title: Potent antiarrhythmic effects of chronic amiodarone in canine pulmonary vein sleeve preparations.
abstract: OBJECTIVE
  To examine the effects of chronic amiodarone on the electrophysiology of canine pulmonary vein (PV) sleeve preparations and left ventricular wedge preparation.
  
  
  BACKGROUND
  Amiodarone is commonly used for the treatment of ventricular and supraventricular arrhythmias. Ectopic activity arising from the PV plays a prominent role in the development of atrial fibrillation (AF).
  
  
  METHODS
  Standard microelectrode techniques were used to evaluate the electrophysiological characteristics of superfused PV sleeve (left superior or inferior) and arterially perfused left ventricular (LV) wedge preparations isolated from untreated and chronic amiodarone-treated dogs (amiodarone, 40 mg/kg daily for 6 weeks).
  
  
  RESULTS
  In PV sleeves, chronic amiodarone (n = 6) induced a significant increase in action potential duration at 90% repolarization (APD90) and a significant use-dependent reduction in Vmax leading to 1:1 activation failure at long cycle lengths (basic cycle length of 124 +/- 15 ms in control vs 420 +/- 320 ms after chronic amiodarone [P < 0.01]). Diastolic threshold of excitation increased from 0.3 +/- 0.2 to 1.8 +/- 0.7 mA (P < 0.01). Delayed and late phase 3 early afterdepolarizations and triggered activity could be induced in PV sleeve preparations using acetylcholine (ACh, 1 microM), high calcium ([Ca2+]o = 5.4 mM), isoproterenol (Iso, 1 microM), or their combination in 6 of 6 untreated PV sleeves, but in only 1 of 5 chronic amiodarone-treated PV sleeve preparations. Vmax, conduction velocity, and 1:1 activation failure were much more affected in PV sleeves versus LV wedge preparations isolated from amiodarone-treated animals.
  
  
  CONCLUSIONS
  The results point to potent effects of chronic amiodarone to preferentially suppress arrhythmogenic substrates and triggers arising from the PV sleeves of the dog.
authors.affiliation: Masonic Medical Research Laboratory, Utica, New York 13501, USA.
authors.forename: Serge
authors.initials: S
authors.lastname: Sicouri
authors.forename: Luiz
authors.initials: L
authors.lastname: Belardinelli
authors.forename: Leif
authors.initials: L
authors.lastname: Carlsson
authors.forename: Charles
authors.initials: C
authors.lastname: Antzelevitch
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000200:Action Potentials; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000638:Amiodarone / Q000494:pharmacology*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001281:Atrial Fibrillation / Q000188:drug therapy* / Q000503:physiopathology; D002118:Calcium / Q000378:metabolism; D002304:Cardiac Pacing, Artificial; D018678:Cholinergic Agents / Q000494:pharmacology; D004285:Dogs; D022062:Electrophysiologic Techniques, Cardiac; D006329:Heart Conduction System / Q000187:drug effects* / Q000503:physiopathology; D006352:Heart Ventricles / Q000187:drug effects; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008839:Microelectrodes; D010477:Perfusion; D011667:Pulmonary Veins / Q000187:drug effects* / Q000503:physiopathology; D013997:Time Factors
chemical_list: D000318:Adrenergic beta-Agonists; D000889:Anti-Arrhythmia Agents; D018678:Cholinergic Agents; D007545:Isoproterenol; D000638:Amiodarone; D000109:Acetylcholine; D002118:Calcium