Quantifying Cardiovascular Flow Dynamics During Early Development

Abstract

ABSTRACT:The relationship between developing biologic tissues and their dynamic fluid environments is intimate and complex. Increasing evidence supports the notion that these embryonic flowstructure interactions influence whether development will proceed normally or become pathogenic. Genetic, pharmacological, or surgical manipulations that alter the flow environment can thus profoundly influence morphologic and functional cardiovascular phenotypes. Functionally deficient phenotypes are particularly poorly described as there are few imaging tools with sufficient spatial and temporal resolution to quantify most intra-vital flows. The ability to visualize biofluids flow in vivo would be of great utility in functionally phenotyping model animal systems and for the elucidation of the mechanisms that underlie flow-related mechano-sensation and transduction in living organisms. This review summarizes the major methodological advances that have evolved for the quantitative characterization of intra-vital fluid dynamics with an emphasis on assessing cardiovascular flows in vertebrate model organisms. ROLE OF FLUID FLOW IN DEVELOPMENTI n addition to facilitating convective transport, intra-vital fluid flows impose substantial mechanical stresses on adjacent and underlying cells. These flow-induced forces are widely acknowledged as critical to the proper development and maintenance of many aspects of biologic form and function. This is particularly true during embryogenesis where internally-derived, flow-related forces are thought to be morphogens influencing a number of key developmental processes including; symmetry determination (1,2), cardiogenesis (3-5), blood vessel formation (6,7), glomerulogenesis (8), brain development (9), and lung development (10,11). In addition to their roles during normal development, the biomechanical forces generated by aberrant intra-vital flow have been implicated as important factors in the pathogenesis of a variety of diseases in the cardiovascular (12-14), nervous (15-17), and renal (18 -20) systems.The specific mechanisms by which living cells sense, transduce and respond to flow-induced stresses are only partially known (21-25). In vitro studies have contributed a great deal to our understanding of these signaling pathways in general, and how cardiovascular endothelial cells, the flow sensors and transducers lining the vascular walls, react to shear stress (26 -29), stretch (30,31), and pressure (32,33). Of these, wall shear stress has received the most attention as both its magnitude and orientation are thought to play roles during vascular development. Fluid shear stresses occur within the cardiovascular system as blood flows tangentially to the surrounding vessel wall. This frictional force is defined by the product of the shear rate (derivative of velocity with respect to the vessel radius) and the dynamic viscosity of blood. To reconcile the complex velocity gradients that exist within a pulsing, flexible heart tube filled with a moving, non-Newtonian fluid we need to obtain s...

4D subject-specific inverse modeling of the chick embryonic heart outflow tract hemodynamics

“…Initiation, formation and subdivision of the heart are genetically controlled processes (Brand 2003; Srivastava 2006; Bruneau 2008); however, blood flow plays a critical role in regulating cardiac development by providing hemodynamic stimuli (such as blood pressure and wall shear stress) to cardiac tissues. These mechanical stimuli modulate development through mechanotransduction mechanisms (Hogers et al 1997; Loots et al 2003; Azhar et al 2003; Bartman and Hove 2005; Groenendijk et al 2005; Hove 2006; Groenendijk et al 2007; Egorova et al 2011; Ten Dijke et al 2012; Lim and Thiery 2012; Goetz et al 2014). Using animal models, it has been shown that altering cardiac blood flow during early development leads to congenital heart defects resembling those seen in humans (Clark and Rosenquist 1977; Sedmera et al 1997; Vos et al 2003; Miller et al 2003; Granados-Riveron and Brook 2012; Midgett et al 2014).…”

“…Methodologies employed to measure embryonic blood flow dynamics range from particle image velocity (PIV) to Doppler techniques. Using micro PIV (μPIV) (Jones et al 2004; Vennemann et al 2006; Hove 2006; Milan et al 2006), either red blood cells or particles inserted in the circulation are followed over time with a series of images that allow localization and tracking of specific particles and hence localized quantification of blood flow velocities. PIV and μPIV can also be performed from images that exhibit speckles, using speckle tracking algorithms.…”

Fluid Dynamics of Heart Development

“…This idea began with Chapman [13] nearly a hundred years ago who surgically removed the heart of chicken embryos and documented the resultant malformation of the circulatory system. Recent advances in quantitative flow visualization techniques at spatial scales on the order of several micrometers have made in vivo exploration of the fluid dynamics of the vertebrate embryonic heart possible [42,43,106]. Hove et al [44] experimentally showed that shear stress imparted on the cardiac walls by the blood flow is important to proper morphological development of the zebrafish heart (Danio rerio).…”

Biomechanics of early cardiac development

“…For example, particle image velocimetry has been used to measure blood flow velocity in the developing hearts of zebrafish (Hove, 2006), mice (Jones et al, 2004) and chicks (Vennemann et al, 2006; Hierck et al, 2008). In this technique, using a high-speed imaging camera, flow markers are followed in time, and blood flow velocities are calculated from the motion of the markers, which is extremely challenging for the rapidly beating developing heart, and resulted in imprecise velocity gradients, and thus wall shear stresses (Hove, 2006). Other groups have used Doppler ultrasound or laser Doppler velocimetry (Butcher et al, 2007; Lucitti et al, 2005; Yoshigi and Keller, 1997; Phoon and Turnbull, 2003; Rugonyi et al, 2008; Ma et al, 2010).…”