Linked Life Data

11752098

Source:http://linkedlifedata.com/resource/pubmed/id/11752098

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2001-12-25
pubmed:abstractText
There is growing concern that antipsychotic drugs that prolong the QT interval almost always increase the risk for patients to develop life-threatening ventricular tachyarrhythmias (VTs) of the torsade de pointes type. We therefore sought to compare the electrophysiologic effects of the psychotropic agent sertindole, which prolongs cardiac repolarization by inhibiting the rapid component of the delayed rectifier potassium current (I(Kr)) but has a low torsadogenic potential to the antiarrhythmic agent dl-sotalol. In 18 Langendorff-perfused rabbit hearts, sotalol (10 microM, n = 8) and sertindole (0.5, 1.0, and 1.5 microM; n = 10) led to significant and comparable QT prolongation. In the presence of sotalol, torsade de pointes reproducibly occurred in atrioventricular node-blocked hearts after lowering the potassium concentration to 1.5 mM. High doses of sertindole (1.5 microM) only caused monomorphic VT (n = 4) and nonsustained polymorphic VT (n = 2) in the presence of QRS prolongation. Multiple simultaneous epi- and endocardial monophasic action potentials and a volume-conducted ECG demonstrated widening of the T/U wave, early afterdepolarizations, and increased dispersion of repolarization in the presence of dl-sotalol. In contrast to sotalol, QT and monophasic action potential prolongation were cycle length-independent in the presence of sertindole. Sertindole had no significant effect on transmural or interventricular dispersion of repolarization. Early afterdepolarizations did not occur. Despite comparable QT prolongation, sertindole did not display the proarrhythmic profile typical of other blockers of I(Kr) such as dl-sotalol. It is likely that a different mode of interaction between sertindole and the channel and/or additional pharmacological effects of sertindole, e.g., its ability to inhibit I(Na) and/or its ability to block alpha(1)-receptors, play a role.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0022-3565
pubmed:author
pubmed:issnType
Print
pubmed:volume
300
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
64-71
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed:year
2002
pubmed:articleTitle
Electrophysiologic characterization of the antipsychotic drug sertindole in a rabbit heart model of torsade de pointes: low torsadogenic potential despite QT prolongation.
pubmed:affiliation
Hospital of the Westfälische Wilhelms-University, Department of Cardiology and Angiology and Institute for Arteriosclerosis Research, Münster, Germany. l.eckhardt@uni-muenster.de
pubmed:publicationType
Journal Article, In Vitro