title: Electrical remodeling due to atrial fibrillation in chronically instrumented conscious goats: roles of neurohumoral changes, ischemia, atrial stretch, and high rate of electrical activation.
abstract: BACKGROUND
  Recently, we developed a goat model of chronic atrial fibrillation (AF). Due to AF, the atrial effective refractory period (AERP) shortened and its physiological rate adaptation inversed, whereas the rate and stability of AF increased. The goal of the present study was to evaluate the role of (1) the autonomic nervous system, (2) ischemia, (3) stretch, (4) atrial natriuretic factor (ANF), and (5) rapid atrial pacing in this process of electrical remodeling.
  
  
  RESULTS
  Twenty-five goats were chronically instrumented with multiple epicardial atrial electrodes. Infusion of atropine (1.0 mg/kg; n=6) or propranolol (0.6 mg/kg; n=6) did not abolish the AF-induced shortening of AERP or interval (AFI). Blockade of K+(ATP) channels by glibenclamide (10 micromol/kg; n=6) slightly increased the AFI from 95+/-4 to 101+/-5 ms, but AFI remained considerably shorter than during acute AF (145 ms). Glibenclamide had no significant effect on AERP after electrical cardioversion of AF (69+/-14 versus 75+/-15 ms). Volume loading by 0.5 to 1.0 L of Hemaccel (n=12) did not shorten AERP. The median plasma level of ANF increased from 42 to 99 pg/mL after 1 to 4 weeks of AF (n=6), but ANF infusion (0.1 to 3.1 microg/min, n=4) did not shorten AERP. Rapid atrial pacing (24 to 48 hours; n=10) progressively shortened AERP from 134+/-10 to 105+/-6 ms and inversed its physiological rate adaptation.
  
  
  CONCLUSIONS
  Electrical remodeling by AF is not mediated by changes in autonomic tone, ischemia, stretch, or ANF. The high rate of electrical activation itself provides the stimulus for the AF-induced changes in AERP.
authors.affiliation: Department of Physiology, Cardiovascular Research Institute Maastricht, Maastricht University, The Netherlands.
authors.forename: M C
authors.initials: MC
authors.lastname: Wijffels
authors.forename: C J
authors.initials: CJ
authors.lastname: Kirchhof
authors.forename: R
authors.initials: R
authors.lastname: Dorland
authors.forename: J
authors.initials: J
authors.lastname: Power
authors.forename: M A
authors.initials: MA
authors.lastname: Allessie
mesh_terms: D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D001281:Atrial Fibrillation / Q000503:physiopathology*; D016275:Atrial Function / Q000502:physiology*; D009320:Atrial Natriuretic Factor / Q000494:pharmacology; D001285:Atropine / Q000494:pharmacology; D002304:Cardiac Pacing, Artificial / Q000379:methods; D004106:Dilatation; D004594:Electrophysiology; D005905:Glyburide / Q000494:pharmacology; D006041:Goats; D006321:Heart / Q000187:drug effects / Q000503:physiopathology*; D017202:Myocardial Ischemia / Q000503:physiopathology; D018377:Neurotransmitter Agents / Q000378:metabolism*; D010812:Physical Stimulation; D011433:Propranolol / Q000494:pharmacology; D012032:Refractory Period, Electrophysiological / Q000187:drug effects
chemical_list: D000889:Anti-Arrhythmia Agents; D018377:Neurotransmitter Agents; D001285:Atropine; D009320:Atrial Natriuretic Factor; D011433:Propranolol; D005905:Glyburide