The role of biomechanics in the formation and function of cardiac trabeculae in zebrafish embryonic hearts
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Author(s)
Cairelli, Adriana Gaia
Type
Thesis
Abstract
Cardiac trabeculae are uneven ventricular muscular structures developing during early
embryonic heart development at the outer ventricular curvature. The development of these structures
is a mechanosensitive process, where specific forces are needed for the correct formation, and
abnormal mechanical stimuli can lead to malformations and eventually embryonic death. It is
important to understand the nature of the embryonic heart forces, both fluid and wall tissue stimuli,
which were not well characterized. Fluid stimuli are very sensitive to fine-scale geometry and motion
dynamics of the trabecular structures, and past studies have not provided sufficient considerations to
these fine details. Similarly, cardiac wall tissue stresses are not well-investigated and it remains
unclear if these structures can confer any biomechanical advantage to the cardiac function. The aim
of this thesis is, thus, to improve our understanding of the biomechanics of cardiac trabeculae, to
comprehend their role in the formation and function of the embryonic heart.
My fluid-dynamics results showed that the squeezing motion of inter-trabecular spaces is the main
mechanism responsible for endocardial wall shear stress (WSS) stimuli, but neither the WSS
magnitude nor the oscillatory nature of WSS could distinguish the trabeculated and non-trabeculated
regions in the ventricle: other factors on top of flow may be needed to stimulate trabecular formation.
My solid-mechanics results suggest three functions for cardiac trabeculae: enhancing tissue
deformability to facilitate cardiac pumping actions, countering high myocardial stresses with active
tension while reducing myocardial stresses as structural support, and reducing spatial inhomogeneity
of tissue stiffness. I further discovered that low myocardial stresses could prevent the formation of
trabeculae, but drug-induced restoration of stresses can rescue their formation, suggesting the
importance of tissue stresses to the formation of trabeculae.
In conclusion, a complex multi-component consideration is needed to understand the
biomechanics around the cardiac trabeculae in zebrafish embryonic hearts.
embryonic heart development at the outer ventricular curvature. The development of these structures
is a mechanosensitive process, where specific forces are needed for the correct formation, and
abnormal mechanical stimuli can lead to malformations and eventually embryonic death. It is
important to understand the nature of the embryonic heart forces, both fluid and wall tissue stimuli,
which were not well characterized. Fluid stimuli are very sensitive to fine-scale geometry and motion
dynamics of the trabecular structures, and past studies have not provided sufficient considerations to
these fine details. Similarly, cardiac wall tissue stresses are not well-investigated and it remains
unclear if these structures can confer any biomechanical advantage to the cardiac function. The aim
of this thesis is, thus, to improve our understanding of the biomechanics of cardiac trabeculae, to
comprehend their role in the formation and function of the embryonic heart.
My fluid-dynamics results showed that the squeezing motion of inter-trabecular spaces is the main
mechanism responsible for endocardial wall shear stress (WSS) stimuli, but neither the WSS
magnitude nor the oscillatory nature of WSS could distinguish the trabeculated and non-trabeculated
regions in the ventricle: other factors on top of flow may be needed to stimulate trabecular formation.
My solid-mechanics results suggest three functions for cardiac trabeculae: enhancing tissue
deformability to facilitate cardiac pumping actions, countering high myocardial stresses with active
tension while reducing myocardial stresses as structural support, and reducing spatial inhomogeneity
of tissue stiffness. I further discovered that low myocardial stresses could prevent the formation of
trabeculae, but drug-induced restoration of stresses can rescue their formation, suggesting the
importance of tissue stresses to the formation of trabeculae.
In conclusion, a complex multi-component consideration is needed to understand the
biomechanics around the cardiac trabeculae in zebrafish embryonic hearts.
Version
Open Access
Date Issued
2023-08
Date Awarded
2024-02
Copyright Statement
Creative Commons Attribution NonCommercial Licence
License URL
Advisor
Yap, Choon Hwai
Publisher Department
Bioengineering
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)