Intrapericardial ibutilide administration fails to terminate pacing-induced sustained atrial fibrillation in dogs

András Vereckei, J. Cristopher Gorski, Michael Ujhelyi, Rahul Mehra, Douglas P. Zipes

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Purpose: The hypothesis that intrapericardial (ip.) ibutilide administration would terminate pacing-induced sustained atrial fibrillation (AF) and ibutilide distribution were tested. Methods and results: Sustained (≥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°C) in 30 ml saline into the pericardial sac. Ten control dogs received 30 ml saline (37°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.

Original languageEnglish
Pages (from-to)269-277
Number of pages9
JournalCardiovascular Drugs and Therapy
Volume18
Issue number4
DOIs
StatePublished - Jul 2004

Fingerprint

Atrial Fibrillation
Dogs
Blood Pressure
Cardiac Output
Action Potentials
ibutilide
Pharmaceutical Preparations
Endocardium
Atrial Pressure
Femoral Vein
Coronary Sinus
Pericardium
Ventricular Pressure
Heart Atria
Myocardium
Thorax

Keywords

  • atrial fibrillation
  • ibutilide
  • intrapericardial administration

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Cardiology and Cardiovascular Medicine
  • Pharmacology

Cite this

Intrapericardial ibutilide administration fails to terminate pacing-induced sustained atrial fibrillation in dogs. / Vereckei, András; Gorski, J. Cristopher; Ujhelyi, Michael; Mehra, Rahul; Zipes, Douglas P.

In: Cardiovascular Drugs and Therapy, Vol. 18, No. 4, 07.2004, p. 269-277.

Research output: Contribution to journalArticle

Vereckei, András ; Gorski, J. Cristopher ; Ujhelyi, Michael ; Mehra, Rahul ; Zipes, Douglas P. / Intrapericardial ibutilide administration fails to terminate pacing-induced sustained atrial fibrillation in dogs. In: Cardiovascular Drugs and Therapy. 2004 ; Vol. 18, No. 4. pp. 269-277.
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AU - Mehra, Rahul

AU - Zipes, Douglas P.

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N2 - Purpose: The hypothesis that intrapericardial (ip.) ibutilide administration would terminate pacing-induced sustained atrial fibrillation (AF) and ibutilide distribution were tested. Methods and results: Sustained (≥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°C) in 30 ml saline into the pericardial sac. Ten control dogs received 30 ml saline (37°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.

AB - Purpose: The hypothesis that intrapericardial (ip.) ibutilide administration would terminate pacing-induced sustained atrial fibrillation (AF) and ibutilide distribution were tested. Methods and results: Sustained (≥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°C) in 30 ml saline into the pericardial sac. Ten control dogs received 30 ml saline (37°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.

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