scholarly journals Links between Endothelial Glycocalyx Changes and Microcirculatory Parameters in Septic Patients

Life ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 790
Author(s):  
Egle Belousoviene ◽  
Inga Kiudulaite ◽  
Vidas Pilvinis ◽  
Andrius Pranskunas
Keyword(s):  
Blood Vessels ◽  
Prospective Observational Study ◽  
Microvascular Dysfunction ◽  
Dark Field ◽  
Endothelial Glycocalyx ◽  
Sidestream Dark Field ◽  
Sublingual Microcirculation ◽  
Endothelial Surface ◽  
Significant Damage ◽  
Video Microscope

The glycocalyx is an endothelial surface layer that is essential for maintaining microvascular homeostasis. Impaired integrity of the endothelial glycocalyx may be directly related to the development of microvascular dysfunction. To explore this hypothesis, we conducted a prospective observational study on adult patients diagnosed with sepsis. The study aimed to evaluate the degree of damage to the glycocalyx and to identify correlations between microcirculatory parameters and glycocalyx thickness based on capillary diameter. Sublingual microcirculation was examined using a handheld Cytocam-incident dark field video microscope. A sidestream dark field video microscope attached to a GlycoCheck monitor was used to determine the perfused boundary regions (PBRs) of sublingual blood vessels grouped by diameter (5–9 μm, 10–19 μm, and 20–25 μm). We identified significant damage to the glycocalyx in sublingual blood vessels of all the aforementioned diameters in septic patients compared to healthy age-matched controls. Furthermore, we found that the PBRs of the smallest capillaries (diameter class 5–9µm) correlated moderately and inversely with both total and perfused blood vessel densities. Collectively, our data suggest that there may be a functional relationship between damage to the endothelial glycocalyx of the smallest capillaries and alterations in the microcirculation observed in response to sepsis.

Abstract MP61: Evidence of Impaired Microvascular Function a Decade After Delivery in Women With Placental Malperfusion Lesions

Circulation ◽  
2020 ◽  
Vol 141 (Suppl_1) ◽  
Author(s):  
Alisse Hauspurg ◽  
Judith Brands ◽  
Robin Gandley ◽  
Matthew F Muldoon ◽  
William Tony Parks ◽  
...  
Keyword(s):  
Disease Risk ◽  
Gestational Hypertension ◽  
Boundary Region ◽  
Dark Field ◽  
Endothelial Glycocalyx ◽  
Sidestream Dark Field ◽  
Sublingual Microcirculation ◽  
Dark Field Imaging ◽  
Median Diameter ◽  
History Of

Introduction: Maternal vascular malperfusion (MVM) lesions in the placenta are characterized by incomplete vascular remodeling and vessel features similar to atherosclerosis. MVM lesions indicate a maladaptive maternal vascular response to pregnancy, are often detected in hypertensive disorders of pregnancy (HDP), and may provide a pathologic link to future cardiovascular disease. The endothelial glycocalyx is a glycoprotein-rich layer that is critical for microvascular health and damage may have an important role in the pathophysiology of microcardiovascular disease risk. Hypothesis: We hypothesized that women with malperfusion lesions of the placenta are more likely to evidence microvascular glycocalyx derangement a decade after delivery compared to women without these lesions and that this effect would be most pronounced among women with a history of HDP. Methods: A total of 412 women with placental pathology (N=129 with MVM lesions, N=283 without MVM lesions) were evaluated at 8-10 years postpartum. Placental specimens were reviewed by a blinded perinatal pathologist . HDP (including preeclampsia and gestational hypertension) were abstracted from the medical record. Glycocalyx barrier function was assessed using sublingual sidestream dark field imaging, with reduction defined as deeper penetration of red blood cells (RBCs) into the glycocalyx of the sublingual microcirculation (5-25μm diameter). We compared the median diameter (size) of microvessels, penetration of RBCs into the glycocalyx (perfused boundary region, PBR) and microvascular density (total length of perfused microvessels/mm 2 surface area) in women with and without MVM lesions. Results: Women with placental MVM lesions had smaller-sized sublingual vessels (median 8.59 μM [IQR 8.12, 9.19] vs. 9.01 μM [IQR 8.37, 9.64]; p<0.001), and a lower density of vessels compared to women without lesions. Glycocalyx perfused boundary region was unexpectedly lower in women with MVM lesions (median 2.20 μM [IQR 2.06, 2.43] vs. 2.32 μM [IQR 2.15, 2.50]; p=0.003) in 10-19 μM vessels. Women with HDP and MVM lesions appear to be the most impacted, with the smallest size vessels (median 8.47 [IQR 8.09-9.13]) and the lowest glycocalyx PBR across all vessel sizes. Women with MVM lesions without a HDP similarly had evidence of microvascular glycocalyx derangement whereas women with HDP without placental lesions had a glycocalyx profile similar to women without MVM or a history of HDP. Conclusions: A decade after delivery, women with a history of placental malperfusion lesions had alterations in microvascular perfusion. Women with MVM lesions and a history of HDP appear to be the most severely impacted, which may reflect an underlying maladaptive vascular phenotype detected in the placenta at the time of pregnancy that might provide pathologic insight into future maternal microvascular health.

scholarly journals Effects of a single aerobic exercise on perfused boundary region and microvascular perfusion: a field study

2021 ◽  
Author(s):  
Alexander Fuchs ◽  
Tobias Neumann ◽  
Hendrik Drinhaus ◽  
Anika Herrmann ◽  
Hans Vink ◽  
...  
Keyword(s):  
Surface Layer ◽  
Aerobic Exercise ◽  
Linear Regression Analysis ◽  
Boundary Region ◽  
Dark Field ◽  
Microvascular Perfusion ◽  
Sidestream Dark Field ◽  
Endothelial Surface Layer ◽  
Sublingual Microcirculation ◽  
Endothelial Surface

AbstractThe endothelium and the glycocalyx play a pivotal role in regulating microvascular function and perfusion in health and critical illness. It is unknown today, whether aerobic exercise immediately affects dimensions of the endothelial surface layer (ESL) in relation to microvascular perfusion as a physiologic adaption to increased nutritional demands. This monocentric observational study was designed to determine real-time ESL and perfusion measurements of the sublingual microcirculation using sidestream dark field imaging performed in 14 healthy subjects before and after completing a 10 km trial running distance. A novel image acquisition and analysis software automatically analysed the perfused boundary region (PBR), an inverse parameter for red blood cell (RBC) penetration of the ESL, in vessels between 5 and 25 µm diameter. Microvascular perfusion was assessed by calculating RBC filling percentage. There was no significant immediate effect of exercise on PBR and RBC filling percentage. Linear regression analysis revealed a distinct association between change of PBR and change of RBC filling percentage (regression coefficient β: − 0.026; 95% confidence interval − 0.043 to − 0.009; p = 0.006). A single aerobic exercise did not induce a change of PBR or RBC filling percentage. The endothelium of the microvasculature facilitates efficient perfusion in vessels reacting with an increased endothelial surface layer.

scholarly journals Microvascular dysfunction in COVID-19: the MYSTIC study

Angiogenesis ◽  
2020 ◽  
Author(s):  
Alexandros Rovas ◽  
Irina Osiaevi ◽  
Konrad Buscher ◽  
Jan Sackarnd ◽  
Phil-Robin Tepasse ◽  
...  
Keyword(s):  
Microvascular Dysfunction ◽  
Boundary Region ◽  
Dark Field ◽  
Endothelial Glycocalyx ◽  
Vascular Involvement ◽  
Enzyme Linked Immunosorbent Assay ◽  
Blood Levels ◽  
Vascular Density ◽  
Sidestream Dark Field ◽  
Cross Sectional

Abstract Rationale Pre-clinical and autopsy studies have fueled the hypothesis that a dysregulated vascular endothelium might play a central role in the pathogenesis of ARDS and multi-organ failure in COVID-19. Objectives To comprehensively characterize and quantify microvascular alterations in patients with COVID-19. Methods Hospitalized adult patients with moderate-to-severe or critical COVID-19 (n = 23) were enrolled non-consecutively in this prospective, observational, cross-sectional, multi-center study. Fifteen healthy volunteers served as controls. All participants underwent intravital microscopy by sidestream dark field imaging to quantify vascular density, red blood cell velocity (VRBC), and glycocalyx dimensions (perfused boundary region, PBR) in sublingual microvessels. Circulating levels of endothelial and glycocalyx-associated markers were measured by multiplex proximity extension assay and enzyme-linked immunosorbent assay. Measurements and main results COVID-19 patients showed an up to 90% reduction in vascular density, almost exclusively limited to small capillaries (diameter 4–6 µm), and also significant reductions of VRBC. Especially, patients on mechanical ventilation showed severe glycocalyx damage as indicated by higher PBR values (i.e., thinner glycocalyx) and increased blood levels of shed glycocalyx constituents. Several markers of endothelial dysfunction were increased and correlated with disease severity in COVID-19. PBR (AUC 0.75, p = 0.01), ADAMTS13 (von Willebrand factor-cleaving protease; AUC 0.74, p = 0.02), and vascular endothelial growth factor A (VEGF-A; AUC 0.73, p = 0.04) showed the best discriminatory ability to predict 60-day in-hospital mortality. Conclusions Our data clearly show severe alterations of the microcirculation and the endothelial glycocalyx in patients with COVID-19. Future therapeutic approaches should consider the importance of systemic vascular involvement in COVID-19.

scholarly journals Effects of high-intensity interval training on microvascular glycocalyx and associated microRNAs

2019 ◽  
Vol 316 (6) ◽  
pp. H1538-H1551 ◽  
Author(s):  
Boris Schmitz ◽  
Hannah Niehues ◽  
Malte Lenders ◽  
Lothar Thorwesten ◽  
Andreas Klose ◽  
...  
Keyword(s):  
High Intensity ◽  
Interval Training ◽  
Dark Field ◽  
Endothelial Glycocalyx ◽  
High Intensity Interval Training ◽  
Sidestream Dark Field ◽  
Sidestream Dark Field Imaging ◽  
High Intensity Interval ◽  
Glycocalyx Thickness

High-intensity interval training (HIIT) has been proposed to exert vasculoprotective effects. This study aimed to evaluate whether HIIT affects the microvasculature, including the endothelial glycocalyx barrier, and to identify associated microRNAs (miRNAs). Fifty healthy participants (23.1 ± 3.0 yr) performed a 4-wk 4 × 30-s all-out running HIIT. Sidestream dark-field imaging was performed at baseline and follow-up to detect changes of the sublingual microvasculature including the endothelial glycocalyx. Exercise parameters were determined by continuous running field test and documentation of high-intensity runs. miRNAs potentially associated with glycocalyx thickness were selected by structured literature search and blood samples for miRNA, and lactate measurements were drawn at baseline and follow-up HIIT. At baseline, a correlation between maximal exercise performance capacity and glycocalyx thickness (determined by perfused boundary region) was detected ( P = 0.045, r = 0.303). Increased exercise performance at follow-up also correlated with glycocalyx thickness ( P = 0.031, r = 0.416), and increased high-intensity sprinting speed was associated with an increased number of perfused vessels ( P = 0.0129, r = 0.449). Literature search identified miR-143, -96-5p, and -24, which were upregulated by HIIT already at baseline and showed an association with peak blood lactate levels after sprints (all P < 0.05). Moreover, increased baseline miR-143 levels predicted increased glycocalyx thickness at follow-up (AUCmiR-143 = 0.92, 95% confidence interval, 0.81–1.0, P = 0.0008). Elevated resting miR-126 levels after the intervention were associated with cell-free versican mRNA levels. We conclude that HIIT induces changes in the endothelial glycocalyx of the microvasculature. Associated miRNAs such as miR-143 may represent a tool for monitoring early vasculoprotective adaptations to physical activity. NEW & NOTEWORTHY High-intensity interval training is known to improve health-related fitness in general and in lifestyle-induced chronic diseases. To visualize microvasculature structure and to detect exercise-induced changes, sublingual sidestream dark-field imaging microscopy was used, and circulating miRNAs were measured. This study shows that exercise-induced changes correlate with associated circulating miRNA, which might be useful for monitoring vasculoprotective effects. Furthermore, sidestream dark-field imaging may represent a sensitive tool for the early detection of exercise-induced systemic vascular changes.

scholarly journals Decreased endothelial glycocalyx thickness is an early predictor of mortality in sepsis

2020 ◽  
Vol 48 (3) ◽  
pp. 221-228
Author(s):  
Daniëlle MH Beurskens ◽  
Martine E Bol ◽  
Tammo Delhaas ◽  
Marcel CG van de Poll ◽  
Chris PM Reutelingsperger ◽  
...  
Keyword(s):  
Organ Failure ◽  
Early Stage ◽  
Characteristic Curve ◽  
Area Under The Curve ◽  
Dark Field ◽  
Endothelial Glycocalyx ◽  
Pathophysiological Mechanism ◽  
Heparin Binding ◽  
Sidestream Dark Field ◽  
Glycocalyx Thickness

Microcirculatory alterations play an important role in the early phase of sepsis. Shedding of the endothelial glycocalyx is regarded as a central pathophysiological mechanism causing microvascular dysfunction, contributing to multiple organ failure and death in sepsis. The objective of this study was to investigate whether endothelial glycocalyx thickness at an early stage in septic patients relates to clinical outcome. We measured the perfused boundary region (PBR), which is inversely proportional to glycocalyx thickness, of sublingual microvessels (5–25 µm) using sidestream dark field imaging. The PBR in 21 patients with sepsis was measured within 24 h of admission to the intensive care unit (ICU). In addition, we determined plasma markers of microcirculatory dysfunction and studied their correlation with PBR and mortality. Endothelial glycocalyx thickness in sepsis was significantly lower for non-survivors as compared with survivors, indicated by a higher PBR of 1.97 [1.85, 2.19]µm compared with 1.76 [1.59, 1.97] µm, P=0.03. Admission PBR was associated with hospital mortality with an area under the curve of 0.778 based on the receiver operating characteristic curve. Furthermore, PBR correlated positively with angiopoietin-2 (rho=0.532, P=0.03), indicative of impaired barrier function. PBR did not correlate with Acute Physiology and Chronic Health Evaluation IV (APACHE IV), Sequential Organ Failure Assessment score (SOFA score), lactate, syndecan-1, angiopoietin-1 or heparin-binding protein. An increased PBR within the first 24 h after ICU admission is associated with mortality in sepsis. Further research should be aimed at the pathophysiological importance of glycocalyx shedding in the development of multi-organ failure and at therapies attempting to preserve glycocalyx integrity.

New insights into antiphospholipid-related endothelial dysfunction by assessment of vascular glycocalyx layer: results from a preliminary cross-sectional study

Lupus ◽  
2020 ◽  
Vol 29 (2) ◽  
pp. 157-164 ◽  
Author(s):  
S Miranda ◽  
P Billoir ◽  
M Le Besnerais ◽  
R Joannides ◽  
V Richard ◽  
...  
Keyword(s):  
Endothelial Dysfunction ◽  
Plasma Level ◽  
Thiobarbituric Acid ◽  
Intima Media Thickness ◽  
Carotid Intima Media Thickness ◽  
Dark Field ◽  
Endothelial Glycocalyx ◽  
Sidestream Dark Field ◽  
Cross Sectional ◽  
Early Atherosclerosis

Introduction Antiphospholipid syndrome (APS) is associated with greater atherothrombotic risk and endothelial dysfunction, suggesting that endothelial glycocalyx is impaired in this disease. Objectives The aim was to investigate the endothelial glycocalyx and the relationship between glycocalyx markers, endothelial dysfunction parameters and atherosclerotic markers in APS. Methods A total of 15 primary arterial APS patients and healthy controls were included in the study. Glycocalyx was assessed in both groups by sublingual sidestream dark field imaging and syndecan-1 plasma level. Endothelial function was evaluated by brachial artery flow-mediated dilatation (FMD) and early atherosclerosis by carotid intima media thickness (IMT). Thrombotic profile was also performed by measuring the plasma level of the tissue factor (TF). Results APS patients had significantly increased syndecan-1 plasma level 38.6 ± 5.0 pg/ml vs. 19.1 ± 3.5 pg/ml; p < 0.01 and a reduced glycocalyx thickness 0.26 ± 0.03 µm vs. 0.75 ± 0.07 µm; p < 0.01 compared with control. FMD was impaired in APS patients compared with control, 5.68% ± 0.42 vs. 8.29 ± 0.30, p < 0.01, respectively. IMT was significantly increased in APS patients compared with control, 0.52 ± 0.13 mm vs. 0.40 ± 0.06 mm, p < 0.01, respectively. Soluble TF, thiobarbituric acid-reactive substances levels were increased in the sera from APS patients compared with control. Conclusions This preliminary study supports, for the first time, that in APS patients endothelial glycocalyx is impaired, which could lead to thrombosis, endothelial dysfunction and early atherosclerosis.

scholarly journals Exposure to acute normobaric hypoxia results in adaptions of both the macro- and microcirculatory system

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Moritz Mirna ◽  
Nana-Yaw Bimpong-Buta ◽  
Fabian Hoffmann ◽  
Thaer Abusamrah ◽  
Thorben Knost ◽  
...  
Keyword(s):  
Cardiac Output ◽  
Acute Hypoxia ◽  
Capillary Density ◽  
Dark Field ◽  
Normobaric Hypoxia ◽  
Vessel Density ◽  
Resistance Arteries ◽  
Compensatory Mechanisms ◽  
Sidestream Dark Field ◽  
Sublingual Microcirculation

AbstractAlthough acute hypoxia is of utmost pathophysiologic relevance in health and disease, studies on its effects on both the macro- and microcirculation are scarce. Herein, we provide a comprehensive analysis of the effects of acute normobaric hypoxia on human macro- and microcirculation. 20 healthy participants were enrolled in this study. Hypoxia was induced in a normobaric hypoxia chamber by decreasing the partial pressure of oxygen in inhaled air stepwisely (pO2; 21.25 kPa (0 k), 16.42 kPa (2 k), 12.63 kPa (4 k) and 9.64 kPa (6 k)). Macrocirculatory effects were assessed by cardiac output measurements, microcirculatory changes were investigated by sidestream dark-field imaging in the sublingual capillary bed and videocapillaroscopy at the nailfold. Exposure to hypoxia resulted in a decrease of systemic vascular resistance (p < 0.0001) and diastolic blood pressure (p = 0.014). Concomitantly, we observed an increase in heart rate (p < 0.0001) and an increase of cardiac output (p < 0.0001). In the sublingual microcirculation, exposure to hypoxia resulted in an increase of total vessel density, proportion of perfused vessels and perfused vessel density. Furthermore, we observed an increase in peripheral capillary density. Exposure to acute hypoxia results in vasodilatation of resistance arteries, as well as recruitment of microvessels of the central and peripheral microcirculation. The observed macro- and microcirculatory effects are most likely a result from compensatory mechanisms to ensure adequate tissue oxygenation.

Evaluation of a shorter algorithm in an automated analysis of sublingual microcirculation

2020 ◽  
Vol 76 (2) ◽  
pp. 287-297
Author(s):  
Raphael Romano Bruno ◽  
Mara Schemmelmann ◽  
Jakob Wollborn ◽  
Malte Kelm ◽  
Christian Jung
Keyword(s):  
Video Quality ◽  
Quality Measurement ◽  
Automated Analysis ◽  
Measurement Procedure ◽  
Dark Field ◽  
Frame Rate ◽  
Sidestream Dark Field ◽  
Sublingual Microcirculation ◽  
Promising Tool ◽  
Measurement Results

OBJECTIVE: Diagnostic and risk stratification in intensive and emergency medicine must be fast, accurate, and reliable. The assessment of sublingual microcirculation is a promising tool for this purpose. However, its value is limited because the measurement is time-consuming in unstable patients. This proof-of-concept validation study examines the non-inferiority of a reduced frame rate in image acquisition regarding quality, measurement results, and time. METHODS: This prospective observational study included healthy volunteers. Sublingual measurement of microcirculation was performed using a sidestream dark field camera (SDF, MicroVision Medical®). Video-quality was evaluated with a modified MIQS (microcirculation image quality score). AVA 4.3C software calculated microcirculatory parameters. RESULTS: Thirty-one volunteers were included. There was no impact of the frame rate on the time needed by the software algorithm to measure one video (4.5 ± 0.5 minutes) for AVA 4.3C. 86 frames per video provided non inferior video quality (MIQS 1.8 ± 0.7 for 86 frames versus MIQS 2.2 ± 0.6 for 215 frames, p < 0.05), equal results for all microcirculatory parameters, but did not result in an advantage in terms of speed. No complications occurred. CONCLUSION: Video captures with 86 frames offer equal video quality and results for consensus parameters compared to 215 frames. However, there was no advantage regarding the time needed for the overall measurement procedure.

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