title: Electrophysiological and antiarrhythmic effects of the novel antiarrhythmic agent AZD7009: a comparison with azimilide and AVE0118 in the acutely dilated right atrium of the rabbit in vitro.
abstract: OBJECTIVE
  To compare the electrophysiological and antiarrhythmic effects of AZD7009, azimilide, and AVE0118 in the acutely dilated rabbit atria in vitro.
  
  
  RESULTS
  In the isolated Langendorf-perfused rabbit heart, the atrial effective refractory period (AERP) and the inducibility of atrial fibrillation (AF) were measured at increasing concentrations of AZD7009 (0.1-3 microM), azimilide (0.1-3 microM), and AVE0118 (0.3-10 microM). In separate groups of atria, termination of sustained AF was assessed. In non-dilated atria, the AERP was 82+/-1.3 ms (mean+/-SEM) and AF could not be induced. Dilation significantly reduced the AERP to 49+/-1.0 ms (P<0.001) and 92% of the atria became inducible. Perfusion with AZD7009, azimilide, and AVE0118 concentration-dependently increased the AERP and reduced the AF inducibility. At the highest concentrations of AZD7009, azimilide, and AVE0118, AERP and AF inducibility changed from 50+/-4.5 to 136+/-6.6 ms and 80 to 0% (both P<0.001) from 51+/-3.0 to 105+/-9.9 ms (P<0.001) and 80 to 0% (P<0.01) and from 46+/-2.8 to 85+/-6.0 ms and 90 to 0% (both P<0.001). Restoration of sinus rhythm was seen in 6/6, 5/6, and 5/6 hearts perfused with AZD7009, azimilide, and AVE0118, respectively.
  
  
  CONCLUSIONS
  In the dilated rabbit atria, AZD7009, azimilide, and AVE0118 concentration-dependently increased AERP, effectively prevented AF induction, and rapidly restored sinus rhythm.
authors.affiliation: AstraZeneca R&D Mölndal, Integrative Pharmacology, Pepparedsleden 1, S-431 83 Mölndal, Sweden.
authors.forename: Lena
authors.initials: L
authors.lastname: Löfberg
authors.forename: Ingemar
authors.initials: I
authors.lastname: Jacobson
authors.forename: Leif
authors.initials: L
authors.lastname: Carlsson
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001145:Arrhythmias, Cardiac / Q000188:drug therapy*; D001713:Biphenyl Compounds / Q000494:pharmacology*; D004108:Dilatation, Pathologic; D006325:Heart Atria / Q000187:drug effects*; D006827:Hydantoins; D048289:Imidazolidines / Q000494:pharmacology*; D066298:In Vitro Techniques; D009930:Organic Chemicals / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology*; D011817:Rabbits
chemical_list: C501729:AVE 0118; C514242:AZD 7009; D000889:Anti-Arrhythmia Agents; D001713:Biphenyl Compounds; D006827:Hydantoins; D048289:Imidazolidines; D009930:Organic Chemicals; D010879:Piperazines; C086123:azimilide