title: Mechanisms of stretch-induced atrial fibrillation in the presence and the absence of adrenocholinergic stimulation: interplay between rotors and focal discharges.
abstract: 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.
authors: Center for Arrhythmia Research, University of Michigan, Ann Arbor, Michigan 48108, USA.
authors: Masatoshi
authors: M
authors: Yamazaki
authors: Luis M
authors: LM
authors: Vaquero
authors: Luqia
authors: L
authors: Hou
authors: Katherine
authors: K
authors: Campbell
authors: Sharon
authors: S
authors: Zlochiver
authors: Matthew
authors: M
authors: Klos
authors: Sergey
authors: S
authors: Mironov
authors: Omer
authors: O
authors: Berenfeld
authors: Haruo
authors: H
authors: Honjo
authors: Itsuo
authors: I
authors: Kodama
authors: José
authors: J
authors: Jalife
authors: Jérôme
authors: J
authors: Kalifa
mesh_terms: 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
chemical_list: D000318:Adrenergic beta-Agonists; D018678:Cholinergic Agents; D007545:Isoproterenol; D000109:Acetylcholine