Prevention of clofilium-induced torsade de pointes by prostaglandin E2 does not involve ATP-dependent K+ channels

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, alpha-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 micromol 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)).