Abstract

During developmental stages, biomechanical stimuli on cardiac cells modulate genetic programs, and deviations from normal stimuli can lead to cardiac defects. Therefore, it is important to characterize normal cardiac biomechanical stimuli during early developmental stages. Using the chicken embryo model of cardiac development, we focused on characterizing biomechanical stimuli on the Hamburger–Hamilton (HH) 18 chick cardiac outflow tract (OFT), the distal portion of the heart from which a large portion of defects observed in humans originate. To characterize biomechanical stimuli in the OFT, we used a combination of in vivo optical coherence tomography (OCT) imaging, physiological measurements and computational fluid dynamics (CFD) modeling. We found that, at HH18, the proximal portion of the OFT wall undergoes larger circumferential strains than its distal portion, while the distal portion of the OFT wall undergoes larger wall stresses. Maximal wall shear stresses were generally found on the surface of endocardial cushions, which are protrusions of extracellular matrix onto the OFT lumen that later during development give rise to cardiac septa and valves. The non-uniform spatial and temporal distributions of stresses and strains in the OFT walls provide biomechanical cues to cardiac cells that likely aid in the extensive differential growth and remodeling patterns observed during normal development.

Highlights

  • IntroductionBlood flow is essential for normal cardiac development [1,2]

  • During early developmental stages, blood flow is essential for normal cardiac development [1,2]

  • We focused here on the chick cardiac outflow tract (OFT), the distal portion of the heart connecting the primitive ventricle to the arterial system, at an early stage of development, Hamburger– Hamilton (HH) 18 (,3 days of incubation)

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Summary

Introduction

Blood flow is essential for normal cardiac development [1,2]. Cardiac cells are subjected to biomechanical stimuli (stresses and strains) that depend on the interaction between blood flow and heart tissues. These biomechanical stimuli modulate cardiac cellular functions and cardiac development. While cardiac defects can have a genetic origin, it is likely that a large portion of congenital heart defect cases is due to environmental factors, such as alterations of blood flow conditions during early stages of development. To better understand how blood flow conditions affect cardiac development, it is critical to characterize the biomechanical stimuli to which cardiac cells are subjected during development

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