Roles of adrenergic and cholinergic stimulation in spontaneous atrial fibrillation in dogs.
OBJECTIVE
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.
Sharifov
Oleg F
OF
Laboratory of Heart Electrophysiology, Cardiology Research Center, Moscow, Russia. sharifov@crml.uab.edu
Fedorov
Vadim V
VV
Beloshapko
Galina G
GG
Glukhov
Alexey V
AV
Yushmanova
Anna V
AV
Rosenshtraukh
Leonid V
LV
D000109:Acetylcholine / Q000494:pharmacology; D000322:Adrenergic Agonists / Q000494:pharmacology*; D018674:Adrenergic Antagonists / Q000494:pharmacology*; D000818:Animals; D001281:Atrial Fibrillation / Q000503:physiopathology*; D001285:Atropine / Q000494:pharmacology; D018679:Cholinergic Agonists / Q000494:pharmacology*; D018680:Cholinergic Antagonists / Q000494:pharmacology*; D004285:Dogs; D004837:Epinephrine / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D023421:Models, Animal; D011433:Propranolol / Q000494:pharmacology; D012849:Sinoatrial Node / Q000187:drug effects*
D000322:Adrenergic Agonists; D018674:Adrenergic Antagonists; D018679:Cholinergic Agonists; D018680:Cholinergic Antagonists; D001285:Atropine; D011433:Propranolol; D007545:Isoproterenol; D000109:Acetylcholine; D004837:Epinephrine