Roles of adrenergic and cholinergic stimulation in spontaneous atrial fibrillation in dogs
Oleg F. Sharifov, MD, PhD* ,*,
Vadim V. Fedorov, PhD*,
Galina G. Beloshapko, PhD*,
Alexey V. Glukhov, MS*,
Anna V. Yushmanova, PhD* and
Leonid V. Rosenshtraukh, PhD*
* Laboratory of Heart Electrophysiology, Cardiology Research Center, Moscow, Russia
Department of Biomedical Engineering, University of Alabama at Birmingham, Birmingham, Alabama, USA
Manuscript received March 28, 2003;
revised manuscript received August 15, 2003,
accepted September 17, 2003.
* Reprint requests and correspondence: Dr. Oleg F. Sharifov, University of Alabama at Birmingham, 1670 University Boulevard, VH B165, Birmingham, Alabama 35294-0019, USA.
sharifov{at}crml.uab.edu
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.
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Abbreviations and Acronyms
| | 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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