Abstract
| Language | English |
|---|---|
| Pages | 189-196 |
| Number of pages | 8 |
| Journal | European Journal of Pharmacology |
| Volume | 472 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - 2003 |
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Keywords
- torsade de pointes
- proarrhythmia
- QT prolongation
- prostaglandin E2
- K+ channel
- ATP-dependent
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Prevention of clofilium-induced torsade de pointes by prostaglandin E2 does not involve ATP-dependent k+ channels. / Farkas, A.; Coker, Susan J.
In: European Journal of Pharmacology, Vol. 472, No. 3, 2003, p. 189-196.Research output: Contribution to journal › Article
TY - JOUR
T1 - Prevention of clofilium-induced torsade de pointes by prostaglandin E2 does not involve ATP-dependent k+ channels
AU - Farkas, A.
AU - Coker, Susan J.
PY - 2003
Y1 - 2003
N2 - 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).
AB - 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).
KW - torsade de pointes
KW - proarrhythmia
KW - QT prolongation
KW - prostaglandin E2
KW - K+ channel
KW - ATP-dependent
U2 - 10.1016/S0014-2999(03)01910-1
DO - 10.1016/S0014-2999(03)01910-1
M3 - Article
VL - 472
SP - 189
EP - 196
JO - European Journal of Pharmacology
T2 - European Journal of Pharmacology
JF - European Journal of Pharmacology
SN - 0014-2999
IS - 3
ER -