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

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 E 2, alters the proarrhythmic effects of clofilium. In pentobarbitone-anaesthetized, open-chest, α-adrenoceptor-stimulated rabbits, prostaglandin E 2 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 E 2 (2.80 nmol kg −1 min −1). These results indicate that prostaglandin E 2 prevents drug-induced torsade de pointes and that this action of prostaglandin E 2 is not mediated via opening of ATP-dependent K + channels (K ATP).