs with atrial fibrillation than in control animals. Flecainide terminated atrial fibrillation by increasing the duration and homogeneity of atrial refractoriness at rapid rates, thereby reducing the number of reentry circuits and the heterogeneity of activation. CONCLUSIONS The ability of atrial fibrillation to sustain itself resulted from enhanced rate-dependent shortening of atrial refractoriness and increased regional heterogeneity. Flecainide reversed these changes and restored sinus rhythm. These results suggest potential mechanisms of idiopathic atrial fibrillation and are pertinent to understanding the clinical actions of flecainide.