Simulating the Hemodynamic Environment in the Zebrafish Embryonic Heart in Four Dimensions

Yoke Yin Foo1, Shuhao Shen1, Huiping, Shermaine Tay2, Nurgul Imangali2, Martin Buist1, Nanguang Chen1, Christoph Winkler2, Choon Hwai Yap1
1Department of Biomedical Engineering, National University of Singapore, 2Department of Biological Science, National University of SIngapore


Abstract

Introduction: Recent studies suggested that proper blood flow plays a pivotal role in the early stage of heart development and in congenital heart malformations, underlying the importance of understanding the fluid mechanical environment of the embryonic heart. This study aims to perform an in-depth study of fluid mechanics in several normal 5 days post-fertilization (dpf) zebrafish embryonic ventricles via image-based computational fluid dynamics (CFD) simulation.

Methods: Several embryos from a transgenic line, Tg(phiC31.attP.2A, -0.8myl7: EGFP), which marks the myocardium with GFP, were investigated. The embryonic hearts were imaged with a custom-built line-scanning focal-modulation microscope at 5 dpf. Dynamic-mesh CFD was performed in ANSYS via a mathematical model of ventricular wall motion.

Results: The zebrafish hearts exhibited a wave-like motion, where systolic contraction and diastolic relaxation started near the inlet and spread like a wave to the outlet, a configuration that is shown to be flow energy efficient, but the absence of pressure and velocity waves rule out impedance pumping mechanism. Inflow velocities were higher near the inlet and smaller at the outlet, and vice-versa for outflow velocities. Consequently, wall shear stress (WSS) waveforms at the near inlet region were interestingly out of phase with those at the near outlet region. Large spatial variations of WSS was observed.

Conclusion: We characterized the fine details of fluid dynamics in the zebrafish embryonic heart at 5 dpf. Data serves as benchmark for disease model to be compared to. The embryonic ventricle exhibited energy efficient wave-like contractile motion and substantial spatial variability in WSS.