The Fluid Dynamics of Heart Development: The effect of morphology on flow at several stages Public Deposited

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  • March 21, 2019
Creator
  • Battista, Nicholas
    • Affiliation: College of Arts and Sciences, Department of Mathematics
Abstract
  • Proper cardiogenesis requires a delicate balance between genetic and environmental (epigenetic) signals, and mechanical forces. While many cellular biologists and geneticists have extensively studied heart morphogenesis using various experimental techniques, only a few scientists have begun using mathematical modeling as a tool for studying cardiogenic events. Hemodynamic processes, such as vortex formation, are important in the generation of shear at the endothelial surface layer and strains at the epithelial layer, which aid in proper morphology and functionality. The purpose of this thesis is to study the underlying fluid dynamics in various stages on heart development, in particular, the morphogenic stages when the heart is a linear heart tube as well as during the onset of ventricular trabeculation. Previous mathematical models of the linear heart tube stage have focused on mechanisms of valveless pumping, whether dynamic suction pumping (impedance pumping) or peristalsis; however, they all have neglected hematocrit. The impact of blood cells was examined by fluid-structure interaction simulations, via the immersed boundary method. Moreover, electrophysiology models were incorporated into an immersed boundary framework, and bifurcations within the morphospace were studied that give rise to a spectrum of pumping regimes, with peristaltic-like waves of contraction and impedance pumping at the extremes. Lastly, effects of resonant pumping, damping, and boundary inertial effects (added mass) were studied for dynamic suction pumping. The other stage of heart development considered here is during the onset of ventricular trabeculation. This occurs after the heart has undergone the cardiac looping stage and now is a multi-chambered pumping system with primitive endocardial cushions, which act as precursors to valve leaflets. Trabeculation introduces complex morphology onto the inner lining of the endocardium in the ventricle. This transition of a smooth endocardium to one with complex geometry, may have significant effect on the intracardial fluid dynamics and stress distribution within emrbyonic hearts. Previous studies have not included these geometric perturbations along the ventricular endocardium. The role of trabeculae on intracardial (and intertrabecular) flows was studied using two different mathematical models implemented within an immersed boundary framework. It is shown that the trabecular geometry and number density have a significant effect on such flows. Furthermore this thesis also focused attention to the creation of software for scientists and engineers to perform fluid-structure interaction simulations at an accelerated rate, in user-friendly environments for beginner programmers, e.g., MATLAB or Python 3.5. The software, IB2d, performs fully coupled fluid-structure interaction problems using Charles Peskin's immersed boundary method. IB2d is capable of running a vast range of biomechanics models and contains multiple options for constructing material properties of the fiber structure, advection-diffusion of a chemical gradient, muscle mechanics models, Boussinesq approximations, and artificial forcing to drive boundaries with a preferred motion. The software currently contains over 50 examples, ranging from rubber-bands oscillating to flow past a cylinder to a simple aneurysm model to falling spheres in a chemical gradient to jellyfish locomotion to a heart tube pumping coupled with electrophysiology, muscle, and calcium dynamics models
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Rights statement
  • In Copyright
Advisor
  • Klotsa, Daphne
  • Liu, Jiandong
  • Forest, M. Gregory
  • Miller, Laura
  • Griffith, Boyce
Degree
  • Doctor of Philosophy
Degree granting institution
  • University of North Carolina at Chapel Hill Graduate School
Graduation year
  • 2017
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