%0 Journal Article
%T Beat-to-Beat Variability in Field Potential Duration in Human Embryonic Stem Cell-Derived Cardiomyocyte Clusters for Assessment of Arrhythmogenic Risk, and a Case Study of Its Application
%A Kazuto Yamazaki
%A Taro Hihara
%A Hiroshi Kato
%A Tatsuto Fukushima
%A Kazuyuki Fukushima
%A Tomohiko Taniguchi
%A Takashi Yoshinaga
%A Norimasa Miyamoto
%A Masashi Ito
%A Kohei Sawada
%J Pharmacology & Pharmacy
%P 117-128
%@ 2157-9431
%D 2014
%I Scientific Research Publishing
%R 10.4236/pp.2014.51017
%X <p>
	<span style=\"font-family:Verdana;\">We established a QT</span><span> </span><span style=\"font-family:Verdana;\">interval assessment system that uses
human embryonic</span><span> </span><span style=\"font-family:Verdana;\">stem</span><span> </span><span style=\"font-family:Verdana;\">cell</span><span style=\"font-family:Verdana;\">-</span><span style=\"font-family:Verdana;\">derived cardiomyocyte clusters (hES-CMCs) in which the field potential
duration (FPD) or corrected FPD (FPDc) was measured as an indicator of
drug-induced QT interval prolongation. To investigate the applicability of the
hES-CMC system to drug safety assessment, we investigated</span><span> </span><span><span style=\"font-family:Verdana;\">short-term variability in FPDc (STV</span><sub><span style=\"font-family:Verdana;\">FPDc</span></sub><span style=\"font-family:Verdana;\">) (beat rate
rhythmicity) as a marker of torsadogenic risk.</span></span><span> </span><span><span style=\"font-family:Verdana;\">We investigated
the FPDc and STV</span><sub><span style=\"font-family:Verdana;\">FPDc</span></sub><span style=\"font-family:Verdana;\"> of hES-CMCs treated with</span></span><span> </span><span><span style=\"font-family:Verdana;\">hERG channel </span><span style=\"font-family:Verdana;\">blockers (E-4031 or</span></span><span> </span><span style=\"font-family:Verdana;\">cisapride) or
with our proprietary</span><span> </span><span style=\"font-family:Verdana;\">compounds X, Y, and Z. We</span><span> </span><span style=\"font-family:Verdana;\">also evaluated the electrocardiograms and hemodynamics of</span><span> </span><span style=\"font-family:Verdana;\">dogs treated with
compound X, Y,</span><span> </span><span style=\"font-family:Verdana;\">or Z.</span><span> </span><span style=\"font-family:Verdana;\">The</span><span> </span><span style=\"font-family:Verdana;\">torsadogenic</span><span> </span><span><span style=\"font-family:Verdana;\">hERG channel
blockers increased STV</span><sub><span style=\"font-family:Verdana;\">FPDc</span></sub></span><span> </span><span style=\"font-family:Verdana;\">and prolonged FPDc.</span><span> </span><span style=\"font-family:Verdana;\">Compounds X, Y, and Z had hERG inhibitory activity.
Compound </span><span><span style=\"font-family:Verdana;\">X prolonged FPDc
with increased STV</span><sub><span style=\"font-family:Verdana;\">FPDc</span></sub><span style=\"font-family:Verdana;\">, whereas compounds Y and Z tended to shorten</span></span><span> </span><span style=\"font-family:Verdana;\">FPDc in the hES-CMC system.</span><span>
%K Human Embryonic Stem Cell-Derived Cardiomyocytes
%K Field Potential Duration
%K Short-Term Variability
%K QT Interval
%K Torsades de Pointes
%K Risk Assessment
%U http://www.scirp.org/journal/PaperInformation.aspx?PaperID=42388