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)).
Farkas
András
A
Department of Pharmacology and Therapeutics, The University of Liverpool, Ashton Street, Liverpool, L69 3GE, UK.
Coker
Susan J
SJ
D000255:Adenosine Triphosphate / Q000502:physiology*; D000818:Animals; D015232:Dinoprostone / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D015221:Potassium Channels / Q000502:physiology*; D000644:Quaternary Ammonium Compounds / Q000633:toxicity*; D011817:Rabbits; D016171:Torsades de Pointes / Q000139:chemically induced* / Q000188:drug therapy / Q000517:prevention & control*
D015221:Potassium Channels; D000644:Quaternary Ammonium Compounds; C022799:clofilium; D000255:Adenosine Triphosphate; D015232:Dinoprostone