Optimisation of embryonic and larval ECG measurement in zebrafish for quantifying the effect of QT prolonging drugs.

Effective chemical compound toxicity screening is of paramount importance for safe cardiac drug development. Using mammals in preliminary screening for detection of cardiac dysfunction by electrocardiography (ECG) is costly and requires a large number of animals. Alternatively, zebrafish embryos can...

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Autores principales:	Sundeep Singh Dhillon, Eva Dóró, István Magyary, Stuart Egginton, Attila Sík, Ferenc Müller
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/45d5c1deb1fc497ab75c5805542b1a35
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spelling	oai:doaj.org-article:45d5c1deb1fc497ab75c5805542b1a352021-11-18T07:50:17ZOptimisation of embryonic and larval ECG measurement in zebrafish for quantifying the effect of QT prolonging drugs.1932-620310.1371/journal.pone.0060552https://doaj.org/article/45d5c1deb1fc497ab75c5805542b1a352013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23579446/?tool=EBIhttps://doaj.org/toc/1932-6203Effective chemical compound toxicity screening is of paramount importance for safe cardiac drug development. Using mammals in preliminary screening for detection of cardiac dysfunction by electrocardiography (ECG) is costly and requires a large number of animals. Alternatively, zebrafish embryos can be used as the ECG waveform is similar to mammals, a minimal amount of chemical is necessary for drug testing, while embryos are abundant, inexpensive and represent replacement in animal research with reduced bioethical concerns. We demonstrate here the utility of pre-feeding stage zebrafish larvae in detection of cardiac dysfunction by electrocardiography. We have optimised an ECG recording system by addressing key parameters such as the form of immobilization, recording temperature, electrode positioning and developmental age. Furthermore, analysis of 3 days post fertilization (dpf) zebrafish embryos treated with known QT prolonging drugs such as terfenadine, verapamil and haloperidol led to reproducible detection of QT prolongation as previously shown for adult zebrafish. In addition, calculation of Z-factor scores revealed that the assay was sensitive and specific enough to detect large drug-induced changes in QTc intervals. Thus, the ECG recording system is a useful drug-screening tool to detect alteration to cardiac cycle components and secondary effects such as heart block and arrhythmias in zebrafish larvae before free feeding stage, and thus provides a suitable replacement for mammalian experimentation.Sundeep Singh DhillonEva DóróIstván MagyaryStuart EggintonAttila SíkFerenc MüllerPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 4, p e60552 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Sundeep Singh Dhillon Eva Dóró István Magyary Stuart Egginton Attila Sík Ferenc Müller Optimisation of embryonic and larval ECG measurement in zebrafish for quantifying the effect of QT prolonging drugs.
description	Effective chemical compound toxicity screening is of paramount importance for safe cardiac drug development. Using mammals in preliminary screening for detection of cardiac dysfunction by electrocardiography (ECG) is costly and requires a large number of animals. Alternatively, zebrafish embryos can be used as the ECG waveform is similar to mammals, a minimal amount of chemical is necessary for drug testing, while embryos are abundant, inexpensive and represent replacement in animal research with reduced bioethical concerns. We demonstrate here the utility of pre-feeding stage zebrafish larvae in detection of cardiac dysfunction by electrocardiography. We have optimised an ECG recording system by addressing key parameters such as the form of immobilization, recording temperature, electrode positioning and developmental age. Furthermore, analysis of 3 days post fertilization (dpf) zebrafish embryos treated with known QT prolonging drugs such as terfenadine, verapamil and haloperidol led to reproducible detection of QT prolongation as previously shown for adult zebrafish. In addition, calculation of Z-factor scores revealed that the assay was sensitive and specific enough to detect large drug-induced changes in QTc intervals. Thus, the ECG recording system is a useful drug-screening tool to detect alteration to cardiac cycle components and secondary effects such as heart block and arrhythmias in zebrafish larvae before free feeding stage, and thus provides a suitable replacement for mammalian experimentation.
format	article
author	Sundeep Singh Dhillon Eva Dóró István Magyary Stuart Egginton Attila Sík Ferenc Müller
author_facet	Sundeep Singh Dhillon Eva Dóró István Magyary Stuart Egginton Attila Sík Ferenc Müller
author_sort	Sundeep Singh Dhillon
title	Optimisation of embryonic and larval ECG measurement in zebrafish for quantifying the effect of QT prolonging drugs.
title_short	Optimisation of embryonic and larval ECG measurement in zebrafish for quantifying the effect of QT prolonging drugs.
title_full	Optimisation of embryonic and larval ECG measurement in zebrafish for quantifying the effect of QT prolonging drugs.
title_fullStr	Optimisation of embryonic and larval ECG measurement in zebrafish for quantifying the effect of QT prolonging drugs.
title_full_unstemmed	Optimisation of embryonic and larval ECG measurement in zebrafish for quantifying the effect of QT prolonging drugs.
title_sort	optimisation of embryonic and larval ecg measurement in zebrafish for quantifying the effect of qt prolonging drugs.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/45d5c1deb1fc497ab75c5805542b1a35
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Optimisation of embryonic and larval ECG measurement in zebrafish for quantifying the effect of QT prolonging drugs.

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