title: Pharmacological prevention and termination of focal atrial fibrillation.
abstract: OBJECTIVE
  Patients undergo ablation for focal atrial fibrillation (AF) as a result of failure of anti-arrhythmic drugs. Our basic studies have implicated cholinergic and adrenergic neurotransmitter release as the underlying mechanism for focal AF. Therefore, we tested the efficacy of a combination of sodium channel-blocking agents with additional vagolytic properties and a β-blocker to terminate and prevent focal AF.
  
  
  RESULTS
  In 18 Na-pentobarbital-anaesthetized dogs, after a right or left thoracotomy, acetylcholine (Ach, 0.5 cc, 100 mM) was injected into a fat pad containing ganglionated plexi (GP) or applied on an atrial appendage (AA) to induce focal firing at the pulmonary veins (PVs) or AA, respectively. Disopyramide (2-4 mg/kg, n= 6) or quinidine (3-6 mg/kg, n= 12) combined with esmolol or propranolol (1 mg/kg, n= 13 and 5, respectively) were slowly injected to terminate (Group I, n= 12) or prevent (Group II, n= 6) Ach-induced sustained focal AF. In another four dogs, only the sodium channel-blocking agents with additional vagolytic properties or only the β-blocker was injected prior to or after the initiation of focal AF. At baseline, the mean duration of AF induced by Ach was 26 ± 4 min. Group I: After drugs, Ach-induced AF duration was 3 ± 1 min (P< 0.001). Group II: Prior to drugs, Ach-induced AF lasted for 19 ± 3 min. With the drug combination the duration of Ach-induced AF, decreased to 6 ± 1/min, P< 0.001. Either quinidine or propranolol alone did not change the duration of Ach-induced AF, mean 25 ± 10 min compared with Ach alone, 28 ± 16 min, P= 0.2.
  
  
  CONCLUSIONS
  Type IA (cholinergic antagonist) plus Type II (β-adrenergic antagonist) provides significant prevention and suppression of focal AF arising at PV and non-PV sites.
authors.affiliation: Department of Cardiology, Cardiovascular Research Institute Maastricht, Maastricht University, Room 3.106, PO Box 616, 6200 MD Maastricht, The Netherlands.
authors.forename: Annerie M E
authors.initials: AM
authors.lastname: Moers
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Scherlag
authors.forename: Guodong
authors.initials: G
authors.lastname: Niu
authors.forename: Zhibing
authors.initials: Z
authors.lastname: Lu
authors.forename: Muhammad
authors.initials: M
authors.lastname: Ghias
authors.forename: Ralph
authors.initials: R
authors.lastname: Lazzara
authors.forename: Warren M
authors.initials: WM
authors.lastname: Jackman
authors.forename: Sunny S
authors.initials: SS
authors.lastname: Po
mesh_terms: D000109:Acetylcholine / Q000008:administration & dosage; D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000627:therapeutic use*; D020517:Atrial Appendage / Q000187:drug effects; D001281:Atrial Fibrillation / Q000188:drug therapy* / Q000517:prevention & control*; D004206:Disopyramide / Q000627:therapeutic use; D004285:Dogs; D004359:Drug Therapy, Combination; D011667:Pulmonary Veins / Q000187:drug effects; D011802:Quinidine / Q000627:therapeutic use; D026941:Sodium Channel Blockers / Q000627:therapeutic use
chemical_list: D000319:Adrenergic beta-Antagonists; D000889:Anti-Arrhythmia Agents; D026941:Sodium Channel Blockers; D004206:Disopyramide; D011802:Quinidine; D000109:Acetylcholine