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Stress, structure, and function of the embryonic heart

dc.contributor.authorGendernalik, Alex L., author
dc.contributor.authorBark, David, advisor
dc.contributor.authorGarrity, Deborah, committee member
dc.contributor.authorPuttlitz, Christian, committee member
dc.contributor.authorHeyliger, Paul, committee member
dc.date.accessioned2023-06-01T23:56:08Z
dc.date.available2023-06-01T23:56:08Z
dc.date.issued2023
dc.descriptionIncludes bibliographical references.
dc.description2023 Spring.
dc.description.abstractEmbryonic heart development is a complex process that requires the coordination of hemodynamic stress and tissue morphogenesis. Improperly timed or distorted mechanical cues can cause reverberating malformations that result in congenital heart defects (CHDs) or embryo death. CHDs occur in ~1% of live births. Only ~20% have a known genetic origin. Altered mechanical signaling or hemodynamics is likely a common contributor to CHD prevalence. Significant research using animal models has shown that altered hemodynamics causes varied malformations. Mechanical properties describe the underlying tissue architecture, which dictates how the heart transmits and reacts to stress. This work aims to quantify and map the mechanical properties to understand how they direct the formation of specific heart structures and function. Furthermore, we seek to understand how mechanical properties change in response to altered hemodynamics. We hypothesize that mechanical properties indicate regions of eventual structure formation, are sensitive to altered hemodynamics, and dictate the pumping method that the heart uses to drive blood flow. We test this hypothesis through three aims. In aim 1, we describe a novel technique in which we use controlled pressurization to deform the embryonic zebrafish heart. We measure deformation in two-dimensions and identify constitutive models of the embryonic heart tissue. Finite element analysis is used to validate our findings in three dimensions. In this aim, we establish that controlled pressurization is a valid technique for inducing measured deformation of the heart. Through this, we determine that the zebrafish myocardial stiffness is on the order of 10 kPa. In aim 2, we further develop our pressurization technique by measuring deformation in three dimensions using confocal microscopy. Furthermore, we use a morpholino antisense oligonucleotide (MO), gata1, to alter embryonic zebrafish heart hemodynamics by blocking development of red blood cells, thus decreasing the viscosity and arterial pressure based on Poiseuille's law. Upon mapping strain in three dimensions, we find that strain throughout the heart is variable, with specific regions of low and high strain from 2 to 3 days post-fertilization (dpf). Low arterial pressure in gata1 MO embryos resulted in significantly increased strain compared to controls, indicating that altered hemodynamics cause altered mechanical properties in the developing embryonic heart. In aim 3, we seek to determine if the zebrafish early embryonic heart tube drives blood flow through peristalsis or impedance-type pumping. We attempt to directly induce impedance pumping by cannulating the atrial inlet of the heart tube after halting contractions and applying a controlled pressure pulse. Additionally, we use precisely controlled temperatures to increase heart rate, thus increasing arterial pressure. As temperature is increased, we use high speed imaging to analyze the contractile motion and resulting blood flow in the tube heart. Furthermore, we describe a previously unknown response whereby the traveling endocardial closure shortens with increased arterial pressure. In this aim, we fail to find evidence of impedance-type pumping but cannot preclude it contributes to blood flow. In summary, our pressurization technique can be used to map strain in the zebrafish embryonic heart; altering hemodynamics by reducing arterial pressure results in decreased stiffness of the embryonic heart myocardium, and endocardial closure length in the embryonic zebrafish heart tube shortens as arterial pressure and heart rate increase.
dc.format.mediumborn digital
dc.format.mediumdoctoral dissertations
dc.identifierGendernalik_colostate_0053A_17728.pdf
dc.identifier.urihttps://hdl.handle.net/10217/236698
dc.languageEnglish
dc.language.isoeng
dc.publisherColorado State University. Libraries
dc.relation.ispartof2020-
dc.rightsCopyright and other restrictions may apply. User is responsible for compliance with all applicable laws. For information about copyright law, please see https://libguides.colostate.edu/copyright.
dc.subjectheart
dc.subjectmechanical
dc.subjectzebrafish
dc.subjectmaterial
dc.subjectembryonic
dc.subjectproperties
dc.titleStress, structure, and function of the embryonic heart
dc.typeText
dcterms.rights.dplaThis Item is protected by copyright and/or related rights (https://rightsstatements.org/vocab/InC/1.0/). You are free to use this Item in any way that is permitted by the copyright and related rights legislation that applies to your use. For other uses you need to obtain permission from the rights-holder(s).
thesis.degree.disciplineBiomedical Engineering
thesis.degree.grantorColorado State University
thesis.degree.levelDoctoral
thesis.degree.nameDoctor of Philosophy (Ph.D.)

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