title: Effect of botulinum toxin on inducibility and maintenance of atrial fibrillation in ovine myocardial tissue.
abstract: BACKGROUND
  Aberrant vagal stimulation may promote the generation and propagation of atrial fibrillation (AF). Researchers have suggested that botulinum toxin (BTX), a neurotoxin that decreases neural vagal stimulation, may decrease the incidence of postoperative AF. The exact electrophysiologic mechanism underlying the observations and histopathologic alterations associated with BTX are unclear.
  
  
  OBJECTIVE
  To investigate the electrophysiologic, functional, and histopathologic effects of BTX on fibrillation induction in ovine atria.
  
  
  METHODS
  Eight sheep underwent BTX injections into their pulmonary veins, atrial fat pads, and ventricular walls. Electrophysiology with pacing was performed at baseline and 7 days after injection to evaluate the atrial effective refractory period (ERP) and vulnerability to AF with and without vagal stimulation. Echocardiography was performed at baseline and day 7. After euthanasia, histopathologic analysis was performed.
  
  
  RESULTS
  Seven sheep completed the study. For both atria, there was significant shortening in the ERP with vagal stimulation versus no stimulation on day 0 but not on day 7. More aggressive pacing was required to induce AF in the left atrium on day 7 than on day 0. Echocardiography on day 7 showed no significant changes in ejection fraction or new wall-motion abnormalities of the left and right ventricle. Histopathologic analysis showed no significant adverse effects.
  
  
  CONCLUSIONS
  The subacute BTX effect reduced the vulnerability of atrial tissue to AF induction and reduced the vagal influence on atrial ERP shortening compared to baseline levels. Direct BTX injection did not cause myocardial dysfunction or histologic adverse effects.
authors.affiliation: Department of Cardiology, Texas Heart Institute, Houston, Texas.|Department of Internal Medicine, Section of Cardiology, Baylor College of Medicine, Houston, Texas.
authors.forename: Alireza
authors.initials: A
authors.lastname: Nazeri
authors.affiliation: Department of Cardiology, Texas Heart Institute, Houston, Texas.|Department of Internal Medicine, Section of Cardiology, Baylor College of Medicine, Houston, Texas.
authors.forename: Anand V
authors.initials: AV
authors.lastname: Ganapathy
authors.affiliation: Department of Cardiology, Texas Heart Institute, Houston, Texas.
authors.forename: Ali
authors.initials: A
authors.lastname: Massumi
authors.affiliation: Department of Cardiology, Texas Heart Institute, Houston, Texas.|Department of Internal Medicine, Section of Cardiology, Baylor College of Medicine, Houston, Texas.
authors.forename: Mehran
authors.initials: M
authors.lastname: Massumi
authors.affiliation: Cardiovascular Research Laboratories, Texas Heart Institute, Houston, Texas.
authors.forename: Egemen
authors.initials: E
authors.lastname: Tuzun
authors.affiliation: Department of Cardiology, Texas Heart Institute, Houston, Texas.
authors.forename: Raymond
authors.initials: R
authors.lastname: Stainback
authors.affiliation: Department of Cardiovascular Pathology, Texas Heart Institute, Houston, Texas.
authors.forename: Ana-Maria
authors.initials: AM
authors.lastname: Segura
authors.affiliation: Department of Biostatistics and Epidemiology, Texas Heart Institute, Houston, Texas.
authors.forename: Macarthur A
authors.initials: MA
authors.lastname: Elayda
authors.affiliation: Department of Cardiology, Texas Heart Institute, Houston, Texas.|Department of Internal Medicine, Section of Cardiology, Baylor College of Medicine, Houston, Texas.
authors.forename: Mehdi
authors.identifier: http://orcid.org/0000-0001-7176-5586
authors.initials: M
authors.lastname: Razavi
mesh_terms: D000818:Animals; D001281:Atrial Fibrillation / Q000503:physiopathology* / Q000517:prevention & control*; D001905:Botulinum Toxins / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D006329:Heart Conduction System / Q000187:drug effects* / Q000503:physiopathology*; D008297:Male; D012756:Sheep; D014630:Vagus Nerve / Q000187:drug effects / Q000503:physiopathology*
chemical_list: D001905:Botulinum Toxins
keywords: arrhythmia; atrial fibrillation; botulinum toxin; electrophysiology; ovine studies; vagal stimulation