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Antiarrhythmic effects of vernakalant in human-induced pluripotent stem cell-derived cardiomyocytes from a patient with short QT syndrome type 1

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(1) Background: Short QT syndrome (SQTS) may result in sudden cardiac death. So far, no drugs, except quinidine, have been demonstrated to be effective in some patients with SQTS type 1 (SQTS1). This study was designed to examine the potential effectiveness of vernakalant for treating SQTS1 patients...

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Main Authors: Xu, Qiang (Author) , Huang, Xuemei (Author) , Meng, Zenghui (Author) , Li, Yingrui (Author) , Zhong, Rujia (Author) , Li, Xin (Author) , Cyganek, Lukas (Author) , El-Battrawy, Ibrahim (Author) , Akın, Ibrahim (Author) , Zhou, Xiao-Bo (Author) , Lan, Huan (Author)
Format: Article (Journal)
Language:English
Published: 9 April 2022
In: Journal of cardiovascular development and disease
Year: 2022, Volume: 9, Issue: 4, Pages: 1-14
ISSN:2308-3425
DOI:10.3390/jcdd9040112
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.3390/jcdd9040112
Verlag, kostenfrei, Volltext: https://www.mdpi.com/2308-3425/9/4/112
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Author Notes:Qiang Xu, Xuemei Huang, Zenghui Meng, Yingrui Li, Rujia Zhong, Xin Li, Lukas Cyganek, Ibrahim El-Battrawy, Ibrahim Akin, Xiaobo Zhou and Huan Lan
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Summary:(1) Background: Short QT syndrome (SQTS) may result in sudden cardiac death. So far, no drugs, except quinidine, have been demonstrated to be effective in some patients with SQTS type 1 (SQTS1). This study was designed to examine the potential effectiveness of vernakalant for treating SQTS1 patients, using human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) from a patient with SQTS1. (2) Methods: Patch clamp and calcium imaging techniques were used to examine the drug effects. (3) Results: Vernakalant prolonged the action potential duration (APD) in hiPSC-CMs from a SQTS1-patient (SQTS1-hiPSC-CMs). In spontaneously beating SQTS1-hiPSC-CMs, vernakalant reduced the arrhythmia-like events induced by carbachol plus epinephrine. Vernakalant failed to suppress the hERG channel currents but reduced the outward small-conductance calcium-activated potassium channel current. In addition, it enhanced Na/Ca exchanger currents and late sodium currents, in agreement with its APD-prolonging effect. (4) Conclusions: The results demonstrated that vernakalant can prolong APD and reduce arrhythmia-like events in SQTS1-hiPSC-CMs and may be a candidate drug for treating arrhythmias in SQTS1-patients.
Item Description:Gesehen am 02.04.2024
Physical Description:Online Resource
ISSN:2308-3425
DOI:10.3390/jcdd9040112

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