Cardiovascular Toxicology, volume 19, issue 6, pages 518-528
The Use of iPSC-Derived Cardiomyocytes and Optical Mapping for Erythromycin Arrhythmogenicity Testing
Podgurskaya A D
1
,
Tsvelaya V A
1
,
Slotvitsky M M
1
,
Dementyeva E V
2, 3, 4
,
Valetdinova K R
2, 3, 4
,
Publication type: Journal Article
Publication date: 2019-06-05
Journal:
Cardiovascular Toxicology
Quartile SCImago
Q2
Quartile WOS
Q2
Impact factor: 3.2
ISSN: 15307905, 15590259
Molecular Biology
Cardiology and Cardiovascular Medicine
Toxicology
Abstract
Erythromycin is an antibiotic that prolongs the QT-interval and causes Torsade de Pointes (TdP) by blocking the rapid delayed rectifying potassium current (IKr) without affecting either the slow delayed rectifying potassium current (IKs) or inward rectifying potassium current (IK1). Erythromycin exerts this effect in the range of 1.5–100 μM. However, the mechanism of action underlying its cardiotoxic effect and its role in the induction of arrhythmias, especially in multicellular cardiac experimental models, remain unclear. In this study, the re-entry formation, conduction velocity, and maximum capture rate were investigated in a monolayer of human-induced pluripotent stem cell (iPSC)-derived cardiomyocytes from a healthy donor and in a neonatal rat ventricular myocyte (NRVM) monolayer using the optical mapping method under erythromycin concentrations of 15, 30, and 45 μM. In the monolayer of human iPSC-derived cardiomyocytes, the conduction velocity (CV) varied up to 12 ± 9% at concentrations of 15–45 μM as compared with that of the control, whereas the maximum capture rate (MCR) declined substantially up to 28 ± 12% (p < 0.01). In contrast, the tests on the NRVM monolayer showed no significant effect on the MCR. The results of the arrhythmogenicity test provided evidence for a “window” of concentrations of the drug (15–30 μM) at which the probability of re-entry increased.
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- We do not take into account publications that without a DOI.
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Podgurskaya A. D. et al. The Use of iPSC-Derived Cardiomyocytes and Optical Mapping for Erythromycin Arrhythmogenicity Testing // Cardiovascular Toxicology. 2019. Vol. 19. No. 6. pp. 518-528.
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Podgurskaya A. D., Tsvelaya V. A., Slotvitsky M. M., Dementyeva E. V., Valetdinova K. R., Agladze K. I. The Use of iPSC-Derived Cardiomyocytes and Optical Mapping for Erythromycin Arrhythmogenicity Testing // Cardiovascular Toxicology. 2019. Vol. 19. No. 6. pp. 518-528.
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TY - JOUR
DO - 10.1007/s12012-019-09532-x
UR - https://doi.org/10.1007%2Fs12012-019-09532-x
TI - The Use of iPSC-Derived Cardiomyocytes and Optical Mapping for Erythromycin Arrhythmogenicity Testing
T2 - Cardiovascular Toxicology
AU - Podgurskaya, A D
AU - Dementyeva, E V
AU - Valetdinova, K R
AU - Agladze, K. I.
AU - Tsvelaya, V A
AU - Slotvitsky, M M
PY - 2019
DA - 2019/06/05 00:00:00
PB - Springer Nature
SP - 518-528
IS - 6
VL - 19
SN - 1530-7905
SN - 1559-0259
ER -
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@article{2019_Podgurskaya,
author = {A D Podgurskaya and E V Dementyeva and K R Valetdinova and K. I. Agladze and V A Tsvelaya and M M Slotvitsky},
title = {The Use of iPSC-Derived Cardiomyocytes and Optical Mapping for Erythromycin Arrhythmogenicity Testing},
journal = {Cardiovascular Toxicology},
year = {2019},
volume = {19},
publisher = {Springer Nature},
month = {jun},
url = {https://doi.org/10.1007%2Fs12012-019-09532-x},
number = {6},
pages = {518--528},
doi = {10.1007/s12012-019-09532-x}
}
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Podgurskaya, A. D., et al. “The Use of iPSC-Derived Cardiomyocytes and Optical Mapping for Erythromycin Arrhythmogenicity Testing.” Cardiovascular Toxicology, vol. 19, no. 6, Jun. 2019, pp. 518-528. https://doi.org/10.1007%2Fs12012-019-09532-x.