title: Amiodarone instilled into the canine pericardial sac migrates transmurally to produce electrophysiologic effects and suppress atrial fibrillation.
abstract: BACKGROUND
  We investigated whether amiodarone delivered into the pericardial sac exerted an effect on atrial and ventricular refractoriness, impulse generation, and conduction and on induced atrial fibrillation.
  
  
  RESULTS
  All animals were anesthetized with alpha-chloralose. After a sternotomy, the pericardium was opened and cradled to produce a "container" of approximately 75 mL. Part I experimental animals received amiodarone, 0.5, 1.0, or 5.0 mg/mL, dissolved in 3 mL polysorbate 80 and 5% dextrose in water (D5W) instilled into their pericardial sac for 3-hour intervals. Part II experimental animals received either 1.0 or 5.0 mg/mL of amiodarone. Control dogs received a pericardial solution of 3 mL polysorbate 80 in D5W. Pre- and postinstillation electrophysiologic studies were performed. In part I, the increase in sinus cycle length, 1:1 AV conduction, and effective refractory period (ERP) of atrium, right ventricular (RV) and left ventricular epicardium, and RV endocardium were significantly greater in animals receiving amiodarone compared with controls. Amiodarone concentrations in the tissue samples were highest in the superficial sites of the atria, sinoatrial node, and ventricular epicardial samples and lowest in the interventricular septum. Only trace concentrations of amiodarone and no desethylamiodarone were found in the blood samples. In part II, atrial ERP significantly increased in the animals receiving amiodarone, and the number of episodes of sustained atrial fibrillation that could be induced decreased.
  
  
  CONCLUSIONS
  Amiodarone instilled into the pericardial sac migrates transmurally to produce significant electrophysiologic effects at superficial sites and appears to suppress electrically induced atrial fibrillation.
authors.affiliation: Krannert Institute of Cardiology, Indianapolis, Indiana, USA.
authors.forename: G M
authors.initials: GM
authors.lastname: Ayers
authors.forename: T H
authors.initials: TH
authors.lastname: Rho
authors.forename: J
authors.initials: J
authors.lastname: Ben-David
authors.forename: H R
authors.initials: HR
authors.lastname: Besch
authors.forename: D P
authors.initials: DP
authors.lastname: Zipes
mesh_terms: D000638:Amiodarone / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage*; D001281:Atrial Fibrillation / Q000188:drug therapy*; D004285:Dogs; D005260:Female; D006329:Heart Conduction System / Q000187:drug effects* / Q000502:physiology; D008297:Male; D010496:Pericardium / Q000378:metabolism; D012032:Refractory Period, Electrophysiological / Q000187:drug effects
chemical_list: D000889:Anti-Arrhythmia Agents; D000638:Amiodarone