Mechanisms of stretch-induced atrial fibrillation in the presence and the absence of adrenocholinergic stimulation: interplay between rotors and focal discharges.
BACKGROUND
Both atrial stretch and combined adrenocholinergic stimulation (ACS) have been shown to favor initiation and maintenance of atrial fibrillation (AF). Their respective contributions to the electrophysiological mechanism remains, however, incompletely understood.


OBJECTIVE
This study endeavored to determine the mechanism of maintenance of stretch-related AF (SRAF) in the presence and absence of ACS and to assess how focal discharges interact with rotors to modify the level of complexity in the activation patterns to perpetuate AF.


METHODS
Video imaging of AF dynamics was carried out using a SRAF model in isolated sheep hearts (n = 24). Pharmacological approaches were used to (1) mimic ACS with acetylcholine (1 microM) plus isoproterenol (0.03 microM), and (2) abolish triggered activity, in response to sarcoplasmic reticulum calcium release, with caffeine (5 mM, CA) or ryanodine (10 to 40 microM, RYA).


RESULTS
In the absence of ACS, on perfusion of CA or RYA, focal discharges were abolished and SRAF was terminated in most of the cases (10 of 13 experiments). In the presence of ACS, multiple drifting rotors as well as a large number of focal discharges were identified and only 1 of 11 AF episodes was terminated.


CONCLUSIONS
In the absence of ACS, SRAF is maintained by high-frequency focal discharges that generate fibrillatory conduction and wave breaks. In the presence of ACS, SRAF dynamics is characterized by multiple high frequency rotors that are rendered unstable by spatially distributed focal discharges.
Yamazaki
Masatoshi
M
Center for Arrhythmia Research, University of Michigan, Ann Arbor, Michigan 48108, USA.
Vaquero
Luis M
LM
Hou
Luqia
L
Campbell
Katherine
K
Zlochiver
Sharon
S
Klos
Matthew
M
Mironov
Sergey
S
Berenfeld
Omer
O
Honjo
Haruo
H
Kodama
Itsuo
I
Jalife
José
J
Kalifa
Jérôme
J
D000109:Acetylcholine / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D001281:Atrial Fibrillation / Q000209:etiology / Q000503:physiopathology*; D018678:Cholinergic Agents / Q000494:pharmacology*; D004195:Disease Models, Animal; D006321:Heart / Q000187:drug effects*; D007545:Isoproterenol / Q000494:pharmacology; D012756:Sheep; D014741:Video Recording
D000318:Adrenergic beta-Agonists; D018678:Cholinergic Agents; D007545:Isoproterenol; D000109:Acetylcholine