4-D Computational Modeling of Cardiac Outflow Tract Hemodynamics over Looping Developmental Stages in Chicken Embryos

Abstract

Cardiogenesis is interdependent with blood flow within the embryonic system. Recently, a number of studies have begun to elucidate the effects of hemodynamic forces acting upon and within cells as the cardiovascular system begins to develop. Changes in flow are picked up by mechanosensors in endocardial cells exposed to wall shear stress (the tangential force exerted by blood flow) and by myocardial and mesenchymal cells exposed to cyclic strain (deformation). Mechanosensors stimulate a variety of mechanotransduction pathways which elicit functional cellular responses in order to coordinate the structural development of the heart and cardiovascular system. The looping stages of heart development are critical to normal cardiac morphogenesis and have previously been shown to be extremely sensitive to experimental perturbations in flow, with transient exposure to altered flow dynamics causing severe late stage cardiac defects in animal models. This paper seeks to expand on past research and to begin establishing a detailed baseline for normal hemodynamic conditions in the chick outflow tract during these critical looping stages. Specifically, we will use 4-D (3-D over time) optical coherence tomography to create in vivo geometries for computational fluid dynamics simulations of the cardiac cycle, enabling us to study in great detail 4-D velocity patterns and heterogeneous wall shear stress distributions on the outflow tract endocardium. This information will be useful in determining the normal variation of hemodynamic patterns as well as in mapping hemodynamics to developmental processes such as morphological changes and signaling events during and after the looping stages examined here.

Characterisation of the developing heart in a pressure overloaded model utilising RNA sequencing to direct functional analysis

“…Environmental and genetic factors affect embryonic heart formation, with blood flow playing a critical role in cardiac remodelling (Midgett & Rugonyi, ; Courchaine et al ). Though many haemodynamically altered heart models exist in the literature (Sedmera et al ; Tomanek et al ; Miller et al ; Buffinton et al ; Chivukula et al ; Midgett et al ), a global molecular characterisation of whole hearts during cardiogenesis has not been performed.…”

“…According to the British Heart Foundation, congenital heart defects are found in at least one in every 180 births in the UK (http://www.bhf.org.uk), with cardiomyopathies accounting for 8–11% of those diagnosed with a defect (Pedra et al ). Both environmental and genetic factors affect embryonic heart formation, with blood flow playing a critical role in cardiac remodelling (Midgett & Rugonyi, ; Midgett et al ; Courchaine et al ). Animal models of haemodynamic alteration have been found to have phenotypes similar to those seen in human heart disorders, with features of cardiomyopathy (Sedmera et al ; Midgett & Rugonyi, ; Midgett et al ).…”

Computational Modeling of Blood Flow Hemodynamics for Biomechanical Investigation of Cardiac Development and Disease

“…AV canal, OFT, and aortic arch are the mostly investigated regions in chicken embryo CFD models [ 38 , 89 , 96 , 97 , 98 , 99 , 100 ]. Numerical investigations can be categorized as the studies examining normal cardiac development and studies investigating the development after external interventions.…”

“…With the development of medical imaging techniques, detailed geometric models can be generated for human fetal hearts [ 35 ], chicken and zebrafish embryos [ 36 , 37 , 38 , 39 ]. Although there are some challenges in imaging the highly dynamic heart tissues, it is possible to generate four dimensional (4D) models, including three dimensions in space and one dimension in time domain [ 40 ].…”

New Concepts in the Development and Malformation of the Arterial Valves

“…It is possible that this localised NCC aggregation could be directed by signals from the surrounding myocardium or endothelium, however, it seems more likely that this is dictated by the physical properties of vorticial blood flow through the looping, but as yet unseptated, heart tube. Indeed, it has been shown that shear stress is asymmetrically localised in the outflow wall as the cushions are beginning to cellularise [ 13 ]; this could help to position and/or stabilise the cellularising cushions within the circumference of the outflow tract ([ 12 ]; Figure 2 A). Later, the fusion of these spiralling cushions leads to placing of the root of the aorta to the left of the pulmonary trunk.…”