Universität zu Köln

Niehoff, Julius, Matzkies, Matthias, Nguemo, Filomain, Hescheler, Juergen and Repperl, Michael (2016). Beat Rate Variability in Murine Embryonic Stem Cell-Derived Cardiomyocytes: Effect of Antiarrhythmic Drugs. Cell. Physiol. Biochem., 38 (2). S. 646 - 659. BASEL: KARGER. ISSN 1421-9778

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Abstract

Background/Aims: Heart rate variability (HRV) refers to the fluctuation of the time interval between consecutive heartbeats in humans. It has recently been discovered that cardiomyocytes derived from human embryonic and induced pluripotent stem cells show beat rate variability (BRV) that is similar to the HRV in humans. In the present study, clinical aspects of HRV were transferred to an in vitro model. The aims of the study were to explore the BRV in murine embryonic stem cell (mESC)-derived cardiomyocytes and to demonstrate the influence of antiarrhythmic drugs on BRV as has been shown in clinical trials previously. Methods: The Microelectrode Array (MEA) technique was used to perform short-term recordings of extracellular field potentials (FPs) of spontaneously beating cardiomyocytes derived from mESCs (D3 cell line, alpha Pig-44). Offline analysis was focused on time domain and nonlinear methods. Results: The Poincare-Plot analysis of measurements without pharmacological intervention revealed that three different shapes of scatter plots occurred most frequently. Comparable shapes have been described in clinical studies before. The antiarrhythmic drugs Ivabradine, Verapamil and Sotalol augmented BRV, whereas Flecainide decreased BRV parameters at low concentrations (SDSD 79.0 +/- 8.7% of control at 10(-9) M, p < 0.05) and increased variability measures at higher concentrations (SDNN 258.8 +/- 42.7% of control at 10(-5) M, p < 0.05). Amiodarone and Metoprolol did not alter BRV significantly. Conclusions: Spontaneously beating cardiomyocytes derived from mESCs showed BRV that appears to be similar to the HRV known from humans. Antiarrhythmic drugs affected BRV parameters similar to clinical observations. Therefore, our study demonstrates that this in vitro model can contribute to a better understanding of electrophysiological properties of mESC-derived cardiomyocytes and might serve as a valuable tool for drug safety screening. (C) 2016 The Author(s) Published by S. Karger AG, Basel

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Niehoff, Julius UNSPECIFIED UNSPECIFIED UNSPECIFIED Matzkies, Matthias UNSPECIFIED UNSPECIFIED UNSPECIFIED Nguemo, Filomain UNSPECIFIED UNSPECIFIED UNSPECIFIED Hescheler, Juergen UNSPECIFIED UNSPECIFIED UNSPECIFIED Repperl, Michael UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-291071
DOI:	10.1159/000438657
Journal or Publication Title:	Cell. Physiol. Biochem.
Volume:	38
Number:	2
Page Range:	S. 646 - 659
Date:	2016
Publisher:	KARGER
Place of Publication:	BASEL
ISSN:	1421-9778
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language HEART-RATE-VARIABILITY; ACUTE MYOCARDIAL-INFARCTION; VENTRICULAR-ARRHYTHMIAS; CARDIOACTIVE DRUGS; FAILURE; FLECAINIDE; METOPROLOL; MORTALITY; PACEMAKER; VERAPAMIL Multiple languages Cell Biology; Physiology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/29107