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- W2892769345 abstract "We examined a simultaneous combined spatiotemporal field potential duration (FPD) and cell-to-cell conduction time (CT) in lined-up shaped human embryonic stem cell-derived cardiomyocytes (hESC-CMs) using an on-chip multielectrode array (MEA) system to evaluate two origins of lethal arrhythmia, repolarization and depolarization. The repolarization index, FPD, was prolonged by E-4031 and astemizole, and shortened by verapamil, flecainide and terfenadine at 10 times higher than therapeutic plasma concentrations of each drug, but it did not change after lidocaine treatment up to 100 μM. CT was increased by astemizol, flecainide, terfenadine, and lidocaine at equivalent concentrations of Nav1.5 IC50, suggesting that CT may be an index of cardiac depolarization because the increase in CT (i.e., decrease in cell-to-cell conduction speed) was relevant to Nav1.5 inhibition. Fluctuations (short-term variability; STV) of FPD and CT, STVFPD and STVCT also discriminated between torsadogenic and non-torsadogenic compounds with significant increases in their fluctuation values, enabling precise prediction of arrhythmogenic risk as potential new indices." @default.
- W2892769345 created "2018-10-05" @default.
- W2892769345 creator A5001341515 @default.
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- W2892769345 date "2018-09-28" @default.
- W2892769345 modified "2023-10-12" @default.
- W2892769345 title "On-chip spatiotemporal electrophysiological analysis of human stem cell derived cardiomyocytes enables quantitative assessment of proarrhythmia in drug development" @default.
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- W2892769345 doi "https://doi.org/10.1038/s41598-018-32921-1" @default.
- W2892769345 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6162288" @default.
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- W2892769345 hasPublicationYear "2018" @default.
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