Proarrhythmic effects of intravenous quinidine, amiodarone, d-sotalol, and almokalant in the anesthetized rabbit model of torsade de pointes

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

The proarrhythmic effects of four antiarrhythmic agents were examined during α1-adrenoceptor stimulation in chloralose-anesthetized rabbits. Each dose of almokalant (26, 88, and 260 μg/kg), D-sotalol, quinidine, or amiodarone (each 3, 10, and 30 mg/kg) was infused i.v. over 5 min and there was a 20-min interval between each infusion. D-sotalol and almokalant evoked torsade de pointes (TdP) and other arrhythmics, frequently. The incidences of TdP were 0, 50, and 40% after administering the first, second, and third doses of the nonselective IKr inhibitor D-sotalol, respectively. Similarly, these values were 20, 40, and 33% after administering the first, second, and third doses, respectively, of the selective IKr inhibitor almokalant. Quinidine elicited only a few arrhythmics, but not TdP. Quinidine, D-sotalol, and almokalant evoked conduction blocks in a dose-related manner (p <0.05) and prolonged QT and QTc intervals (p <0.05). Amiodarone neither prolonged QT and QTc nor evoked ventricular tachyarrhythmias, blocks, or other proarrhythmias. In conclusion, these results show no direct correlation between the occurrence of TdP and the infusion rate or dose of anti-arrhythmics. Furthermore, the lack of TdP with quinidine warns of false-negative results in the applied model.

Original languageEnglish
Pages (from-to)287-297
Number of pages11
JournalJournal of Cardiovascular Pharmacology
Volume39
Issue number2
DOIs
Publication statusPublished - 2002

Fingerprint

Sotalol
Torsades de Pointes
Quinidine
Amiodarone
Rabbits
Chloralose
Anti-Arrhythmia Agents
Tachycardia
Adrenergic Receptors
almokalant
Incidence

Keywords

  • α-Adrenoceptor stimulation
  • Almokalant
  • Amiodarone
  • D-sotalol
  • Quinidine
  • Torsade de pointes

ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine

Cite this

@article{8f434353b048473e89e99d95e7eca463,
title = "Proarrhythmic effects of intravenous quinidine, amiodarone, d-sotalol, and almokalant in the anesthetized rabbit model of torsade de pointes",
abstract = "The proarrhythmic effects of four antiarrhythmic agents were examined during α1-adrenoceptor stimulation in chloralose-anesthetized rabbits. Each dose of almokalant (26, 88, and 260 μg/kg), D-sotalol, quinidine, or amiodarone (each 3, 10, and 30 mg/kg) was infused i.v. over 5 min and there was a 20-min interval between each infusion. D-sotalol and almokalant evoked torsade de pointes (TdP) and other arrhythmics, frequently. The incidences of TdP were 0, 50, and 40{\%} after administering the first, second, and third doses of the nonselective IKr inhibitor D-sotalol, respectively. Similarly, these values were 20, 40, and 33{\%} after administering the first, second, and third doses, respectively, of the selective IKr inhibitor almokalant. Quinidine elicited only a few arrhythmics, but not TdP. Quinidine, D-sotalol, and almokalant evoked conduction blocks in a dose-related manner (p <0.05) and prolonged QT and QTc intervals (p <0.05). Amiodarone neither prolonged QT and QTc nor evoked ventricular tachyarrhythmias, blocks, or other proarrhythmias. In conclusion, these results show no direct correlation between the occurrence of TdP and the infusion rate or dose of anti-arrhythmics. Furthermore, the lack of TdP with quinidine warns of false-negative results in the applied model.",
keywords = "α-Adrenoceptor stimulation, Almokalant, Amiodarone, D-sotalol, Quinidine, Torsade de pointes",
author = "A. Farkas and I. Lepr{\'a}n and J. Papp",
year = "2002",
doi = "10.1097/00005344-200202000-00016",
language = "English",
volume = "39",
pages = "287--297",
journal = "Journal of Cardiovascular Pharmacology",
issn = "0160-2446",
publisher = "Lippincott Williams and Wilkins",
number = "2",

}

TY - JOUR

T1 - Proarrhythmic effects of intravenous quinidine, amiodarone, d-sotalol, and almokalant in the anesthetized rabbit model of torsade de pointes

AU - Farkas, A.

AU - Leprán, I.

AU - Papp, J.

PY - 2002

Y1 - 2002

N2 - The proarrhythmic effects of four antiarrhythmic agents were examined during α1-adrenoceptor stimulation in chloralose-anesthetized rabbits. Each dose of almokalant (26, 88, and 260 μg/kg), D-sotalol, quinidine, or amiodarone (each 3, 10, and 30 mg/kg) was infused i.v. over 5 min and there was a 20-min interval between each infusion. D-sotalol and almokalant evoked torsade de pointes (TdP) and other arrhythmics, frequently. The incidences of TdP were 0, 50, and 40% after administering the first, second, and third doses of the nonselective IKr inhibitor D-sotalol, respectively. Similarly, these values were 20, 40, and 33% after administering the first, second, and third doses, respectively, of the selective IKr inhibitor almokalant. Quinidine elicited only a few arrhythmics, but not TdP. Quinidine, D-sotalol, and almokalant evoked conduction blocks in a dose-related manner (p <0.05) and prolonged QT and QTc intervals (p <0.05). Amiodarone neither prolonged QT and QTc nor evoked ventricular tachyarrhythmias, blocks, or other proarrhythmias. In conclusion, these results show no direct correlation between the occurrence of TdP and the infusion rate or dose of anti-arrhythmics. Furthermore, the lack of TdP with quinidine warns of false-negative results in the applied model.

AB - The proarrhythmic effects of four antiarrhythmic agents were examined during α1-adrenoceptor stimulation in chloralose-anesthetized rabbits. Each dose of almokalant (26, 88, and 260 μg/kg), D-sotalol, quinidine, or amiodarone (each 3, 10, and 30 mg/kg) was infused i.v. over 5 min and there was a 20-min interval between each infusion. D-sotalol and almokalant evoked torsade de pointes (TdP) and other arrhythmics, frequently. The incidences of TdP were 0, 50, and 40% after administering the first, second, and third doses of the nonselective IKr inhibitor D-sotalol, respectively. Similarly, these values were 20, 40, and 33% after administering the first, second, and third doses, respectively, of the selective IKr inhibitor almokalant. Quinidine elicited only a few arrhythmics, but not TdP. Quinidine, D-sotalol, and almokalant evoked conduction blocks in a dose-related manner (p <0.05) and prolonged QT and QTc intervals (p <0.05). Amiodarone neither prolonged QT and QTc nor evoked ventricular tachyarrhythmias, blocks, or other proarrhythmias. In conclusion, these results show no direct correlation between the occurrence of TdP and the infusion rate or dose of anti-arrhythmics. Furthermore, the lack of TdP with quinidine warns of false-negative results in the applied model.

KW - α-Adrenoceptor stimulation

KW - Almokalant

KW - Amiodarone

KW - D-sotalol

KW - Quinidine

KW - Torsade de pointes

UR - http://www.scopus.com/inward/record.url?scp=0036150473&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0036150473&partnerID=8YFLogxK

U2 - 10.1097/00005344-200202000-00016

DO - 10.1097/00005344-200202000-00016

M3 - Article

C2 - 11791015

AN - SCOPUS:0036150473

VL - 39

SP - 287

EP - 297

JO - Journal of Cardiovascular Pharmacology

JF - Journal of Cardiovascular Pharmacology

SN - 0160-2446

IS - 2

ER -