Development of tools for embryonic ECG for heart dysfunction in zebrafish

Hurst, Rhiannon Mary (2018). Development of tools for embryonic ECG for heart dysfunction in zebrafish. University of Birmingham. Ph.D.

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In the past decade, the zebrafish, Danio rerio, has risen to much greater prominence as a vertebrate model system for drug discovery and toxicity testing. Zebrafish larvae represent an in vivo vertebrate model, with high throughput potential and proven efficacy as a model of human disease and drug responses. Specifically, zebrafish have been used for cardiotoxicity studies and cardiac arrhythmia modelling.

This project aims to develop and optimise tools for electrocardiographic recording in zebrafish larvae for use in cardiotoxicity screening and human arrhythmia modelling. Steps were taken towards a high throughput ECG system for zebrafish larvae through establishing viability of non-contact capillary electrode recording and development of microfabricated electrode arrays capable of replacing glass capillary electrodes. In depth analysis of atrium and ventricle signals using wavelet analysis was performed and the frequency profiles for these chambers examined. The utility of the larval ECG recording system for characterisation of a cardiac mutant (cacna1c sa6050) was demonstrated through a set of drug treatments and demonstration of drug discovery through ECG analysis of chemical rescue of the mutant phenotype.

Overall, the results presented highlight the zebrafish as an effective, robust and reliable model for cardiac arrhythmia and assessing drug responses in vivo.

Type of Work: Thesis (Doctorates > Ph.D.)
Award Type: Doctorates > Ph.D.
College/Faculty: Colleges (2008 onwards) > College of Medical & Dental Sciences
School or Department: Institute of Cancer and Genomic Sciences
Funders: British Heart Foundation
Subjects: Q Science > Q Science (General)


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