Download Hemodynamic frequency content regulates valvulogenesis

Hemodynamic frequency content regulates valvulogenesis
Mechanotransduction of blood flow forces plays a major role in cardiac
development. However, studies of the fluid dynamics of the developing heart are
still spars. Zebrafish is an ideal model in this context. It is transparent, and blood
flow and heart contraction can be perturbed by means of several non-invasive
genetic tools. However, a detailed characterization of the underling mechanical
cues is missing.
In order to fill this gap, we propose an in-silico model for a detailed
characterization of the biomechanics of the zebrafish heart.
Since the Reynolds number in the zebrafish heart is well below one, we can
predict blood flow by solving the Stokes flow equations with efficient and
newly developed boundary methods. The computational domain for our
simulations is based on fast confocal imaging of the live beating heart and
dedicated segmentation programs. The dynamics of the reconstructed cardiac
wall is analysed to characterise the contraction pattern and to obtain the velocity
boundary conditions for our simulations.
In an attempt to identify the relevant mechanical cues leading to valvulogenesis,
we compute the frequency content of the flow shear stress at the endocardial
cells of controls and those of morphants with valve defects and perturbed
hemodynamics.
Our results bring evidences that the oscillatory content of the shear stress, and in
particular its fundamental frequency, modulates the mechanotransduction
process leading to valvulogenesis. !
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