title: Intrapericardial ibutilide administration fails to terminate pacing-induced sustained atrial fibrillation in dogs.
abstract: OBJECTIVE
  The hypothesis that intrapericardial (ip.) ibutilide administration would terminate pacing-induced sustained atrial fibrillation (AF) and ibutilide distribution were tested.
  
  
  RESULTS
  Sustained (> or =24 hours) AF was induced by 59 +/- 20 day rapid atrial pacing in 19 dogs. After sustained AF was present, the atrial pacemaker was turned off and 9 open chest dogs received 0.015 mg/kg ibutilide (37 degrees C) in 30 ml saline into the pericardial sac. Ten control dogs received 30 ml saline (37 degrees C) ip. QT intervals, right ventricular monophasic action potential duration at 90% of repolarization (RV-MAPD(90)), AF mean cycle length (AFCL(m)), systolic- and diastolic intraarterial blood pressures, intrapericardial-, right atrial- and ventricular pressures, cardiac output and ibutilide concentrations were measured. If AF persisted after the 1st drug infusion, dual site rapid atrial pacing (DRAP) simultaneously from the high right atrium and coronary sinus was performed to terminate AF. If it was ineffective, a 2nd ip. drug infusion in the same fashion as the 1st one, was attempted. There was no significant difference in AF termination [5/9 (56%) in ibutilide treated and 3/10 (30%) in control dogs] between the two groups. DRAP never terminated AF. The AF duration did not differ between the two groups. Compared with control, ibutilide treatment prolonged significantly AFCL(m) (p < 0.001) and non-significantly QT, RV-MAPD(90). No significant difference was found in systolic and diastolic blood pressure and cardiac output between the two groups. The two orders of magnitude greater ibutilide concentration in the pericardial fluid than that in the femoral vein decreased rapidly over time, drug concentration was greatest in the atria, smaller in the ventricular myocardium, with a trend decreasing from the epi- to endocardium.
  
  
  CONCLUSIONS
  Despite a significant atrial electrophysiological effect, ip. delivery of ibutilide did not result in higher AF termination rate compared with control.
authors.affiliation: 3rd Department of Medicine, Semmelweis University, School of Medicine, Budapest, Kútvölgyi út 4, Hungary 1125. vereckei@kut.sote.hu
authors.forename: András
authors.initials: A
authors.lastname: Vereckei
authors.forename: J Cristopher
authors.initials: JC
authors.lastname: Gorski
authors.forename: Michael
authors.initials: M
authors.lastname: Ujhelyi
authors.forename: Rahul
authors.initials: R
authors.lastname: Mehra
authors.forename: Douglas P
authors.initials: DP
authors.lastname: Zipes
mesh_terms: D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001281:Atrial Fibrillation / Q000188:drug therapy*; D004195:Disease Models, Animal; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography; D022062:Electrophysiologic Techniques, Cardiac; D005260:Female; D006325:Heart Atria / Q000187:drug effects; D007322:Instillation, Drug; D008297:Male; D010496:Pericardium; D013449:Sulfonamides / Q000008:administration & dosage / Q000494:pharmacology*; D013997:Time Factors; D017211:Treatment Failure
chemical_list: D000889:Anti-Arrhythmia Agents; D013449:Sulfonamides; C067192:ibutilide