A major concern regarding drugs in development is cardiac toxicity. Commonly, drugs in development can cause changes to cardiac contractility, the force with which the heart beats, and cardiac rhythmicity, resulting in toxic side effects. The purpose of this Phase 1 proposal is to develop zebrafish assays for measuring drug-induced changes in cardiac contractility and cardiac rhythmicity. These assays will be developed using a transgenic zebrafish line expressing a green fluorescent reporter protein specifically in the heart. Methods of assessing contractility and rhythmicity in zebrafish will be developed. Drugs that are known to cause changes to cardiac contractility and rhythmicity in humans will be tested using these zebrafish in order to validate the assay. Development of these assays will allow high-throughput, in vivo testing of drugs in development for cardiac toxicity.
Thesaurus Terms: adrenergic agent, beta antiadrenergic agent, calcium channel blocker, cardiac glycoside, cardiotoxin, drug adverse effect, drug screening /evaluation, heart contraction, heart rhythm, high throughput technology, phosphodiesterase inhibitor, technology /technique development zebrafish
