Comparison of the effects on drug concentrations, electrophysiologic parameters, and termination of atrial fibrillation in dogs when procainamide and ibutilide are delivered into the right atrium versus intravenously

Andras Vereckei, Eduardo Warman, Rahul Mehra, Douglas P. Zipes

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Introduction: We tested the hypothesis that right intra-atrial (ia) administration of antiarrhythmic drugs resulted in higher peak serum drug concentrations, greater electrophysiologic effects, and greater efficacy for termination of atrial fibrillation (af) than intravenous (iv) drug delivery. Methods and Results: Eight dogs were treated with 9.7 mg/kg procainamide infusion and eight dogs with 0.02 mg/kg ibutilide infusion, injected over 5 minutes. Each dog had both an electrophysiologic (EP) and an AF termination study during IA and IV drug administration at ≥2-day intervals (total four studies each). Right atrial pacing capture threshold, right atrial effective refractory period (ERP), right atrial and right ventricular monophasic action potential (MAP) durations at 70% and 90% of repolarization (MAPD70, MAPD90), AH, HV, and QT intervals, QRS width, intra-arterial systolic and diastolic blood pressures, and cardiac output were measured at different time-points. Blood samples were drawn from the coronary sinus and femoral vein for drug level determination. The right atrium was paced at 400-msec cycle length throughout the study. AF was induced by rapid right atrial pacing and maintained by methacholine infusion at 1.5 to 3 μg/kg/min. The sustained AF was allowed to persist for 10 minutes before starting the antiarrhythmic drug infusion. We found no significant difference between the procainamide concentrations in the coronary sinus and femoral vein during IA and IV drug delivery. The time course and extent of increase in right atrial ERP, MAPD70, MAPD90, and all the other measured EP parameters did not differ between the two routes of drug administration. No significant difference was found in termination of AF between IV (5/7 procainamide; 4/8 ibutilide) or IA (3/8 procainamide; 3/8 ibutilide) drug delivery or between drugs (8/15 procainamide; 7/16 ibutilide). Conclusion: Our data do not support any beneficial effect of IA versus IV procainamide or ibutilide delivery.

Original languageEnglish
Pages (from-to)330-336
Number of pages7
JournalJournal of Cardiovascular Electrophysiology
Volume12
Issue number3
StatePublished - 2001

Fingerprint

Procainamide
Heart Atria
Atrial Fibrillation
Dogs
Pharmaceutical Preparations
Femoral Vein
Coronary Sinus
Anti-Arrhythmia Agents
Coronary Vessels
Drug Administration Routes
Blood Pressure
Methacholine Chloride
ibutilide
Cardiac Output
Action Potentials
Serum

Keywords

  • Atrial fibrillation
  • Ibutilide
  • Intravenous drug delivery
  • Procainamide
  • Right intra-atrial drug delivery

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology

Cite this

@article{634f501b70f24eb3a62a166e05f001d3,
title = "Comparison of the effects on drug concentrations, electrophysiologic parameters, and termination of atrial fibrillation in dogs when procainamide and ibutilide are delivered into the right atrium versus intravenously",
abstract = "Introduction: We tested the hypothesis that right intra-atrial (ia) administration of antiarrhythmic drugs resulted in higher peak serum drug concentrations, greater electrophysiologic effects, and greater efficacy for termination of atrial fibrillation (af) than intravenous (iv) drug delivery. Methods and Results: Eight dogs were treated with 9.7 mg/kg procainamide infusion and eight dogs with 0.02 mg/kg ibutilide infusion, injected over 5 minutes. Each dog had both an electrophysiologic (EP) and an AF termination study during IA and IV drug administration at ≥2-day intervals (total four studies each). Right atrial pacing capture threshold, right atrial effective refractory period (ERP), right atrial and right ventricular monophasic action potential (MAP) durations at 70{\%} and 90{\%} of repolarization (MAPD70, MAPD90), AH, HV, and QT intervals, QRS width, intra-arterial systolic and diastolic blood pressures, and cardiac output were measured at different time-points. Blood samples were drawn from the coronary sinus and femoral vein for drug level determination. The right atrium was paced at 400-msec cycle length throughout the study. AF was induced by rapid right atrial pacing and maintained by methacholine infusion at 1.5 to 3 μg/kg/min. The sustained AF was allowed to persist for 10 minutes before starting the antiarrhythmic drug infusion. We found no significant difference between the procainamide concentrations in the coronary sinus and femoral vein during IA and IV drug delivery. The time course and extent of increase in right atrial ERP, MAPD70, MAPD90, and all the other measured EP parameters did not differ between the two routes of drug administration. No significant difference was found in termination of AF between IV (5/7 procainamide; 4/8 ibutilide) or IA (3/8 procainamide; 3/8 ibutilide) drug delivery or between drugs (8/15 procainamide; 7/16 ibutilide). Conclusion: Our data do not support any beneficial effect of IA versus IV procainamide or ibutilide delivery.",
keywords = "Atrial fibrillation, Ibutilide, Intravenous drug delivery, Procainamide, Right intra-atrial drug delivery",
author = "Andras Vereckei and Eduardo Warman and Rahul Mehra and Zipes, {Douglas P.}",
year = "2001",
language = "English",
volume = "12",
pages = "330--336",
journal = "Journal of Cardiovascular Electrophysiology",
issn = "1045-3873",
publisher = "Wiley-Blackwell",
number = "3",

}

TY - JOUR

T1 - Comparison of the effects on drug concentrations, electrophysiologic parameters, and termination of atrial fibrillation in dogs when procainamide and ibutilide are delivered into the right atrium versus intravenously

AU - Vereckei, Andras

AU - Warman, Eduardo

AU - Mehra, Rahul

AU - Zipes, Douglas P.

PY - 2001

Y1 - 2001

N2 - Introduction: We tested the hypothesis that right intra-atrial (ia) administration of antiarrhythmic drugs resulted in higher peak serum drug concentrations, greater electrophysiologic effects, and greater efficacy for termination of atrial fibrillation (af) than intravenous (iv) drug delivery. Methods and Results: Eight dogs were treated with 9.7 mg/kg procainamide infusion and eight dogs with 0.02 mg/kg ibutilide infusion, injected over 5 minutes. Each dog had both an electrophysiologic (EP) and an AF termination study during IA and IV drug administration at ≥2-day intervals (total four studies each). Right atrial pacing capture threshold, right atrial effective refractory period (ERP), right atrial and right ventricular monophasic action potential (MAP) durations at 70% and 90% of repolarization (MAPD70, MAPD90), AH, HV, and QT intervals, QRS width, intra-arterial systolic and diastolic blood pressures, and cardiac output were measured at different time-points. Blood samples were drawn from the coronary sinus and femoral vein for drug level determination. The right atrium was paced at 400-msec cycle length throughout the study. AF was induced by rapid right atrial pacing and maintained by methacholine infusion at 1.5 to 3 μg/kg/min. The sustained AF was allowed to persist for 10 minutes before starting the antiarrhythmic drug infusion. We found no significant difference between the procainamide concentrations in the coronary sinus and femoral vein during IA and IV drug delivery. The time course and extent of increase in right atrial ERP, MAPD70, MAPD90, and all the other measured EP parameters did not differ between the two routes of drug administration. No significant difference was found in termination of AF between IV (5/7 procainamide; 4/8 ibutilide) or IA (3/8 procainamide; 3/8 ibutilide) drug delivery or between drugs (8/15 procainamide; 7/16 ibutilide). Conclusion: Our data do not support any beneficial effect of IA versus IV procainamide or ibutilide delivery.

AB - Introduction: We tested the hypothesis that right intra-atrial (ia) administration of antiarrhythmic drugs resulted in higher peak serum drug concentrations, greater electrophysiologic effects, and greater efficacy for termination of atrial fibrillation (af) than intravenous (iv) drug delivery. Methods and Results: Eight dogs were treated with 9.7 mg/kg procainamide infusion and eight dogs with 0.02 mg/kg ibutilide infusion, injected over 5 minutes. Each dog had both an electrophysiologic (EP) and an AF termination study during IA and IV drug administration at ≥2-day intervals (total four studies each). Right atrial pacing capture threshold, right atrial effective refractory period (ERP), right atrial and right ventricular monophasic action potential (MAP) durations at 70% and 90% of repolarization (MAPD70, MAPD90), AH, HV, and QT intervals, QRS width, intra-arterial systolic and diastolic blood pressures, and cardiac output were measured at different time-points. Blood samples were drawn from the coronary sinus and femoral vein for drug level determination. The right atrium was paced at 400-msec cycle length throughout the study. AF was induced by rapid right atrial pacing and maintained by methacholine infusion at 1.5 to 3 μg/kg/min. The sustained AF was allowed to persist for 10 minutes before starting the antiarrhythmic drug infusion. We found no significant difference between the procainamide concentrations in the coronary sinus and femoral vein during IA and IV drug delivery. The time course and extent of increase in right atrial ERP, MAPD70, MAPD90, and all the other measured EP parameters did not differ between the two routes of drug administration. No significant difference was found in termination of AF between IV (5/7 procainamide; 4/8 ibutilide) or IA (3/8 procainamide; 3/8 ibutilide) drug delivery or between drugs (8/15 procainamide; 7/16 ibutilide). Conclusion: Our data do not support any beneficial effect of IA versus IV procainamide or ibutilide delivery.

KW - Atrial fibrillation

KW - Ibutilide

KW - Intravenous drug delivery

KW - Procainamide

KW - Right intra-atrial drug delivery

UR - http://www.scopus.com/inward/record.url?scp=0035103521&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035103521&partnerID=8YFLogxK

M3 - Article

C2 - 11291807

AN - SCOPUS:0035103521

VL - 12

SP - 330

EP - 336

JO - Journal of Cardiovascular Electrophysiology

JF - Journal of Cardiovascular Electrophysiology

SN - 1045-3873

IS - 3

ER -