title: Patterned cardiomyocytes on microelectrode arrays as a functional, high information content drug screening platform.
abstract: Cardiac side effects are one of the major causes of drug candidate failures in preclinical drug development or in clinical trials and are responsible for the retraction of several already marketed therapeutics. Thus, the development of a relatively high-throughput, high information content tool to screen drugs and toxins would be important in the field of cardiac research and drug development. In this study, recordings from commercial multielectrode arrays were combined with surface patterning of cardiac myocyte monolayers to enhance the information content of the method; specifically, to enable the measurement of conduction velocity, refractory period after action potentials and to create a functional re-entry model. Two drugs, 1-Heptanol, a gap junction blocker, and Sparfloxacin, a fluoroquinone antibiotic, were tested in this system. 1-Heptanol administration resulted in a marked reduction in conduction velocity, whereas Sparfloxacin caused rapid, irregular and unsynchronized activity, indicating fibrillation. As shown in these experiments, patterning of cardiac myocyte monolayers solved several inherent problems of multielectrode recordings, increased the temporal resolution of conduction velocity measurements, and made the synchronization of external stimulation with action potential propagation possible for refractory period measurements. This method could be further developed as a cardiac side effect screening platform after combination with human cardiomyocytes.
authors: University of Central Florida, NanoScience Technology Center, Orlando, FL 32826, USA.
authors: Anupama
authors: A
authors: Natarajan
authors: Maria
authors: M
authors: Stancescu
authors: Vipra
authors: V
authors: Dhir
authors: Christopher
authors: C
authors: Armstrong
authors: Frank
authors: F
authors: Sommerhage
authors: James J
authors: JJ
authors: Hickman
authors: Peter
authors: P
authors: Molnar
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000995:Antitubercular Agents / Q000494:pharmacology; D002478:Cells, Cultured; D002986:Clinical Trials as Topic; D016895:Culture Media, Serum-Free; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D024841:Fluoroquinolones / Q000494:pharmacology; D019850:Heptanol / Q000494:pharmacology; D006801:Humans; D008839:Microelectrodes; D032383:Myocytes, Cardiac / Q000166:cytology*
chemical_list: D000995:Antitubercular Agents; D016895:Culture Media, Serum-Free; D024841:Fluoroquinolones; D019850:Heptanol; C061363:sparfloxacin