Measurement & method: 15 papers
Peer-reviewed work on the endothelial glycocalyx, microvascular health and the ingredients in our formulas, newest first. Abstracts are indexed here and every paper links to the journal.
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Published paper
Erythrocyte Glycocalyx Reports Glomerular Endothelial Glycocalyx Damage in Disease and Predicts Glomerular Albumin Permeability
This paper, published in the Journal of the American Society of Nephrology, reports that the glycocalyx layer on red blood cells reflects damage to the glycocalyx of glomerular endothelial cells in the kidney. The authors propose the erythrocyte glycocalyx as an accessible marker that also predicts glomerular permeability to albumin. Only the title and citation were available, so the methods, population, and numerical results cannot be verified here.
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Published paper
Variability of microcirculatory measurements in healthy volunteers
Two experienced operators each performed three consecutive sublingual GlycoCheck (sidestream dark-field) microcirculation measurements in 49 healthy volunteers to test reproducibility. Single measurements of perfused boundary region (PBR), red blood cell filling percentage, and microvascular vessel density had poor intraobserver reliability, but averaging three measurements raised reliability to acceptable levels. Agreement between the two observers was only fair for PBR and RBC filling and poor for vessel density, though no systematic bias was found.
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Published paper
Identification of novel sublingual parameters to analyze and diagnose microvascular dysfunction in sepsis: the NOSTRADAMUS study (link to Critical Care)
This single-center observational study used sublingual sidestream dark-field videomicroscopy with a new GlycoCheck software version to analyze microvessels in 1-micrometer diameter classes (4-25 um) in 34 septic ICU patients and 17 healthy controls. Sepsis was associated with loss of the very smallest capillaries, impaired capillary recruitment, and increased perfused boundary region (indicating a thinner/more permeable glycocalyx). The authors combined capillary blood volume and PBR into a composite 'Microvascular Health Score' that separated patients from controls and correlated with sepsis severity.
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Published paper
Assessment of the sublingual microcirculation with the GlycoCheck system: Reproducibility and examination conditions
This randomized, controlled methodological study tested how reproducible sublingual glycocalyx measurements with the GlycoCheck system (perfused boundary region, PBR, and red blood cell filling) are, and how they are affected by smoking, a high-calorie meal, and coffee. Reproducibility of single measurements was poor to moderate but improved substantially when 3-5 measurements were averaged, with no meaningful differences between investigators. All three acute exposures worsened PBR and RBC filling, with effects still detectable at 180 minutes.
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Published paper
Evaluation of jejunal microvasculature of healthy anesthetized dogs with sidestream dark field video microscopy
This veterinary study tested whether sidestream dark field (SDF) video microscopy could image and quantify the small blood vessels of the jejunum (small intestine) in 30 healthy anesthetized dogs during spay surgery. Imaging was feasible and produced reference values for microvascular density, red blood cell filling, vessel width, and the perfused boundary region (PBR), an indirect index of glycocalyx thickness. The authors conclude the technique warrants further study, including in dogs with intestinal disease.
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Published paper
Variability of Microcirculatory Measurements in Critically Ill Patients
This study tested how reproducible sublingual GlycoCheck microcirculation measurements are in 60 critically ill patients, using repeated measurements by one or two experienced observers. Single measurements of glycocalyx thickness (perfused boundary region) showed poor reliability, while red blood cell filling percentage and vessel density were more consistent. Averaging three consecutive measurements substantially improved reproducibility for all parameters.
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Published paper
In vivo assessment of the human cerebral microcirculation and its glycocalyx: A technical report
This technical report describes the first in vivo measurement of the human cerebral microcirculation and its endothelial glycocalyx using sidestream dark-field (SDF) imaging with GlycoCheck software during brain surgery. Measurements were taken sublingually (as a reference), and from cortical and hippocampal surfaces in five epilepsy surgery patients, with a sterile slipcover over the camera required in the operating field. Vessel density and perfused boundary region (PBR) showed broadly similar patterns across the three sites, but the sterile slipcover itself altered the measured values.
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Published paper
Bedside analysis of the sublingual microvascular glycocalyx in the emergency room and intensive care unit – the GlycoNurse study
This single-center observational study tested whether bedside sublingual glycocalyx measurement with sidestream dark-field imaging and GlycoCheck software is practical and reproducible in routine emergency and critical care settings. A physician's repeated measurements and measurements by eight trained nurses agreed closely, and the procedure was quick and well tolerated. Perfused boundary region (PBR) values were higher in ICU than ER patients and modestly correlated with markers of acute illness.
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Published paper
Glycocalyx in vivo measurement
This review describes how the endothelial glycocalyx can be assessed in living patients. It contrasts laboratory measurement of circulating shedding products (syndecan-1, heparan sulfate, hyaluronan) with bedside video microscopy techniques such as sidestream dark-field imaging, which estimates glycocalyx dimensions in the sublingual microcirculation via the Perfused Boundary Region.
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Published paper
The Measurement of the Endothelial Glycocalyx as a New Biomarker of Endothelial Derangement in Systemic Sclerosis: A Challenge for the Future
This editorial discusses a companion study by Machin et al. that used automated sublingual microvascular imaging to assess endothelial glycocalyx and perfusion in systemic sclerosis (SSc). The authors argue that glycocalyx-related measures such as the perfused boundary region may detect functional microvascular derangement earlier than structural methods like nailfold videocapillaroscopy. They propose the glycocalyx as a candidate biomarker of endothelial disease activity in early SSc, while noting further validation is required.
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Published paper
Automated Measurement of Microvascular Function Reveals Dysfunction in Systemic Sclerosis: A Cross-sectional Study.
Researchers used automated sidestream dark-field videomicroscopy (GlycoCheck) of sublingual microvessels to compare 40 patients with systemic sclerosis to 10 age-matched healthy controls. Patients with systemic sclerosis had fewer perfused microvessels, lower red blood cell fraction, a larger perfused boundary region (indicating deeper red-cell penetration into the glycocalyx), and thinner glycocalyx measured by a separate manual leukocyte-passage method. The study is descriptive and shows that this automated method can distinguish patients from controls.
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Published paper
Non-invasive assessment of microvascular dysfunction in patients with microvascular angina
This prospective study compared sublingual glycocalyx barrier properties (perfused boundary region, PBR) in 13 patients with microvascular angina (MVA), 13 volunteers, and 14 patients with obstructive coronary artery disease, and additionally measured myocardial perfusion reserve by adenosine stress cardiac MRI in the MVA patients. MVA patients had a larger baseline PBR than volunteers and lacked the normal PBR increase after nitroglycerin, suggesting reduced glycocalyx integrity. The PBR response correlated strongly with the MRI-derived transmural myocardial perfusion reserve index.
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Published paper
Protocol for intraoperative assessment of the human cerebrovascular glycocalyx.
This is a published study protocol (no results) for a multicenter prospective case-control study in the Netherlands that plans to image the endothelial glycocalyx intraoperatively in the human brain. Using sidestream dark-field video microscopy with GlycoCheck software, investigators will measure the perfused boundary region (PBR) and perfused diameter in sublingual, cortical, and (in epilepsy patients only) hippocampal microvessels. The hypothesis is that cerebrovascular glycocalyx thickness is reduced in temporal lobe epilepsy compared with controls, potentially linking glycocalyx damage to blood-brain barrier leakage and seizure susceptibility.
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Published paper
Non-invasive assessment of microvascular dysfunction in families with premature coronary artery disease
This brief research letter reports on the use of non-invasive imaging of the sublingual microcirculation to assess microvascular function in relatives of patients with premature coronary artery disease. The authors, who developed the sidestream dark-field perfused boundary region technique, position this approach as a way to detect microvascular/glycocalyx abnormalities in people at inherited risk of early coronary disease. No abstract text was available, so the specific numerical results cannot be reported here.
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Published paper
Methods for evaluating endothelial function: a position statement from the European Society of Cardiology Working Group on Peripheral Circulation
This European Society of Cardiology Working Group position statement reviews the available in-vivo and ex-vivo methods for assessing endothelial function, from invasive coronary angiography with acetylcholine to flow-mediated dilatation, pulse wave analysis, peripheral arterial tonometry, laser Doppler flowmetry, biochemical markers, endothelial microparticles, progenitor cells, and glycocalyx imaging. For each technique it outlines the physiological rationale, methodology, reproducibility, and clinical applications. The authors conclude that no single method is superior and that endothelial function testing may aid risk stratification but needs further validation before routine clinical use.
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