当前位置： SCI文献检索 > JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY期刊下所有文献 > In vivo effects of mutant HERG K+ channel inhibition by disopyramide in patients with a short QT-1 syndrome: a pilot study.

In vivo effects of mutant HERG K+ channel inhibition by disopyramide in patients with a short QT-1 syndrome: a pilot study.

Abstract：

INTRODUCTION:Quinidine has been evaluated in patients with a short QT-1 syndrome caused by an IKr gain-of-function mutation of HERG. Recently, in vitro data with disopyramide showed an even stronger effect on the N588K mutant current. The aim of the present study was to test the in vivo effects of disopyramide in patients with short QT-1 syndrome caused by a N588K mutation in HERG. METHODS AND RESULTS:Repetitive ECGs were recorded in two female patients with short QT-1 syndrome with a N588K-HERG mutation off drugs, on oral quinidine, and on oral disopyramide. One patient underwent exercise testing on drugs to determine the QT interval to heart rate relation, whereas the QT interval was calculated to the peak of the T wave in lead V3. In the same patient, drug-induced changes in ventricular effective refractory periods were determined by programmed ventricular stimulation via the ICD lead. Disopyramide increased the QT interval from QTc 329 ms/QTc 315 ms, respectively, off drugs to QTc 358 ms/QTc 333 ms in both patients and restored the heart rate dependence of the QT interval toward normal subjects (-0.39 ms/bpm off drugs, -0.58 ms/bpm on disopyramide vs. 1.29 +/- 0.33 ms/bpm in normal subjects). The ventricular effective refractory period increased under disopyramide by 40 ms. CONCLUSION:These preliminary observations suggest that oral disopyramide may be a suitable alternative to quinidine for prolonging the QT interval and ventricular effective refractory periods in patients with short QT-1 syndrome. Further studies of this pharmacologic approach are warranted.

journal_name

J Cardiovasc Electrophysiol

journal_title

Journal of cardiovascular electrophysiology

authors

Schimpf R,Veltmann C,Giustetto C,Gaita F,Borggrefe M,Wolpert C

doi

10.1111/j.1540-8167.2007.00925.x

subject

Has Abstract

pub_date

2007-11-01 00:00:00

pages

1157-60

issue

11

eissn

1045-3873

issn

1540-8167

pii

JCE925

journal_volume

18

pub_type

杂志文章

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