Esketamine Exposure Impairs Cardiac Development and Function in Zebrafish Larvae.

Area of Science:

• Cardiovascular toxicology
• Developmental biology
• Pharmacology

Background:

• Esketamine is a common intravenous anesthetic.
• Its cardiac safety profile, especially during development, requires further investigation.

Purpose of the Study:

• To investigate the effects of esketamine on zebrafish embryonic heart development and function.
• To elucidate the molecular mechanisms underlying esketamine-induced cardiotoxicity.

Main Methods:

• Zebrafish embryos were exposed to varying concentrations of esketamine (1, 10, 100 mg/L) from 48 to 72 hours post-fertilization.
• Cardiac function (heart rate, stroke volume, cardiac output) and gene expression related to cardiac development and calcium signaling were analyzed.
• Acetylcholine concentration was measured in exposed embryos.

Main Results:

• Esketamine exposure led to increased hatching rates, decreased heart rate, stroke volume, and cardiac output.
• Ventricular dilation and atrial wall thickening were observed in transgenic zebrafish.
• Abnormal expression of key cardiac development genes (e.g., nkx2.5, gata4) and calcium signaling genes (e.g., ry r2a, atp2a2a) was detected.
• Increased acetylcholine concentration was noted.

Conclusions:

• Esketamine exposure negatively impacts zebrafish embryonic cardiac development and function.
• The anesthetic may impair cardiac neural regulation by altering acetylcholine levels.
• Findings highlight the need for thorough safety evaluations of esketamine's cardiovascular effects.