Enhancement of delayed afterdepolarizations and triggered activity by class III antiarrhythmic drugs: Multiple effects of E-4031 and dofetilide

J. T. Xie, Chun Su Yuan, Zhengfeng Zhou, C. T. January

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

The effects of class III antiarrhythmic agents E.4031 and dofetilide were studied on action potentials and subthreshold delayed afterdepolarizations (DADs) induced by the cardiac glycoside acetylstrophanthidin (AS) in isolated cardiac Purkinje fibers. Action potentials were recorded from cardiac Purkinje fibers using microelectrode techniques. E-4031 and dofetilide consistently increased DAD amplitude, occasionally, caused triggered action potentials and shortened action potential duration. The application of E-4031 without prior AS exposure, resulted in the typical class III antiarrhythmic effects of action potential lengthening and the induction of early afterdepolarizations. These findings suggest that tinder our conditions of AS-induced cell Ca2+ overload, the effects of the 'pure' class III antiarrhythmic drugs, E-4031 and dofetilide, are markedly different from those found in non-Ca2+ loaded cells. This may represent an additional electrophysiological mechanism for class III antiarrhythmic drug toxicity. (C) 2000 Prous Science.

Original languageEnglish (US)
Pages (from-to)67-76
Number of pages10
JournalMethods and Findings in Experimental and Clinical Pharmacology
Volume22
Issue number2
StatePublished - 2000
Externally publishedYes

Fingerprint

Anti-Arrhythmia Agents
Action Potentials
Purkinje Fibers
Cardiac Glycosides
Microelectrodes
Drug-Related Side Effects and Adverse Reactions
dofetilide
E 4031
acetylstrophanthidin

Keywords

  • Cardiac glycoside
  • Delayed afterdepolarization
  • Dofetilide
  • E-4031
  • Early afterdepolarization
  • Triggered arrhythmias

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

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abstract = "The effects of class III antiarrhythmic agents E.4031 and dofetilide were studied on action potentials and subthreshold delayed afterdepolarizations (DADs) induced by the cardiac glycoside acetylstrophanthidin (AS) in isolated cardiac Purkinje fibers. Action potentials were recorded from cardiac Purkinje fibers using microelectrode techniques. E-4031 and dofetilide consistently increased DAD amplitude, occasionally, caused triggered action potentials and shortened action potential duration. The application of E-4031 without prior AS exposure, resulted in the typical class III antiarrhythmic effects of action potential lengthening and the induction of early afterdepolarizations. These findings suggest that tinder our conditions of AS-induced cell Ca2+ overload, the effects of the 'pure' class III antiarrhythmic drugs, E-4031 and dofetilide, are markedly different from those found in non-Ca2+ loaded cells. This may represent an additional electrophysiological mechanism for class III antiarrhythmic drug toxicity. (C) 2000 Prous Science.",
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T2 - Multiple effects of E-4031 and dofetilide

AU - Xie, J. T.

AU - Yuan, Chun Su

AU - Zhou, Zhengfeng

AU - January, C. T.

PY - 2000

Y1 - 2000

N2 - The effects of class III antiarrhythmic agents E.4031 and dofetilide were studied on action potentials and subthreshold delayed afterdepolarizations (DADs) induced by the cardiac glycoside acetylstrophanthidin (AS) in isolated cardiac Purkinje fibers. Action potentials were recorded from cardiac Purkinje fibers using microelectrode techniques. E-4031 and dofetilide consistently increased DAD amplitude, occasionally, caused triggered action potentials and shortened action potential duration. The application of E-4031 without prior AS exposure, resulted in the typical class III antiarrhythmic effects of action potential lengthening and the induction of early afterdepolarizations. These findings suggest that tinder our conditions of AS-induced cell Ca2+ overload, the effects of the 'pure' class III antiarrhythmic drugs, E-4031 and dofetilide, are markedly different from those found in non-Ca2+ loaded cells. This may represent an additional electrophysiological mechanism for class III antiarrhythmic drug toxicity. (C) 2000 Prous Science.

AB - The effects of class III antiarrhythmic agents E.4031 and dofetilide were studied on action potentials and subthreshold delayed afterdepolarizations (DADs) induced by the cardiac glycoside acetylstrophanthidin (AS) in isolated cardiac Purkinje fibers. Action potentials were recorded from cardiac Purkinje fibers using microelectrode techniques. E-4031 and dofetilide consistently increased DAD amplitude, occasionally, caused triggered action potentials and shortened action potential duration. The application of E-4031 without prior AS exposure, resulted in the typical class III antiarrhythmic effects of action potential lengthening and the induction of early afterdepolarizations. These findings suggest that tinder our conditions of AS-induced cell Ca2+ overload, the effects of the 'pure' class III antiarrhythmic drugs, E-4031 and dofetilide, are markedly different from those found in non-Ca2+ loaded cells. This may represent an additional electrophysiological mechanism for class III antiarrhythmic drug toxicity. (C) 2000 Prous Science.

KW - Cardiac glycoside

KW - Delayed afterdepolarization

KW - Dofetilide

KW - E-4031

KW - Early afterdepolarization

KW - Triggered arrhythmias

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