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

https://doi.org/10.1016/j.jacc.2003.09.030Get rights and content
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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 μmol/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 μmol/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 μmol/l (p < 0.05). Acetylcholine-mediated AF was facilitated by isoproterenol (1 to 2 and 10 μmol/l), which decreased the threshold ACh concentration for AF induction to 0.5 ± 0.1 and 0.4 ± 0.1 μmol/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.

Abbreviations

ACh
acetylcholine
AF
atrial fibrillation
AFCL
atrial fibrillation cycle length
APB
atrial premature beat
FWRA
free wall of right atrium
IVC
inferior vena cava
RA
right atrium
RAA
right atrial appendage
SNA
sinus node artery
SVC
superior vena cava

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This study was supported by the Russian Foundation for Basic Research (grants 02-04-48304 and 00-15-97788).