title: Antiarrhythmic effects of vasostatin-1 in a canine model of atrial fibrillation.
abstract: BACKGROUND
  We examined the antiarrhythmic effects of vasostatin-1, a recently identified cardioregulatory peptide, in canine models of atrial fibrillation (AF).
  
  
  RESULTS
  In 13 pentobarbital-anesthetized dogs bilateral thoracotomies allowed the attachment of multielectrode catheters to superior and inferior pulmonary veins and atrial appendages (AA). Rapid atrial pacing (RAP) was maintained for 6 hours. Each hour, programmed stimulation was performed to determine the window of vulnerability (WOV), a measure of AF inducibility, at all sites. During the last 3 hours, vasostatin-1, 33 nM, was injected into the anterior right (AR) ganglionated plexus (GP) and inferior right (IR) GP every 30 minutes (n = 6). Seven dogs underwent 6 hours of RAP only (controls). At baseline, acetylcholine, 100 mM, was applied on the right AA and AF duration was recorded before and after injection of vasostatin-1, 33 nM, into the ARGP and IRGP. In separate experiments (n = 8), voltage-sinus rate response curves (surrogate for GP function) were constructed by applying high-frequency stimulation to the ARGP with incremental voltages with or without vasostatin-1. Vasostatin-1 significantly decreased the duration of acetylcholine-induced AF (11.0 ± 4.1 vs 5.5 ± 2.6 min, P = 0.02). The cumulative WOV (the sum of individual WOVs) significantly increased (P < 0.0001) during the first 3 hours and decreased toward baseline in the presence of vasostatin-1 (P < 0.0001). Cumulative WOV in controls steadily increased. Vasostatin-1 blunted the slowing of sinus rate with increasing stimulation voltage of ARGP.
  
  
  CONCLUSIONS
  Vasostatin-1 suppresses AF inducibility, likely by inhibiting GP function. These data may provide new insights into the role of peptide neuromodulators for AF therapy.
authors.affiliation: Heart Rhythm Institute, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104, USA.
authors.forename: Stavros
authors.initials: S
authors.lastname: Stavrakis
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Scherlag
authors.forename: Youqi
authors.initials: Y
authors.lastname: Fan
authors.forename: Yu
authors.initials: Y
authors.lastname: Liu
authors.forename: Qiming
authors.initials: Q
authors.lastname: Liu
authors.forename: Jun
authors.initials: J
authors.lastname: Mao
authors.forename: Heng
authors.initials: H
authors.lastname: Cai
authors.forename: Ralph
authors.initials: R
authors.lastname: Lazzara
authors.forename: Sunny S
authors.initials: SS
authors.lastname: Po
mesh_terms: D000109:Acetylcholine; D000200:Action Potentials; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001281:Atrial Fibrillation / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D002304:Cardiac Pacing, Artificial; D053379:Chromogranin A / Q000494:pharmacology*; D004195:Disease Models, Animal; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography; D022062:Electrophysiologic Techniques, Cardiac; D005725:Ganglia, Autonomic / Q000187:drug effects / Q000503:physiopathology; D006801:Humans; D008297:Male; D010446:Peptide Fragments / Q000494:pharmacology*; D012032:Refractory Period, Electrophysiological; D013997:Time Factors
chemical_list: D000889:Anti-Arrhythmia Agents; D053379:Chromogranin A; D010446:Peptide Fragments; C064110:vasostatin I; D000109:Acetylcholine