Prevention of clofilium-induced torsade de pointes by prostaglandin E 2 does not involve ATP-dependent K+ channels

A. Farkas, Susan J. Coker

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Drugs that prolong the QT interval can trigger the life-threatening arrhythmia, torsade de pointes, but there is a poor correlation between the extent of QT prolongation and the occurrence of torsade de pointes. The clinical status of a patient may modify the arrhythmogenicity of drugs; thus, we have investigated whether a mediator of fever and inflammation, prostaglandin E2, alters the proarrhythmic effects of clofilium. In pentobarbitone-anaesthetized, open-chest, α-adrenoceptor-stimulated rabbits, prostaglandin E2 0.28, 0.84 and 2.80 nmol kg-1 min-1, infused into the left ventricle, reduced the incidence of torsade de pointes from 50% in controls to 20%, 20% and 0%, respectively (n=10 per group). Pretreatment with glibenclamide (10 μmol kg-1) did not alter the antiarrhythmic effect of prostaglandin E2 (2.80 nmol kg-1 min-1). These results indicate that prostaglandin E2 prevents drug-induced torsade de pointes and that this action of prostaglandin E2 is not mediated via opening of ATP-dependent K + channels (KATP).

Original languageEnglish
Pages (from-to)189-196
Number of pages8
JournalEuropean Journal of Pharmacology
Volume472
Issue number3
DOIs
Publication statusPublished - Jul 11 2003

Fingerprint

Torsades de Pointes
Prostaglandins E
Dinoprostone
Adenosine Triphosphate
Pharmaceutical Preparations
Inflammation Mediators
KATP Channels
Glyburide
Pentobarbital
Adrenergic Receptors
Heart Ventricles
Cardiac Arrhythmias
Fever
Thorax
clofilium
Rabbits
Incidence

Keywords

  • ATP-dependent K channel
  • K channel
  • Proarrhythmia
  • Prostaglandin E
  • QT prolongation
  • Torsade de pointes

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Pharmacology

Cite this

Prevention of clofilium-induced torsade de pointes by prostaglandin E 2 does not involve ATP-dependent K+ channels. / Farkas, A.; Coker, Susan J.

In: European Journal of Pharmacology, Vol. 472, No. 3, 11.07.2003, p. 189-196.

Research output: Contribution to journalArticle

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