Linked Life Data

16842817

Source:http://linkedlifedata.com/resource/pubmed/id/16842817

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2006-9-15
pubmed:abstractText
The recently identified idiopathic short QT syndrome (SQTS) is associated with an increased risk of arrhythmia and sudden death. The use of implantable cardioverter defibrillators helps to protect SQTS patients from ventricular fibrillation; however, pharmacological treatments to normalise the QT interval are limited: thus far only quinidine has been found to be effective in a subset of patients, with the SQT1 variant. SQT1 is associated with an amino acid substitution (N588K) in the KCNH2-encoded HERG K(+) channel that reduces HERG current (I(HERG)) inactivation and sensitivity to drug block. We demonstrate here that the N588K-HERG mutation only slightly attenuates I(HERG) blockade by the Class Ia antiarrhythmic drug disopyramide (1.5-fold elevation of IC(50)), compared to quinidine (3.5-fold elevation of IC(50)) and the Class III antiarrhythmic drug E-4031 (11.5-fold elevation of IC(50)). Thus, of the drugs studied to date, disopyramide is the one least affected by the SQT1 HERG mutation. Disopyramide is associated with QT prolongation in normal use and our findings provide a rational basis for its evaluation as a treatment for SQT1.
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0022-2828
pubmed:author
pubmed:issnType
Print
pubmed:volume
41
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
563-6
pubmed:dateRevised
2008-10-28
pubmed:meshHeading
pubmed:year
2006
pubmed:articleTitle
Disopyramide is an effective inhibitor of mutant HERG K+ channels involved in variant 1 short QT syndrome.
pubmed:affiliation
Department of Physiology and Cardiovascular Research Laboratories, School of Medical Sciences, University Walk, University of Bristol, BS8 1TD, UK.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't