Abstract 20919: Manipulation-Free Particle Image Velocimetry Method of Screening Drugs Using Human iPSC-Derived Cardiomyocytes
| Autor: | Sheeja Rajasingh, Andras Czirok, Dona G Isai, Saheli Samanta, Zhigang Zhou, Bahar Barani, Nicholas Drosos, Buddhadeb Dawn, Johnson Rajasingh |
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| Rok vydání: | 2017 |
| Předmět: | |
| Zdroj: | Circulation. 136 |
| ISSN: | 1524-4539 0009-7322 |
| Popis: | Introduction: Currently available drug screening models are not efficient in detecting cardiac toxicity. Here we demonstrate the in vitro Particle Image Velocimetry (PIV) assays followed by fourier spectrum and heatmap analyses for measuring the impact of different cardiac drugs on the spontaneous beat frequency (SBF) and spontaneous beat amplitude (SBA) of beating cardiomyocytes (CMCs). Hypothesis: Our PIV method of measuring CMCs contractility could be beneficial for drug testing and preclinical screening to detect cardio-toxicity. Methods and Results: The novelty of our system is that we can record the spatiotemporal maturation of human iPSC-derived CMCs at specific positions. We have evaluated the contractility of CMCs with the response to various chemical compounds such as Verapamil (Ca2+ blocker), Isoproterenol (Ca2+ activator), E-4031 (K+ inhibitor) and NS-1643 (K+ activator). Our optically recorded beat patterns were in good agreement with the calcium-imaging signal ( Fig 1 ). Our data also show that Isoproterenol, the β adrenergic agonist influencing intracellular Ca2+ dynamics, induced a substantial and sustained increase in SBF without triggering arrhythmias (Fig 2A, B) . Fourier analysis clearly indicates a shift in the SBF (Fig. 2C , dotted line). Power spectra of consecutive recordings are shown as heat maps ( Fig. 2D ). The reversibility of the Isoproterenol effect is indicated by the SBF returning to the baseline value after drug removal (Fig 2B, E ). Conclusions: We report for the first time the applications of PIV assays for prospective cardiac drug efficacy screening by measuring the contractility of CMCs from the video image without jeopardizing the biology of cells. |
| Databáze: | OpenAIRE |
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