New Models for Assessing Effects of Contractility

DESCRIPTION (provided by applicant): Cardiotoxicity is the leading cause of drug withdrawal, and is a major reason for delays or failure during clinical trials. Recently Vioxx, a widely used anti-arthritic drug, was removed from the market due to increased risk of heart attack and stroke. Other drugs such as terfenadine, grepafloxacin and cisapride were also removed from the U.S. market due to serious cardiac toxicity. Drug cardiotoxicity represents a serious threat both to patient safety and to the financi al stability of the biopharmaceutical industry. The aim of this research is to establish zebrafish as an in vivo preclinical model to assess cardiac contractility after drug treatment by measuring cardiac blood volume and blood pressure. This zebrafish scr een will streamline the drug development time-line, prioritize drug candidates for animal testing, and reduce unnecessary costs for mammalian studies. This convenient animal model will serve as an intermediate step between cell-based evaluation and convent ional animal testing. PUBLIC HEALTH RELEVANCE: The aim of this research is to establish zebrafish as an in vivo preclinical model to assess cardiac contractility after drug treatment by measuring cardiac blood volume and blood pressure.