In:
Clinical Pharmacology & Therapeutics, Wiley, Vol. 106, No. 3 ( 2019-09), p. 642-651
Abstract:
Short QT syndrome ( SQTS ) predisposes afflicted patients to sudden cardiac death. Until now, only one drug—quinidine—has been shown to be effective in patients with SQTS type 1( SQTS 1). The objective of this study was to use human‐induced pluripotent stem cell–derived cardiomyocytes (hi PSC ‐ CM s) from a patient with SQTS 1 to search for potentially effective drugs for the treatment of SQTS 1 patients. Patch clamp and single‐cell contraction measurements were employed to assess drug effects. Ivabradine, mexiletine, and ajmaline but not flecainide, ranolazine, or amiodarone prolonged the action potential duration ( APD ) in hi PSC ‐ CM s from an SQTS 1 patient. Ivabradine, ajmaline, and mexiletine inhibited KCNH 2 channel currents significantly, which may underlie their APD ‐prolonging effects. Under proarrhythmic epinephrine stimulation in spontaneously beating SQTS 1 hi PSC ‐ CM s, ivabradine, mexiletine, and ajmaline but not flecainide reduced the epinephrine‐induced arrhythmic events. The results demonstrate that ivabradine, ajmaline, and mexiletine may be candidate drugs for preventing tachyarrhythmias in SQTS 1 patients.
Type of Medium:
Online Resource
ISSN:
0009-9236
,
1532-6535
Language:
English
Publisher:
Wiley
Publication Date:
2019
detail.hit.zdb_id:
2040184-X
SSG:
15,3
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