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CARDIOTOXICITY

Z-Tag Fluorescent Heart embryos facilitate automated analysis of heart rate and rhythmicity. Heart rate measurements can be used to identify compounds that cause bradycardia or tachycardia and heart beat patterns can be used to predict compounds which affect rhythmicity in humans. In one application, compounds linked to QT prolongation in humans (such as terfenadine and  astemizole) have been shown to induce bradycardia in zebrafish embryos. In addition, drug-drug interactions can be assessed in zebrafish embryos.  For example, cisapride-erythromycin and terfenadine-cimetidine combinations reduced the heart rate of treated embryos in an additive manner.



Heart rate of untreated zebrafish embryo (acquired at 10X magnification)
(.8 MB movie)


Heart rate of zebrafish embryo treated with amiodarone exhibits bradycardia and A-V nodal block.
(1.5 MB movie)
 
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