The Functions of Endothelial Glycocalyx and Their Effects on Patient Outcomes During the Perioperative Period: A Review of Current Methods to Evaluate Structure-Function Relations in the Glycocalyx in Both Basic Research and Clinical Settings

Curry, Fitz Roy E; Arkill, Kenton P.; Michel, C. C.

doi:10.1007/978-3-030-48374-6_3

Cited by 6 publications

(10 citation statements)

References 113 publications

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“…While the importance of RBCs has been more universally recognized than the ESL, the other major player in this study, there has been an increasing body of evidence regarding the importance of the ESL and its properties including its thickness (Secomb et al, 1998(Secomb et al, , 2001c, adhesivity , structural organization, porosity, and structural rigidity (Curry et al, 2020). One of the earliest pieces of evidence for the ESL's importance was provided by comparisons that showed that the effective viscosity of blood in glass tubes (Pries et al, 1992) was significantly lower than the effective viscosity of blood in vessels (Pries et al, 1990(Pries et al, , 1994 with approximately the same diameter.…”

Section: Introductionmentioning

confidence: 91%

“…Altering ESL properties throughout a network, as may occur during pathological events like inflammation, can lead to altered flow resistances, flow distribution, and distribution of transported materials. Studies have also shown that the ESL has many other important roles such as acting as a molecular sieve for plasma proteins (Levick, 2004), a barrier to adhesive activities (Curry et al, 2020), and a mediator for shear-induced vasodilatory responses (Secomb et al, 2001a,b;Fu and Tarbell, 2013). With increasing evidence of the ESL's importance, the number of related studies have concomitantly grown (Liu et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

“…Only relatively recently have individuals started to recognize that the material that coats the vessel wall can best be represented by two, not one, regions. Curry et al (2020) suggested the existence of both an inner layer about 0.05-0.4 µm thick containing membranebound macromolecules arranged in a quasi-periodic fash-ion, the endothelial glycocalyx, and an outer layer about 1 µm thick (or more (Secomb et al, 2001c;Yen et al, 2012)) containing a more porous gel-like solution that may include nanobubbles of oxygen, nitrogen and carbondioxide (Reines and Ninham, 2019). The outer layer is farthest from the wall and directly interacts with the RBCs while the inner layer, when healthy, typically does not.…”

Section: Introductionmentioning

confidence: 99%

“…For instance, we use the term "osmotic pressure difference" interchangeably with "structural rigidity" because the structural rigidity of that layer has been explained by the presence of an osmotic pressure difference between the lumen and ESL region that causes invading cells to be pushed back by that pressure difference (Secomb et al, 1998). More details on the bilayer nature of the vessel wall coating can be found in Curry et al (2020) and Triebold and Barber (2022).…”

Section: Introductionmentioning

confidence: 99%

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The Effect of the Endothelial Surface Layer on Cell-Cell Interactions in Microvessel Bifurcations.

Triebold,

Barber

2024

Preprint

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Red blood cells (RBCs) carry oxygen and make up 40-45% of blood by volume. Because of their finite size and their large volume fraction, they are heterogeneously distributed throughout the body. This is partially because RBCs are distributed or partitioned nonuniformly at diverging vessel bifurcations where blood flows from one vessel into two. Despite its increased recognition as an important player in the microvasculature, few studies have explored how the endothelial surface layer (ESL; a vessel wall coating) may affect partitioning and RBC dynamics at diverging vessel bifurcations. Here we use a mathematical and computational model to consider how altering ESL properties, as can occur in pathological scenarios, change partitioning, RBC deformation and penetration of the ESL. The two-dimensional finite element model considers pairs of cells, represented by interconnected viscoelastic elements, passing through an ESL lined diverging vessel bifurcation. The properties of the ESL include the hydraulic resistivity and an osmotic pressure difference modeling how easily fluid flows through the ESL and how easily the ESL is structurally compressed, respectively. We find that cell-cell interaction leads to more uniform partitioning and greatly enhances the effects of ESL properties especially for deformation and penetration. This includes the trend that increased hydraulic resistivity leads to more uniform partitioning, increased deformation, and decreased penetration. It also includes the trend that decreased osmotic pressure increases penetration.

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Section: Introductionmentioning

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The Effect of the Endothelial Surface Layer on Cell-Cell Interactions in Microvessel Bifurcations.

Triebold,

Barber

2024

Preprint

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“…The "small pores" are the main pathways for exchange of fluid and small hydrophilic solutes and ions. We identify the glycocalyx together with the intercellular clefts of continuous endothelia that act as hydraulic resistances in series as the small pore system (Levick and Michel, 2010;Curry, 2018;Curry et al, 2020;Michel et al, 2020). The large pore system is the separate parallel route that is taken by macromolecules to enter the ISF.…”

Section: Introductionmentioning

confidence: 99%

The Colloid Osmotic Pressure Across the Glycocalyx: Role of Interstitial Fluid Sub-Compartments in Trans-Vascular Fluid Exchange in Skeletal Muscle

Curry

Michel

2021

Front. Cell Dev. Biol.

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The primary purpose of these investigations is to integrate our growing knowledge about the endothelial glycocalyx as a permeability and osmotic barrier into models of trans-vascular fluid exchange in whole organs. We describe changes in the colloid osmotic pressure (COP) difference for plasma proteins across the glycocalyx after an increase or decrease in capillary pressure. The composition of the fluid under the glycocalyx changes in step with capillary pressure whereas the composition of the interstitial fluid takes many hours to adjust to a change in vascular pressure. We use models where the fluid under the glycocalyx mixes with sub-compartments of the interstitial fluid (ISF) whose volumes are defined from the ultrastructure of the inter-endothelial cleft and the histology of the tissue surrounding the capillaries. The initial protein composition in the sub-compartments is that during steady state filtration in the presence of a large pore pathway in parallel with the “small pore” glycocalyx pathway. Changes in the composition depend on the volume of the sub-compartment and the balance of convective and diffusive transport into and out of each sub-compartment. In skeletal muscle the simplest model assumes that the fluid under the glycocalyx mixes directly with a tissue sub-compartment with a volume less than 20% of the total skeletal muscle interstitial fluid volume. The model places limits on trans-vascular flows during transient filtration and reabsorption over periods of 30–60 min. The key assumption in this model is compromised when the resistance to diffusion between the base of the glycocalyx and the tissue sub-compartment accounts for more than 1% of the total resistance to diffusion across the endothelial barrier. It is well established that, in the steady state, there can be no reabsorption in tissue such as skeletal muscle. Our approach extends this idea to demonstrate that transient changes in vascular pressure favoring initial reabsorption from the interstitial fluid of skeletal muscle result in much less fluid exchange than is commonly assumed. Our approach should enable critical evaluations of the empirical models of trans-vascular fluid exchange being used in the clinic that do not account for the hydrostatic and COPs across the glycocalyx.

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Dependence of red blood cell dynamics in microvessel bifurcations on the endothelial surface layer’s resistance to flow and compression

Triebold

Barber

2022

Biomech Model Mechanobiol

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draulic resistivity and/or decreasing osmotic pressure differences (ESL resistance to compression) produced four behaviors: 1) RBC partitioning nonuniformity increased slightly; 2) RBC deformation decreased; 3) RBC velocity decreased relative to blood flow velocity; and 4) RBCs penetrated more deeply into the ESL. Decreasing the ESL's resistance to flow and/or compression to pathological levels could lead to more frequent cell adhesion and clotting as well as impaired vascular regulation due to weaker ATP and nitric oxide release. Potential mechanisms that can contribute to these behaviors are also discussed.

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The Functions of Endothelial Glycocalyx and Their Effects on Patient Outcomes During the Perioperative Period: A Review of Current Methods to Evaluate Structure-Function Relations in the Glycocalyx in Both Basic Research and Clinical Settings

Cited by 6 publications

References 113 publications

The Effect of the Endothelial Surface Layer on Cell-Cell Interactions in Microvessel Bifurcations.

The Effect of the Endothelial Surface Layer on Cell-Cell Interactions in Microvessel Bifurcations.

The Colloid Osmotic Pressure Across the Glycocalyx: Role of Interstitial Fluid Sub-Compartments in Trans-Vascular Fluid Exchange in Skeletal Muscle

Dependence of red blood cell dynamics in microvessel bifurcations on the endothelial surface layer’s resistance to flow and compression

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