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Drug Testing in Human‐Induced Pluripotent Stem Cell–Derived Cardiomyocytes From a Patient With Short QT Syndrome Type 1
Author(s) -
Zhao Zhihan,
Li Xin,
ElBattrawy Ibrahim,
Lan Huan,
Zhong Rujia,
Xu Qiang,
Huang Mengying,
Liao Zhenxing,
Lang Siegfried,
Zimmermann WolframHubertus,
Cyganek Lukas,
Wieland Thomas,
Akin Ibrahim,
Zhou XiaoBo,
Borggrefe Martin
Publication year - 2019
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1002/cpt.1449
Subject(s) - mexiletine , flecainide , short qt syndrome , medicine , ajmaline , ivabradine , cardiology , amiodarone , pharmacology , anesthesia , qt interval , long qt syndrome , heart rate , atrial fibrillation , blood pressure
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.