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pyHeart4Fish: Chamber-specific heart phenotype quantification of zebrafish in high-content screens
Viviana L Vedder1,2,3, Tobias Reinberger1,2,3, Syed M I Haider1,2,3
1Institute for Cardiogenetics, University of Lübeck, Lübeck, Germany.
Insights
A new tool, pyHeart4Fish, analyzes zebrafish heart development. The study screened 1,280 drugs, finding 10.5% affected heart rate and identifying specific cardiotoxic compounds and defects.
Area of Science:
- Cardiovascular research
- Developmental toxicology
- Pharmacology
Background:
- Congenital heart diseases are common, and drug exposure can cause abnormalities.
- The developmental toxicity of many approved drugs remains understudied.
- Zebrafish are a valuable model for studying cardiovascular diseases and drug toxicity.
Purpose of the Study:
- To develop an open-access tool for quantifying cardiac phenotypes in zebrafish.
- To screen a library of 1,280 compounds for cardiotoxicity during embryonic development.
- To identify specific drugs that induce cardiovascular defects and arrhythmias.
Main Methods:
- Developed pyHeart4Fish, a Python-based tool with a GUI for automated cardiac analysis in zebrafish.
- Conducted a high-content drug screen of 1,280 compounds on zebrafish embryos.
- Quantified heart rate, contractility, and arrhythmia scores at 2 days post-fertilization.
Main Results:
- Approximately 10.5% of tested drugs significantly impacted heart rate at 20 µM.
- Identified teratogenic effects of pregnenolone and contractility defects in seven compounds.
- Detected arrhythmias, including atrioventricular block and atrial flutter, induced by specific drugs.
Conclusions:
- pyHeart4Fish is a novel, open-access tool for comprehensive cardiac analysis in zebrafish.
- The study identified numerous compounds with potential cardiotoxic effects on developing embryos.
- This research provides valuable data for understanding drug-induced developmental cardiovascular toxicity.
Abstract:
Cardiovascular diseases (CVDs) are the leading cause of death. Of CVDs, congenital heart diseases are the most common congenital defects, with a prevalence of 1 in 100 live births. Despite the widespread knowledge that prenatal and postnatal drug exposure can lead to congenital abnormalities, the developmental toxicity of many FDA-approved drugs is rarely investigated. Therefore, to improve our understanding of drug side effects, we performed a high-content drug screen of 1,280 compounds using zebrafish as a model for cardiovascular analyses. Zebrafish are a well-established model for CVDs and developmental toxicity. However, flexible open-access tools to quantify cardiac phenotypes are lacking. Here, we provide pyHeart4Fish, a novel Python-based, platform-independent tool with a graphical user interface for automated quantification of cardiac chamber-specific parameters, such as heart rate (HR), contractility, arrhythmia score, and conduction score. In our study, about 10.5% of the tested drugs significantly affected HR at a concentration of 20 µM in zebrafish embryos at 2 days post-fertilization. Further, we provide insights into the effects of 13 compounds on the developing embryo, including the teratogenic effects of the steroid pregnenolone. In addition, analysis with pyHeart4Fish revealed multiple contractility defects induced by seven compounds. We also found implications for arrhythmias, such as atrioventricular block caused by chloropyramine HCl, as well as (R)-duloxetine HCl-induced atrial flutter. Taken together, our study presents a novel open-access tool for heart analysis and new data on potentially cardiotoxic compounds.
