title: 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.
abstract: BACKGROUND
  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.
authors.affiliation: Department of Biomedical Information, Division of Biosystems, Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, 2-3-10 Kanda-Surugadai, Chiyoda, Tokyo 101-0062, Japan.
authors.forename: Fumimasa
authors.initials: F
authors.lastname: Nomura
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Kaneko
authors.forename: Akihiro
authors.initials: A
authors.lastname: Hattori
authors.forename: Kenji
authors.initials: K
authors.lastname: Yasuda
mesh_terms: D000818:Animals; D016589:Astemizole / Q000009:adverse effects* / Q000494:pharmacology; D002450:Cell Communication / Q000187:drug effects* / Q000502:physiology; D018929:Cell Culture Techniques; D039563:Histamine H1 Antagonists, Non-Sedating / Q000009:adverse effects* / Q000494:pharmacology; D051379:Mice; D008839:Microelectrodes; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000502:physiology; D017180:Tachycardia, Ventricular / Q000139:chemically induced* / Q000503:physiopathology; D014693:Ventricular Fibrillation / Q000139:chemically induced* / Q000503:physiopathology
chemical_list: D039563:Histamine H1 Antagonists, Non-Sedating; D016589:Astemizole