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Thrombosis is a leading cause of death and the development of effective and safe therapeutic agents for thrombotic diseases has been proven challenging. In this study, taking advantage of the transparency of larval zebrafish, we developed a larval zebrafish thrombosis model for drug screening and efficacy assessment. Zebrafish at 2 dpf (days post fertilization) were treated with phenylhydrazine (PHZ) and a testing drug for 24 h. Tested drugs were administered into the zebrafish either by direct soaking or circulation microinjection. Antithrombotic efficacy was quantitatively evaluated based on our previously patented technology characterized as an image analysis of the heart red blood cells stained with O-dianisidine staining. Zebrafish at 2 dpf treated with PHZ at a concentration of 1.5 μM for a time period of 24 h were determined as the optimum conditions for the zebrafish thrombosis model development. Induced thrombosis in zebrafish was visually confirmed under a dissecting stereomicroscope and quantified by the image assay. All 6 human antithrombotic drugs (aspirin, clopidogrel, diltiazem hydrochloride injection, xuanshuantong injection, salvianolate injection, and astragalus injection) showed significant preventive and therapeutic effects on zebrafish thrombosis (p < 0.05, p < 0.01, & p < 0.001) in this zebrafish thrombosis model. The larval zebrafish thrombosis model developed and validated in this study could be used for in vivo thrombosis studies and for rapid screening and efficacy assessment of antithrombotic drugs.

Heart failure is a leading cause of death and the development of effective and safe therapeutic agents for heart failure has been proven challenging. In this study, taking advantage of larval zebrafish, we developed a zebrafish heart failure model for drug screening and efficacy assessment. Zebrafish at 2 dpf (days postfertilization) were treated with verapamil at a concentration of 200 μM for 30 min, which were determined as optimum conditions for model development. Tested drugs were administered into zebrafish either by direct soaking or circulation microinjection. After treatment, zebrafish were randomly selected and subjected to either visual observation and image acquisition or record videos under a Zebralab Blood Flow System. The therapeutic effects of drugs on zebrafish heart failure were quantified by calculating the efficiency of heart dilatation, venous congestion, cardiac output, and blood flow dynamics. All 8 human heart failure therapeutic drugs (LCZ696, digoxin, irbesartan, metoprolol, qiliqiangxin capsule, enalapril, shenmai injection, and hydrochlorothiazide) showed significant preventive and therapeutic effects on zebrafish heart failure (p < 0.05, p < 0.01, and p < 0.001) in the zebrafish model. The larval zebrafish heart failure model developed and validated in this study could be used for in vivo heart failure studies and for rapid screening and efficacy assessment of preventive and therapeutic drugs.

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