Roles of adrenergic and cholinergic stimulation in spontaneous atrial fibrillation in dogs

Abstract

Objectives: We studied the effects of beta-adrenergic and cholinergic stimulation and blockade on spontaneous atrial fibrillation (AF) in the intact dog heart.

Background: Paroxysmal AF is often preceded by changes in autonomic tone, but the relative roles of adrenergic and cholinergic influences on AF induction are not well known.

Methods: Perfusion of catecholamines and acetylcholine (ACh), as well as their combination, through the sinus node artery was used to induce AF in 20 anesthetized open-chest dogs without electrical stimulation of atria.

Results: Isoproterenol and adrenaline (10 to 100 micromol/l) induced AF in 21% (3 of 14) and 17% (1 of 6) of dogs, respectively. Atropine (1 to 2 mg) treatment prevented catecholamine-mediated AF, indicating a critical role of cholinergic tone in these AF episodes. Acetylcholine (2.8 +/- 0.3 micromol/l) induced AF in all dogs. Beta-blockade by propranolol (1 mg/kg) did not prevent ACh-induced AF, but increased the threshold ACh concentration for AF induction to 23.5 +/- 3.4 micromol/l (p < 0.05). Acetylcholine-mediated AF was facilitated by isoproterenol (1 to 2 and 10 micromol/l), which decreased the threshold ACh concentration for AF induction to 0.5 +/- 0.1 and 0.4 +/- 0.1 micromol/l, respectively (p < 0.05) and increased the AF duration (from 25 +/- 7 to 141 +/- 54 and 233 +/- 60 s, respectively; p < 0.05). Epicardial mapping of the right atrium (112 unipolar electrodes) demonstrated similar activation patterns during arrhythmias induced by ACh and catecholamines.

Conclusions: These data indicate that although both autonomic systems play a role in AF, cholinergic stimulation is likely the main factor for spontaneous AF initiation in this animal model. Adrenergic tone modulates the initiation and maintenance of cholinergically mediated AF.