Effects of cardioactive drugs on human induced pluripotent stem cell derived long QT syndrome cardiomyocytes

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Kuusela , J , Kujala , V J , Kiviaho , A , Ojala , M , Swan , H , Kontula , K & Aalto-Setala , K 2016 , ' Effects of cardioactive drugs on human induced pluripotent stem cell derived long QT syndrome cardiomyocytes ' , SpringerPlus , vol. 5 , 234 . https://doi.org/10.1186/s40064-016-1889-y

Title: Effects of cardioactive drugs on human induced pluripotent stem cell derived long QT syndrome cardiomyocytes
Author: Kuusela, Jukka; Kujala, Ville J.; Kiviaho, Anna; Ojala, Marisa; Swan, Heikki; Kontula, Kimmo; Aalto-Setala, Katriina
Contributor: University of Helsinki, Clinicum
University of Helsinki, Clinicum
Date: 2016-02-29
Language: eng
Number of pages: 13
Belongs to series: SpringerPlus
ISSN: 2193-1801
URI: http://hdl.handle.net/10138/161076
Abstract: Human induced pluripotent stem cells (hiPSC) have enabled a major step forward in pathophysiologic studies of inherited diseases and may also prove to be valuable in in vitro drug testing. Long QT syndrome (LQTS), characterized by prolonged cardiac repolarization and risk of sudden death, may be inherited or result from adverse drug effects. Using a microelectrode array platform, we investigated the effects of six different drugs on the electrophysiological characteristics of human embryonic stem cell-derived cardiomyocytes as well as hiPSC-derived cardiomyocytes from control subjects and from patients with type 1 (LQT1) and type 2 (LQT2) of LQTS. At baseline the repolarization time was significantly longer in LQTS cells compared to controls. Isoprenaline increased the beating rate of all cell lines by 10-73 % but did not show any arrhythmic effects in any cell type. Different QT-interval prolonging drugs caused prolongation of cardiac repolarization by 3-13 % (cisapride), 10-20 % (erythromycin), 8-23 % (sotalol), 16-42 % (quinidine) and 12-27 % (E-4031), but we did not find any systematic differences in sensitivity between the control, LQT1 and LQT2 cell lines. Sotalol, quinidine and E-4031 also caused arrhythmic beats and beating arrests in some cases. In summary, the drug effects on these patient-specific cardiomyocytes appear to recapitulate clinical observations and provide further evidence that these cells can be applied for in vitro drug testing to probe their vulnerability to arrhythmia.
Subject: Induced pluripotent stem cell
Patient-specific
Long QT syndrome
Cardiomyocytes
Multielectrode array
Cardioactive drug
Arrhythmia
TORSADES-DE-POINTES
POTASSIUM CHANNEL
FOUNDER MUTATIONS
HUMAN HEART
KVLQT1
REPOLARIZATION
DIFFERENTIATION
PROLONGATION
ARRHYTHMIAS
PREVALENCE
3121 General medicine, internal medicine and other clinical medicine
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