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 language | English |
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Pages (from-to) | 189-196 |
Number of pages | 8 |
Journal | European Journal of Pharmacology |
Volume | 472 |
Issue number | 3 |
DOIs | |
Publication status | Published - 2003 |
Keywords
- torsade de pointes
- proarrhythmia
- QT prolongation
- prostaglandin E2
- K+ channel
- ATP-dependent