A Canine Model of Sustained Atrial Fibrillation Induced by Rapid Atrial Pacing and Phenylephrine

Atrial fibrillation is a common arrhythmia with considerable morbidity and mortality. Limitations in studying both the mechanisms and therapy of atrial fibrillation arise due to the paucity of models that yield sufficiently high-quality data, are not costly, and in which atrial fibrillation is sustained long enough to make the necessary observations. The canine model we present is based on the hypothesis that atrial fibrillation requires heterogeneity of repolarization, that distribution of vagal fibers is heterogeneous in the atria, and that atrial fibrillation will persist after reflex stimulation of vagal efferents by increased systemic arterial pressure. Dogs were anesthetized with morphine–chloralose because this combination maintains nearly intact autonomic control. Systemic arterial pressure was elevated approximately 75 mm Hg during infusion of phenylephrine (2 μg/kg · min⁻¹). The right atrium was paced for 20 min at 40 Hz. Atrial fibrillation was sustained after cessation of atrial pacing in dogs receiving phenylephrine, but terminated within seconds in normotensive animals. In conclusion, atrial fibrillation can be maintained for at least 40 min after cessation of rapid atrial pacing in dogs with phenylephrine-induced hypertension.Atrial fibrillation is a common arrhythmia that affects more than 2 million persons in the United States.¹ This condition is characterized by chaotic asynchronous activation and contraction of hundreds of regions of the atria, resulting in both absence of active atrial transport of blood and a rapid ventricular response. With chronic atrial fibrillation, patients can develop thromboembolism and stroke;²² and 15% of strokes in the United States occur in patients with atrial fibrillation.¹ Despite prodigious efforts to understand the mechanism of this condition and to prevent and remediate it, atrial fibrillation leads to enormous morbidity and mortality.³ One factor hindering studies of atrial fibrillation is the absence of a model in which fibrillation can be sustained for more than several seconds, although the arrhythmia can be sustained nearly permanently after weeks of rapid atrial pacing in animals with either heart failure or physical injury to the left atrium.⁸Rapid atrial pacing decreases the atrial effective refractory period, slows atrial conduction, and increases electrophysiologic heterogeneity.^10,11,20 Recently, phenylephrine was shown to increase the difference between left and right atrial and intraatrial refractory periods, thus creating heterogeneity of atrial refractoriness.¹⁶ We therefore postulated that rapid atrial pacing together with phenylephrine infusion would induce relatively sustained atrial fibrillation for at least 40 min in dogs—a duration likely to be sufficient for testing of agents with potential to convert atrial fibrillation. This report describes a simple canine model using rapid atrial pacing in which atrial fibrillation was sustained for at least 40 min.