title: Effective suppression of atrial fibrillation by the antihistaminic agent antazoline: First experimental insights into a novel antiarrhythmic agent.
abstract: BACKGROUND
  The antihistaminic antazoline (ANT) was reported to be highly effective and safe for rapid conversion of atrial fibrillation (AF). We therefore analyzed underlying mechanisms in an experimental whole-heart model.
  
  
  RESULTS
  Isolated and retrogradely perfused rabbit hearts underwent a standardized protocol employing atrial burst pacing-induced AF in five of 20 hearts under baseline conditions (seven episodes). Thereafter, a combination of acetylcholine and isoproterenol was employed to enhance AF occurrence. Two monophasic action potential recordings on the left- and two on the right atrial epicardium showed a decrease in atrial action potential duration (aAPD, -25 msec, P<.05) and atrial effective refractory period (aERP; -52 msec, P<.01) after infusion of acetylcholine (1 μmol/L) and isoproterenol (1 μmol/L). This led to induction of AF in 14 of 20 hearts (145 episodes). Simultaneous infusion of ANT (20 μmol/L) led to a complete suppression of AF in all inducible hearts. Treatment with ANT also led to a significant increase in aAPD (+41 msec, P<.01) and aERP (+74 msec, P<.05), leading to a marked increase in atrial postrepolarization refractoriness (aPRR, +33 msec, P<.01). Results were compared to 13 rabbits treated with flecainide. Flecainide induced a significant increase in aPRR and resulted in induction of AF in seven of 13 hearts (51 episodes) while 11 of 13 hearts were inducible with acetylcholine and isoproterenol (93 episodes).
  
  
  CONCLUSIONS
  Administration of ANT was highly effective in suppressing AF. The antiarrhythmic effect could be explained by a significant increase in postrepolarization refractoriness as a result of a more marked increase in aERP as compared with aAPD.
authors.affiliation: Division of Clinical and Experimental Electrophysiology, Department of Cardiology and Angiology, University Hospital of Münster, Münster, Germany.
authors.forename: Gerrit
authors.initials: G
authors.lastname: Frommeyer
authors.affiliation: Division of Clinical and Experimental Electrophysiology, Department of Cardiology and Angiology, University Hospital of Münster, Münster, Germany.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Sterneberg
authors.affiliation: Division of Clinical and Experimental Electrophysiology, Department of Cardiology and Angiology, University Hospital of Münster, Münster, Germany.
authors.forename: Dirk G
authors.initials: DG
authors.lastname: Dechering
authors.affiliation: Division of Clinical and Experimental Electrophysiology, Department of Cardiology and Angiology, University Hospital of Münster, Münster, Germany.
authors.forename: Sven
authors.initials: S
authors.lastname: Kaese
authors.affiliation: Division of Clinical and Experimental Electrophysiology, Department of Cardiology and Angiology, University Hospital of Münster, Münster, Germany.
authors.forename: Nils
authors.initials: N
authors.lastname: Bögeholz
authors.affiliation: Division of Clinical and Experimental Electrophysiology, Department of Cardiology and Angiology, University Hospital of Münster, Münster, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Pott
authors.affiliation: Clinic of Exotic Pets, Reptiles, Exotic and Feral Birds, University of Hanover, Hanover, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Fehr
authors.affiliation: Märkische Kliniken GmbH, Department of Cardiology and Angiology, Klinikum Lüdenscheid, University of Witten-Herdecke, Witten, Germany.
authors.forename: Harilaos
authors.initials: H
authors.lastname: Bogossian
authors.affiliation: Division of Clinical and Experimental Electrophysiology, Department of Cardiology and Angiology, University Hospital of Münster, Münster, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Milberg
authors.affiliation: Division of Clinical and Experimental Electrophysiology, Department of Cardiology and Angiology, University Hospital of Münster, Münster, Germany.
authors.forename: Lars
authors.initials: L
authors.lastname: Eckardt
mesh_terms: D000109:Acetylcholine; D000200:Action Potentials; D000818:Animals; D000865:Antazoline / Q000494:pharmacology*; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001281:Atrial Fibrillation / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control*; D002304:Cardiac Pacing, Artificial; D004305:Dose-Response Relationship, Drug; D055808:Drug Discovery; D004562:Electrocardiography; D022062:Electrophysiologic Techniques, Cardiac; D005424:Flecainide / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects*; D006634:Histamine H1 Antagonists / Q000494:pharmacology*; D000067268:Isolated Heart Preparation; D007545:Isoproterenol; D011817:Rabbits; D012032:Refractory Period, Electrophysiological; D013997:Time Factors
chemical_list: D000889:Anti-Arrhythmia Agents; D006634:Histamine H1 Antagonists; D000865:Antazoline; D005424:Flecainide; D007545:Isoproterenol; D000109:Acetylcholine
keywords: Antazoline; Antiarrhythmic drugs; Atrial fibrillation; Flecainide; postrepolarization refractoriness