A Zebrafish Heart Failure Model for Assessing Therapeutic Agents

Area of Science:

• Cardiovascular Research
• Pharmacology
• Zebrafish Models

Background:

• Heart failure remains a major cause of mortality, posing significant challenges in developing effective and safe treatments.
• Existing therapeutic strategies for heart failure require continuous innovation and validation.

Purpose of the Study:

• To develop and validate a novel larval zebrafish heart failure model for efficient drug screening and efficacy assessment.
• To evaluate the therapeutic potential of established human heart failure drugs using the developed zebrafish model.

Main Methods:

• Larval zebrafish (2 days postfertilization) were induced into a heart failure state using optimized verapamil treatment (200 μM for 30 min).
• Drugs were administered via direct soaking or microinjection, with therapeutic effects quantified by assessing heart dilatation, venous congestion, cardiac output, and blood flow dynamics.
• High-throughput screening was facilitated by visual observation, image acquisition, and video recording using a Zebralab Blood Flow System.

Main Results:

• The developed larval zebrafish model demonstrated significant responses to heart failure induction.
• All eight tested human heart failure drugs (LCZ696, digoxin, irbesartan, metoprolol, qiliqiangxin capsule, enalapril, shenmai injection, hydrochlorothiazide) exhibited significant preventive and therapeutic effects (p < 0.05, p < 0.01, p < 0.001).
• The model successfully quantified drug efficacy through measurable cardiovascular parameters.

Conclusions:

• The validated larval zebrafish heart failure model offers a robust platform for in vivo studies of heart failure.
• This model enables rapid screening and efficacy assessment of potential preventive and therapeutic agents for heart failure.
• The findings support the utility of zebrafish as a preclinical model for cardiovascular drug development.