Visual and Biochemical Evidence of Glycocalyx Disruption in Human Dengue Infection, and Association With Plasma Leakage Severity

Lam, Phung Khanh; McBride, Angela; Le, Duyen Huynh Thi; Huynh, Trieu Trung; Vink, Hans; Wills, Bridget; Yacoub, Sophie

doi:10.3389/fmed.2020.545813

Cited by 21 publications

(27 citation statements)

References 30 publications

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“…As yet details of the process by which this occurs remain obscure, in part due to difficulties in visualizing the structure of the EGL in vivo, but increased levels of several glycocalyx constituents have been documented, with some evidence indicating associations with the timing and severity of leakage (38)(39)(40), suggesting that structural characteristics of the EGL are altered during human DENV infections. In addition imaging studies of the sublingual microcirculation have shown an increase in the perfused boundary region within microvessels consistent with thinning of the EGL (41). In vitro and mouse model studies have demonstrated that dengue nonstructural protein 1 (NS1) can disrupt the surface glycocalyx both directly and/or through inflammatory-dependent pathways (42,43).…”

Section: Dengue Associated Vascular Leakage In the Context Of The Revmentioning

confidence: 98%

Microvascular Fluid Exchange: Implications of the Revised Starling Model for Resuscitation of Dengue Shock Syndrome

Trieu

Wills

2020

Front. Med.

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Dengue is the most common mosquito-borne viral infection in the world. The most feared complication is a poorly understood vasculopathy that occurs in only a small minority of symptomatic individuals, especially children and young adults, but can result in potentially fatal dengue shock syndrome (DSS). Based mainly on expert opinion, WHO management guidelines for DSS recommend prompt infusion of a crystalloid fluid bolus followed by a tapering crystalloid fluid regimen, supplemented if necessary by boluses of synthetic colloid solutions. However, following publication of a number of major trials undertaken in other, primarily adult, critical care scenarios, use of both synthetic colloid solutions and of fluid boluses for volume expansion have become controversial. Synthetic colloids tend to be used for severe DSS cases in order to boost intravascular oncotic pressure, based on the classic Starling hypothesis in which opposing hydrostatic and oncotic forces determine fluid flow across the microvascular barrier. However, the revised Starling model emphasizes the critical contribution of the endothelial glycocalyx layer (EGL), indicating that it is the effective oncotic pressure gradient across the EGL not endothelial cells per se that opposes filtration. Based on several novel concepts that are integral to the revised Starling model, we review the clinical features of DSS and discuss a number of implications that are relevant for fluid management. We also highlight the need for context-specific clinical trials that address crucially important questions around the management of DSS.

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Section: Dengue Associated Vascular Leakage In the Context Of The Revmentioning

confidence: 98%

Microvascular Fluid Exchange: Implications of the Revised Starling Model for Resuscitation of Dengue Shock Syndrome

Trieu

Wills

2020

Front. Med.

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“…In addition, the software calculates the MVHS using the PBR-hf plus parameters representing the RBC filling and valid vessel density (the subset of vessels with enough red cells for tissue perfusion). Lower values of MVHS is suggested to reflect an overall worse microvascular health [18].…”

Section: Measurements Of Endothelial Glycocalyx Dimensionsmentioning

confidence: 98%

“…Higher PBR indicates thinner glycocalyx [22]. The software also enables assessment of the PBR estimated at a fixed high flow level (PBR-hf), which is suggested to be more accurate than measurements in capillaries without flow [18]. A higher PBR-hf reflects a more degraded glycocalyx.…”

Section: Measurements Of Endothelial Glycocalyx Dimensionsmentioning

confidence: 99%

“…An updated software of the GlycoCheck system enables assessment of the PBR at a fixed high flow level (PBR-hf) and calculation of a MicroVascular Health Score (MVHS). The importance of these new measures has only been sparsely investigated and, to our knowledge, described only in one study focusing on dengue and other febrile illnesses [18]. Thus, the impact of these measures in persons with diabetes is unknown.…”

Section: Introductionmentioning

confidence: 99%

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Endothelial glycocalyx and cardio-renal risk factors in type 1 diabetes

et al. 2021

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Background Glycocalyx lines the inner surface of the capillary endothelium. Capillaroscopy enables visualization of the sublingual capillaries and measurement of the Perfused Boundary Region (PBR) as an estimate of the glycocalyx. Novel software enables assessment of the PBR estimated at a fixed high flow level (PBR-hf) and an overall microvascular assessment by the MicroVascular Health Score (MVHS). Damaged glycocalyx may represent microvascular damage in diabetes and assessment of its dimension might improve early cardio-renal risk stratification. Aim To assess the associations between PBR, PBR-hf and MVHS and cardio-renal risk factors in persons with type 1 diabetes (T1D); and to compare these dimensions in persons with T1D and controls. Methods Cross-sectional study including 161 persons with T1D stratified according to level of albuminuria and 50 healthy controls. The PBR, PBR-hf and MVHS were assessed by the GlycoCheck device (valid measurements were available in 136 (84.5%) with T1D and in all the controls). Higher PBR and PBR-hf indicate smaller glycocalyx width. Lower MVHS represents a worse microvascular health. Results There were no associations between PBR, PBR-hf or MVHS and the cardio-renal risk factors in persons with T1D, except for higher PBR-hf and lower MVHS in females (p = 0.01 for both). There was no difference in PBR, PBR-hf or MVHS in persons with normo-, micro- or macroalbuminuria. The PBR was higher (2.20±0.30 vs. 2.03±0.18μm; p<0.001) and MVHS lower (3.15±1.25 vs. 3.53±0.86μm; p = 0.02) in persons with T1D compared to controls (p≤0.02). After adjustment for cardio-renal risk factors the difference in PBR remained significant (p = 0.001). Conclusions The endothelial glycocalyx dimension was impaired in persons with T1D compared to controls. We found no association between the endothelial glycocalyx dimension and the level of albuminuria or cardio-renal risk factors among persons with T1D. The use of the GlycoCheck device in T1D may not contribute to cardio-renal risk stratification.

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“…One observational study based in Vietnam demonstrated that in patients with Dengue, SDF imaging demonstrated disruption to the glycocalyx, with worse observed glycocalyx injury and higher plasma concentrations of degradation products being associated with worse plasma leakage. The authors reported that in patients with dengue, the perfused boundary region (PBR hf), a surrogate for glycocalyx degradation, was higher in patients with Grade 2 vs. Grade 0 plasma leakage during the critical phase (PBR hf 1.96 vs. 1.36 µm for Grade 2 vs. Grade 0 plasma leakage on days 4-6, respectively, p < 0.001) (38). SDF, unfortunately, also has associated drawbacks including that it is prone to impaired visualization of capillaries, as well as interference of moving blood components, such as erythrocytes, with the quality of the image obtained (39).…”

Section: Studying the Endothelial Glycocalyx: Models And Imaging Techniquesmentioning

confidence: 99%

Studying the Endothelial Glycocalyx in vitro: What Is Missing?

Haymet

Bartnikowski

Wood

et al. 2021

Front. Cardiovasc. Med.

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All human cells are coated by a surface layer of proteoglycans, glycosaminoglycans (GAGs) and plasma proteins, called the glycocalyx. The glycocalyx transmits shear stress to the cytoskeleton of endothelial cells, maintains a selective permeability barrier, and modulates adhesion of blood leukocytes and platelets. Major components of the glycocalyx, including syndecans, heparan sulfate, and hyaluronan, are shed from the endothelial surface layer during conditions including ischaemia and hypoxia, sepsis, atherosclerosis, diabetes, renal disease, and some viral infections. Studying mechanisms of glycocalyx damage in vivo can be challenging due to the complexity of immuno-inflammatory responses which are inextricably involved. Previously, both static as well as perfused in vitro models have studied the glycocalyx, and have reported either imaging data, assessment of barrier function, or interactions of blood components with the endothelial monolayer. To date, no model has simultaneously incorporated all these features at once, however such a model would arguably enhance the study of vasculopathic processes. This review compiles a series of current in vitro models described in the literature that have targeted the glycocalyx layer, their limitations, and potential opportunities for further developments in this field.

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Visual and Biochemical Evidence of Glycocalyx Disruption in Human Dengue Infection, and Association With Plasma Leakage Severity

Cited by 21 publications

References 30 publications

Microvascular Fluid Exchange: Implications of the Revised Starling Model for Resuscitation of Dengue Shock Syndrome

Microvascular Fluid Exchange: Implications of the Revised Starling Model for Resuscitation of Dengue Shock Syndrome

Endothelial glycocalyx and cardio-renal risk factors in type 1 diabetes

Studying the Endothelial Glycocalyx in vitro: What Is Missing?

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