Over the past decade, since it was first observed in vivo, there has been an explosion in interest in the thin (∼500 nm), gel-like endothelial glycocalyx layer (EGL) that coats the luminal surface of blood vessels. In this review, we examine the mechanical and biochemical properties of the EGL and the latest studies on the interactions of this layer with red and white blood cells. This includes its deformation owing to fluid shear stress, its penetration by leukocyte microvilli, and its restorative response after the passage of a white cell in a tightly fitting capillary. We also examine recently discovered functions of the EGL in modulating the oncotic forces that regulate the exchange of water in microvessels and the role of the EGL in transducing fluid shear stress into the intracellular cytoskeleton of endothelial cells, in the initiation of intracellular signaling, and in the inflammatory response.

https://www.annualreviews.org/doi/pdf/10.1146/annurev.bioeng.9.060906.151959

The Structure and Function of the Endothelial Glycocalyx Layer

The endothelial lining of blood vessels presents a large surface area for exchange of materials between blood and tissues, and is critically involved in many other processes such as regulation of blood flow, inflammatory responses and blood coagulation. It has long been known that the luminal surface of the endothelium is lined with a glycocalyx, a layer of membrane-bound macromolecules which has been determined by electron microscopy to be several tens of nanometers thick. However, investigations in vivo have indicated the presence of a much thicker endothelial surface layer (ESL), with an estimated thickness ranging from 0.5 µm to over 1 µm, that restricts the flow of plasma and can exclude red blood cells and some macromolecular solutes. The evidence for the existence of the ESL, hypotheses about its composition and biophysical properties, its relevance to physiological processes, and its possible clinical implications are considered in this review.

The endothelial surface layer.

Major experimental and theoretical studies on microcirculation and hemorheology are reviewed with the focus on mechanics of blood flow and the vascular wall. Flow of the blood formed elements (red blood cells (RBCs), white blood cells or leukocytes (WBCs) and platelets) in individual arterioles, capillaries and venules, and in microvascular networks is discussed. Mechanical and rheological properties of the formed elements and their interactions with the vascular wall are reviewed. Short-term and long-term regulation of the microvasculature is discussed; the modes of regulation include metabolic, myogenic and shear-stress-dependent mechanisms as well as vascular adaptation such as angiogenesis and vascular remodeling.

Microcirculation and hemorheology

A thick endothelial surface coat consisting of the glycocalyx and associated plasma proteins has been hypothesized to reduce functional capillary volume available for flowing plasma macromolecules and blood cells. The purpose of this study was to compare anatomic and functional capillary diameters available for macromolecules, RBCs, and WBCs in hamster cremaster muscle capillaries. Bright-field and fluorescence microscopy provided similar estimates (mean +/- SE) of the anatomic capillary diameter: 5.1 +/- 0.1 microns (bright field, 39 capillaries in 10 animals) and 5.1 +/- 0.2 microns (membrane dye PKH26, 18 capillaries in 2 animals). Estimates of functional diameters were obtained by measuring the width of RBCs and WBCs and the intracapillary distribution of systemically injected fluorescein isothiocyanate (FITC)-dextran 70. WBCs (5.1 +/- 0.2 microns) fully occupied the anatomic capillary cross section. In contrast, the widths of RBCs (3.9 +/- 0.2 microns, 21 capillaries in 8 animals) and FITC-dextran (4.3 +/- 0.2 microns, 21 capillaries in 8 animals) were significantly smaller than the anatomic capillary diameter. Continuous (1- to 5-minute) excitation of fluorochromes in the capillary lumen (light-dye treatment) increased the width of RBCs passing the treated site from 3.6 +/- 0.3 to 4.4 +/- 0.3 microns (6 capillaries in 4 animals) and the width of the FITC-dextran column from 4.1 +/- 0.2 to 4.6 +/- 0.3 microns (10 capillaries in 7 animals). Furthermore, light-dye treatment increased capillary tube hematocrit by 60% in 40-microns-long capillary segments compared with untreated sites in the same capillaries. It is concluded that the wall of skeletal muscle capillaries is decorated with a 0.4- to 0.5-microns-thick endothelial surface coat, which may represent the true active interface between blood and the capillary wall.

Identification of Distinct Luminal Domains for Macromolecules, Erythrocytes, and Leukocytes Within Mammalian Capillaries

https://people.maths.ox.ac.uk/maini/PKM%20publications/161.pdf

A cellular automaton model for tumour growth in inhomogeneous environment

Resistance to blood flow through peripheral vascular beds strongly influences cardiovascular function and transport to tissue. For a given vascular architecture, flow resistance is determined by the rheological behavior of blood flowing through microvessels. A new approach for calculating the contribution of blood rheology to microvascular flow resistance is presented. Morphology (diameter and length), flow velocity, hematocrit, and topological position were determined for all vessel segments (up to 913) of terminal microcirculatory networks in the rat mesentery by intravital microscopy. Flow velocity and hematocrit were also predicted from mathematical flow simulations, in which the assumed dependence of flow resistance on diameter, hematocrit, and shear rate was optimized to minimize the deviation between measured and predicted values. For microvessels with diameters below approximately 40 microns, the resulting flow resistances are markedly higher and show a stronger dependence on hematocrit than previously estimated from measurements of blood flow in narrow glass tubes. For example, flow resistance in 10-microns microvessels at normal hematocrit is found to exceed that of a corresponding glass tube by a factor of approximately 4. In separate experiments, flow resistance of microvascular networks was estimated from direct measurements of total pressure drop and volume flow, at systemic hematocrits intentionally varied from 0.08 to 0.68. The results agree closely with predictions based on the above-optimized resistance but not with predictions based on glass-tube data. The unexpectedly high flow resistance in small microvessels may be related to interactions between blood components and the inner vessel surface that do not occur in smooth-walled tubes.

T Gessner

Papers

Resistance to blood flow in microvessels in vivo.