Vortex Dynamics in Trabeculated Embryonic Ventricles.

Nicholas Battista,Andrea Lane,Dylan Douglas,Jiandong Liu,Leigh Samsa,Laura Miller

doi:10.3390/jcdd6010006

Abstract

Proper heart morphogenesis requires a delicate balance between hemodynamic forces, myocardial activity, morphogen gradients, and epigenetic signaling, all of which are coupled with genetic regulatory networks. Recently both in vivo and in silico studies have tried to better understand hemodynamics at varying stages of veretebrate cardiogenesis. In particular, the intracardial hemodynamics during the onset of trabeculation is notably complex—the inertial and viscous fluid forces are approximately equal at this stage and small perturbations in morphology, scale, and steadiness of the flow can lead to significant changes in bulk flow structures, shear stress distributions, and chemical morphogen gradients. The immersed boundary method was used to numerically simulate fluid flow through simplified two-dimensional and stationary trabeculated ventricles of 72, 80, and 120 h post fertilization wild type zebrafish embryos and ErbB2-inhibited embryos at seven days post fertilization. A 2D idealized trabeculated ventricular model was also used to map the bifurcations in flow structure that occur as a result of the unsteadiness of flow, trabeculae height, and fluid scale (). Vortex formation occurred in intertrabecular regions for biologically relevant parameter spaces, wherein flow velocities increased. This indicates that trabecular morphology may alter intracardial flow patterns and hence ventricular shear stresses and morphogen gradients. A potential implication of this work is that the onset of vortical (disturbed) flows can upregulate Notch1 expression in endothelial cells in vivo and hence impacts chamber morphogenesis, valvulogenesis, and the formation of the trabeculae themselves. Our results also highlight the sensitivity of cardiac flow patterns to changes in morphology and blood rheology, motivating efforts to obtain spatially and temporally resolved chamber geometries and kinematics as well as the careful measurement of the embryonic blood rheology. The results also suggest that there may be significant changes in shear signalling due to morphological and mechanical variation across individuals and species.

Highlights

Since the developing heart and embryo continue to function for some time in the absence of erythrocytes, it appears that the function of the early embryonic heart is not for the purpose of nutrient transport [1,2]
The cases with biologically realistic geometries were of WT zebrafish and an ErbB2-inhibited mutant to contrast the intracardial and intertrabecular fluid dynamics of an embryonic zebrafish heart during development
Two-dimensional immersed boundary simulations were used to solve for the flow fields within both biologically realistic geometries (3 dpf, 80 hpf, two 5 dpf WT zebrafish and a 7 dpf ErbB2-inhibited zebrafish from [21]) and idealized models of trabeculated ventricles

Summary

Introduction

Since the developing heart and embryo continue to function for some time in the absence of erythrocytes, it appears that the function of the early embryonic heart is not for the purpose of nutrient transport [1,2]. Two important roles for intracardial fluid dynamics in terms of proper cardiogenesis are to exert hemodynamic forces onto the ventricular lining and to advect morphogens [2,6] These two fluid effects help regulate and drive organogenesis in developing embryos. Both shear stress and pressure may be key components to activating developmental regulatory networks by acting on cardiac cells [7] through a process called mechanotransduction. Increased receptor–ligand bond formation may appear near the endothelial lining in regions of higher vorticity [8], which gives rise to greater mixing of chemical morphogens These chemicals may act as epigenetic signals, which are advected throughout the chamber [9,10]. It is clear that irregular hemodynamics leads to cardiomyopathies or embryonic death [3,11,12,13,14]

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