On-chip constructive cell-network study (II): On-chip quasi-in vivo cardiac toxicity assay for ventricular tachycardia/fibrillation measurement using ring-shaped closed circuit microelectrode with lined-up cardiomyocyte cell network

Fumimasa Nomura, Tomoyuki Kaneko, Akihiro Hattori, Kenji Yasuda*

*この研究の対応する著者

研究成果: Article査読

16 被引用数 (Scopus)

抄録

Backgrounds: Conventional in vitro approach using human ether-a-go-go related gene (hERG) assay has been considered worldwide as the first screening assay for cardiac repolarization safety. However, it does not always oredict the potential QT prolongation risk or pro-arrhythmic risk correctly. For adaptable preclinical strategiesto evaluate global cardiac safety, an on-chip quasi-in vivo cardiac toxicity assay for lethal arrhythmia (ventricular tachyarrhythmia) measurement using ring-shaped closed circuit microelectrode chip has been developed.Results: The ventricular electrocardiogram (ECG)-like field potential data, which includes both the repolarization and the conductance abnormality, was acquired from the self-convolutied extracellular field potentials (FPs) of a lined-up cardiomyocyte network on a circle-shaped microelectrode in an agarose microchamber. When Astemisol applied to the closed-loop cardiomyocyte network, self-convoluted FP profile of normal beating changed into an early afterdepolarization (EAD) like waveform, and then showed ventricular tachyarrhythmias and ventricular fibrilations (VT/Vf). QT-prolongation-like self-convoluted FP duration prolongation and its fluctuation increase was also observed according to the increase of Astemizole concentration.Conclusions: The results indicate that the convoluted FPs of the quasi-in vivo cell network assay includes both of the repolarization data and the conductance abnormality of cardiomyocyte networks has the strong potential to prediction lethal arrhythmia.

本文言語English
論文番号39
ジャーナルJournal of Nanobiotechnology
9
DOI
出版ステータスPublished - 2011 9月 19
外部発表はい

ASJC Scopus subject areas

  • バイオエンジニアリング
  • 医学(その他)
  • 分子医療
  • 生体医工学
  • 応用微生物学とバイオテクノロジー
  • 薬科学

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