Optimisation of embryonic and larval ECG measurement in zebrafish for quantifying the effect of QT prolonging drugs
| Autor: | Ferenc Müller, Éva Dóró, Attila Sik, Stuart Egginton, István Magyary, Sundeep Singh Dhillon |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Embryology
Anatomy and Physiology Drug Evaluation Preclinical Pharmacology Toxicology Bioinformatics Cardiovascular System Ion Channels Electrocardiography Drug Discovery Morphogenesis Medicine Zebrafish Multidisciplinary medicine.diagnostic_test Cardiac cycle biology Heart Animal Models Drug development Toxicity Artifacts Research Article medicine.drug Drugs and Devices Drug Research and Development animal structures Science Predictive Toxicology Celbiologie en Immunologie QT interval Model Organisms Animals Life Science ECG Measurement Biology business.industry fungi Reproducibility of Results biology.organism_classification Cell Biology and Immunology Cardiovascular Anatomy Verapamil business Developmental Biology |
| Zdroj: | PLoS ONE, Vol 8, Iss 4, p e60552 (2013) PLoS ONE, 8(4) PLoS ONE 8 (2013) 4 PLoS ONE |
| ISSN: | 1932-6203 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|