title: Effects of intrapericardial sotalol and flecainide on transmural atrial electrophysiology and atrial fibrillation.
abstract: BACKGROUND
  Intrapericardial (IPC) delivery of antiarrhythmic agents is an appealing idea to increase the therapeutic width and reduce side effects of drugs, particularly in the thin atria. The aim of this study was to determine the effects of IPC versus intravenous (IV) d,l-sotalol and flecainide infusion on transmural atrial electrophysiology and sustained atrial fibrillation (AF) in the goat.
  
  
  RESULTS
  Effects of IPC and IV sotalol and flecainide infusion on epi- and endocardial atrial electrophysiology, ECG, and tissue drug concentrations were studied in goats without and with persistent AF (>24 hours). Epicardial atrial refractory period (AERP, bcl 400 ms) increased after 120 minutes of 1 mg/kg/hour IPC sotalol with 61 +/- 8 ms (P = 0.02), whereas the endocardial AERP was not affected. One mg/kg/hour IPC flecainide increased the epicardial pacing threshold and the epicardial AERP with 4 +/- 0.5 mA (P = 0.003) and 33 +/- 11 ms (P = 0.05), respectively. Endocardial values were unchanged. Marked ST-elevations in the precordial ECG leads were observed after IPC flecainide. In the AF group, IPC drugs did not prolong AF cycle length to a greater extent than IV delivery. The number of cardioversions was not different between the two delivery routes. A steep transmural drug concentration gradient after IPC sotalol and flecainide was observed in all heart chambers.
  
  
  CONCLUSIONS
  IPC sotalol and flecainide infusion in goats markedly affects epicardial atrial electrophysiology. IPC delivery, however, does not prolong AFCL or terminate AF to a greater extent than IV infusion. This suggests that the perpetuation of AF is not dominated by the epicardial and sub epicardial atrial layers.
authors.affiliation: Cardiovascular Research Institute Maastricht, Department of Cardiothoracic Surgery, Masstricht, The Netherlands. T.vanBrakel@thorax.umcn.nl
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: van Brakel
authors.forename: J J Rob
authors.initials: JJ
authors.lastname: Hermans
authors.forename: Ryan E
authors.initials: RE
authors.lastname: Accord
authors.forename: Ulrich
authors.initials: U
authors.lastname: Schotten
authors.forename: Jos F M
authors.initials: JF
authors.lastname: Smits
authors.forename: Maurits A
authors.initials: MA
authors.lastname: Allessie
authors.forename: Jos G
authors.initials: JG
authors.lastname: Maessen
mesh_terms: D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D001281:Atrial Fibrillation / Q000188:drug therapy* / Q000503:physiopathology; D004558:Electric Stimulation; D004562:Electrocardiography; D004594:Electrophysiology; D005424:Flecainide / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D006041:Goats / Q000502:physiology*; D006325:Heart Atria; D007267:Injections; D007275:Injections, Intravenous; D010496:Pericardium / Q000503:physiopathology; D013015:Sotalol / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*
chemical_list: D000889:Anti-Arrhythmia Agents; D013015:Sotalol; D005424:Flecainide