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...