title: A randomized invasive cardiac electrophysiology study of the combined ion channel blocker AZD1305 in patients after catheter ablation of atrial flutter.
abstract: BACKGROUND
  This study assessed the cardiac electrophysiological and hemodynamic effects of an intravenous infusion of the combined ion channel blocker AZD1305.
  
  
  METHODS
  After successful ablation of atrial flutter, patients were randomized to receive placebo (n = 12) or AZD1305 (n = 38) in 4 ascending dose groups. Electrophysiological and hemodynamic measurements were performed before and commencing 20 minutes after start of infusion.
  
  
  RESULTS
  Left atrial effective refractory period increased dose and the primary outcome measure increased dose and plasma concentration dependently, with a mean increase of 55 milliseconds in dose group 3. There was a corresponding increase in right atrial effective refractory period of 84 milliseconds. The right ventricular effective refractory period and the paced QT interval also increased dose and concentration dependently, by 59 and 70 milliseconds, respectively, in dose group 3. There were indications of moderate increases of atrial, atrioventricular nodal, and ventricular conduction times. No consistent changes in intracardiac pressures were observed, but there was a small transient decrease in systolic blood pressure. Adverse events were consistent with the study population and procedure, and there were no signs of proarrhythmia despite marked delay in ventricular repolarization in some individuals.
  
  
  CONCLUSIONS
  AZD1305 shows electrophysiological characteristics indicative of potential antiarrhythmic efficacy in atrial fibrillation.
authors.affiliation: Department of Cardiology, University Central Hospital, Helsinki, Finland.
authors.forename: Lauri
authors.initials: L
authors.lastname: Toivonen
authors.forename: Pekka
authors.initials: P
authors.lastname: Raatikainen
authors.forename: Håkan
authors.initials: H
authors.lastname: Walfridsson
authors.forename: Anders
authors.initials: A
authors.lastname: Englund
authors.forename: Finn
authors.initials: F
authors.lastname: Hegbom
authors.forename: Ole-Gunnar
authors.initials: OG
authors.lastname: Anfinsen
authors.forename: Knut
authors.initials: K
authors.lastname: Gjesdal
authors.forename: Steen
authors.initials: S
authors.lastname: Pehrson
authors.forename: Susanne
authors.initials: S
authors.lastname: Johansson
authors.forename: Lars
authors.initials: L
authors.lastname: Frison
authors.forename: Anders R
authors.initials: AR
authors.lastname: Berggren
authors.forename: Nils
authors.initials: N
authors.lastname: Edvardsson
mesh_terms: D000328:Adult; D000368:Aged; D001282:Atrial Flutter / Q000601:surgery*; D053961:Azabicyclo Compounds / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D002219:Carbamates / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D017115:Catheter Ablation; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004562:Electrocardiography; D022062:Electrophysiologic Techniques, Cardiac; D005260:Female; D006329:Heart Conduction System / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D012032:Refractory Period, Electrophysiological / Q000187:drug effects; D026941:Sodium Channel Blockers / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*
chemical_list: D053961:Azabicyclo Compounds; D002121:Calcium Channel Blockers; D002219:Carbamates; D026941:Sodium Channel Blockers; C550721:tert-butyl (2-(7-(2-(4-cyano-2-fluorophenoxy)ethyl)-9-oxa-3,7-diazabicyclo(3.3.1)non3-yl)ethyl)carbamate