Cardiovascular: 110 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
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
Association of impaired endothelial glycocalyx with arterial stiffness, coronary microcirculatory dysfunction, and abnormal myocardial deformation in untreated hypertensives
This cross-sectional case-control study compared sublingual glycocalyx thickness (measured as perfused boundary region, PBR, by sidestream dark-field imaging/GlycoCheck) in 320 untreated hypertensive patients and 160 normotensive controls. Hypertensives had thicker PBR (indicating thinner, more damaged glycocalyx), stiffer arteries, lower coronary flow reserve, and reduced left ventricular longitudinal strain. Higher PBR remained independently associated with arterial stiffness, coronary microcirculatory dysfunction, and impaired myocardial deformation after adjustment for standard risk factors.
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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
Sublingual functional capillary rarefaction in chronic heart failure
Researchers used sidestream dark-field sublingual videomicroscopy (with perfused boundary region as a glycocalyx measure) to compare capillary density and glycocalyx dimensions in 50 chronic heart failure patients and 35 healthy age-matched controls. Heart failure patients showed substantially fewer functional and perfused capillaries, while glycocalyx thickness differed only marginally. Within the heart failure group, larger PBR (thinner glycocalyx) correlated with inflammatory markers and worse liver/kidney function measures.
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Published paper
Inflammatory and Angiogenic Factors Linked to Longitudinal Microvascular Changes in Hemodialysis Patients Irrespective of Treatment Dose Intensity
This 6-month prospective analysis of the multicenter INTHEMO study compared macro- and microvascular measures in hemodialysis patients receiving more than 12 hours per week of dialysis versus conventional regimens. Dialysis intensity did not predict changes in pulse wave velocity, ambulatory blood pressure, or sublingual glycocalyx measures. Instead, baseline inflammatory and angiogenic biomarkers predicted 6-month change in the perfused boundary region (PBR), a marker of glycocalyx integrity.
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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
Extracellular overhydration linked with endothelial dysfunction in the context of inflammation in haemodialysis dependent chronic kidney disease
This cross-sectional analysis of 72 haemodialysis patients compared fluid status (bioimpedance-derived overhydration) with macrovascular measures (pulse wave velocity, blood pressure), sublingual microvascular glycocalyx measurement (perfused boundary region by GlycoCheck), and a panel of inflammatory/endothelial biomarkers. Overhydrated patients had higher blood pressure and higher VCAM-1, thrombomodulin and IL-6 with lower leptin, while arterial stiffness and glycocalyx PBR did not differ between hydration groups. VCAM-1 was the strongest independent correlate of extracellular fluid excess.
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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
Effects of varenicline and nicotine replacement therapy on arterial elasticity, endothelial glycocalyx and oxidative stress during a 3-month smoking cessation program
In this randomized trial, 188 smokers received either varenicline or nicotine replacement therapy for three months, with vascular and oxidative stress measures taken at baseline, 3 months, and 12 months. Both treatments reduced exhaled carbon monoxide, oxidative stress markers, and arterial stiffness (augmentation index), and improved endothelial glycocalyx integrity measured as sublingual perfusion boundary region. Improvements were somewhat greater with varenicline and were sustained at one year only in those who remained abstinent.
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Published paper
Early detection of left ventricular dysfunction in first-degree relatives of diabetic patients by myocardial deformation imaging: The role of endothelial glycocalyx damage
Researchers compared 40 first-degree relatives of people with type 2 diabetes (normal glucose tolerance), 40 people with abnormal glucose tolerance, and 20 normoglycemic controls without a family history, measuring sublingual glycocalyx thickness (perfused boundary region) and left ventricular deformation by speckle-tracking echocardiography before and 120 minutes after an oral glucose load. Both relatives and dysglycemic subjects had thinner glycocalyx (higher PBR), lower insulin sensitivity, and impaired longitudinal strain and twisting compared with controls. Greater glycocalyx damage tracked with worse myocardial deformation both at baseline and after glucose loading.
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Published paper
Improvement of arterial stiffness and myocardial deformation in patients with poorly controlled diabetes mellitus type 2 after optimization of antidiabetic medication
This study compared arterial stiffness, heart muscle deformation, endothelial function, and sublingual microvascular glycocalyx thickness in 50 patients with poorly controlled type 2 diabetes versus 25 healthy controls, then reassessed the diabetic patients 6 months after their antidiabetic medication was optimized. At baseline, diabetic patients had stiffer arteries, worse left ventricular strain and diastolic indices, and a higher perfusion boundary region (indicating a thinner endothelial glycocalyx). After achieving glycemic control, carotid-femoral pulse wave velocity fell and untwisting velocity and flow-mediated dilatation improved.
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Published paper
P673 Improvement of arterial stiffness and myocardial deformation in patients with poorly controlled diabetes mellitus type 2 after optimization of antidiabetic medication
This conference abstract compared 50 adults with poorly controlled type 2 diabetes with 25 healthy controls using arterial stiffness measures, speckle-tracking echocardiography, sublingual microvascular imaging (GlycoCheck perfused boundary region), and brachial flow-mediated dilation. Diabetic patients had stiffer arteries, worse left ventricular deformation, and a higher PBR (indicating a thinner endothelial glycocalyx). After six months of optimized antidiabetic medication and achieved glycemic control, carotid-femoral pulse wave velocity fell and untwisting velocity and endothelial function improved.
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Published paper
Perturbation of the microvascular glycocalyx and perfusion in infants after cardiopulmonary bypass
Researchers used sidestream dark-field imaging at the ear conch to measure the perfused boundary region (an inverse marker of glycocalyx thickness) and microcirculatory perfusion in 40 infants having congenital heart surgery, compared with children undergoing cardiac catheterization or cleft palate surgery. After surgery with cardiopulmonary bypass, the perfused boundary region increased significantly (indicating glycocalyx thinning) and microvascular perfusion transiently fell, both recovering to baseline by day 7. Control groups showed no significant glycocalyx changes.
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Published paper
Perturbed mechanotransduction by endothelial surface glycocalyx modification greatly impairs the arteriogenic process
In mice, the glycocalyx component hyaluronan was reduced by continuous infusion of the hyaluronan synthase inhibitor 4-methylesculetin before surgical ligation of the femoral artery. Mice with a modified (thinner) endothelial glycocalyx showed markedly impaired recovery of blood flow and failed to enlarge collateral arteries. The authors conclude that an intact glycocalyx is needed for endothelial cells to sense altered shear stress and initiate arteriogenesis.
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Published paper
The impact of periodontal disease treatment on endothelium of sublingual microvessels
Thirty-five patients with severe chronic periodontitis had their sublingual microvessels assessed by sidestream/darkfield microscopy with GlycoCheck RI software before and after treatment. One group received only local anti-inflammatory therapy, the other also underwent periodontal surgery. Glycocalyx measures changed little early on, but six months after surgery the surgical group showed a reduced permeable glycocalyx thickness and increased red blood cell filling of the capillaries.
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Published paper
Side-by-Side Alterations in Glycocalyx Thickness and Perfused Microvascular Density During Acute Microcirculatory Alterations in Cardiac Surgery
This observational study of 36 coronary bypass patients used sublingual sidestream dark-field imaging (GlycoCheck) to track perfused vessel density and perfused boundary region (PBR, an inverse index of glycocalyx thickness) before, during, and after surgery. Onset of cardiopulmonary bypass was accompanied by a fall in perfused vessel density and a rise in PBR, while off-pump surgery showed no such deterioration. Postoperative recovery of both measures occurred with pulsatile but not nonpulsatile bypass flow.
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Published paper
Effect of an acute and chronic slat load on microvascular permeability in healthy subjects.
In a randomized crossover study, 12 healthy men followed 8 days of a low-sodium diet and 8 days of a high-sodium diet, and also received an acute intravenous hypertonic saline load. Microvascular permeability (transcapillary escape rate of radiolabeled albumin) rose after the acute salt infusion but not after chronic dietary salt loading, while sublingual glycocalyx measures (perfused boundary region) and microvascular perfusion were unchanged in all conditions.
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Published paper
Plasma free hemoglobin and microcirculatory response to fresh or old blood transfusions in sepsis
This secondary analysis of a randomized pilot trial compared transfusion of fresh (<10 days) versus old (>15 days) non-leukodepleted red blood cells in 20 septic ICU patients, measuring plasma free hemoglobin, sublingual microcirculation by sidestream dark-field imaging (including perfused boundary region as a glycocalyx index), and near-infrared spectroscopy variables. Plasma free hemoglobin rose after old blood transfusion despite similar free hemoglobin in the blood units themselves, while sublingual microcirculatory parameters, including PBR, did not change significantly in either group. Larger increases in plasma free hemoglobin correlated with decreases in microvascular density and less increase in tissue hemoglobin index.
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Published paper
Characteristics and determinants of the sublingual microcirculation in populations of different ethnicity
This population-based study used sidestream/oblique epi-illumination sublingual capillaroscopy with GlycoCheck software to measure capillary density and the perfused boundary region (PBR, an inverse proxy for glycocalyx thickness) in 252 Han Chinese, 220 She Chinese and 254 Flemish adults. Higher cardiovascular risk (age, BMI, cholesterol, Framingham score) was associated with greater functional capillary recruitment, and in perfused capillaries a higher BMI and higher blood pressure were associated with lower PBR (i.e. apparently thicker glycocalyx). Associations were consistent across the three ethnic groups, although absolute PBR and capillary density differed between Chinese and Flemish participants.
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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
Sublingual microvascular glycocalyx dimensions in lacunar stroke patients
Researchers used sidestream dark-field imaging of the sublingual microcirculation to estimate glycocalyx thickness (via the perfused boundary region, PBR) in 31 patients with lacunar stroke and 19 healthy controls. Overall, PBR did not differ between stroke patients and controls, but the subgroup of stroke patients who also had white matter lesions on MRI showed a significantly larger PBR, suggesting a thinner or more permeable glycocalyx. The authors interpret this as evidence of impaired endothelial barrier function in more extensive cerebral small vessel disease.
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Published paper
Association of kidney function with changes in the endothelial surface layer
This cross-sectional study used sublingual sidestream dark-field imaging (GlycoCheck) to measure the perfused boundary region (PBR), an inverse index of endothelial glycocalyx integrity, in men with end-stage renal disease, kidney transplant recipients, and healthy controls. Patients with ESRD and transplant recipients who developed interstitial fibrosis/tubular atrophy had larger PBR (worse glycocalyx) and higher circulating shed glycocalyx markers, whereas recipients with stable graft function were indistinguishable from controls. Reduced eGFR correlated with a larger PBR and higher endothelial activation markers.
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Published paper
Deeper penetration of erythrocytes into the endothelial glycocalyx is associated with impaired microvascular perfusion
In a population-based sample of 915 middle-aged Dutch adults, researchers used sidestream dark-field imaging with automated GlycoCheck software to measure the perfused boundary region (PBR, a marker of how deeply red blood cells penetrate the endothelial glycocalyx) in sublingual microvessels. Deeper red-cell penetration (higher PBR) was strongly associated with poorer microvascular perfusion, measured as the percentage of time vessel segments contained red blood cells. The authors interpret a low PBR (thicker glycocalyx) as reflecting more efficient microvascular perfusion.
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Published paper
Skeletal muscle capillary density and microvascular function are compromised with aging and type 2 diabetes
This cross-sectional comparison measured muscle capillary density (from biopsies), whole-body insulin sensitivity, and sublingual microvascular measures in 15 young men, 15 older men, and 15 older men with type 2 diabetes. Both aging and type 2 diabetes were associated with fewer capillary contacts per muscle fiber and lower insulin sensitivity. Men with type 2 diabetes also showed a thicker erythrocyte-perfused boundary region on sidestream dark-field imaging, consistent with impaired endothelial glycocalyx function.
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Published paper
Microcirculatory effects of the transfusion of leukodepleted or non-leukodepleted red blood cells in patients with sepsis: a pilot study
This small randomized pilot trial compared sublingual microcirculatory and tissue oxygenation responses one hour after transfusion of leukodepleted versus non-leukodepleted red blood cells in 20 septic ICU patients. Most between-group differences were not significant, though microvascular flow index and blood flow velocity changed more favorably with leukodepleted units. Glycocalyx was assessed by sidestream dark-field perfused boundary region (GlycoCheck software) and by serum syndecan-1, hyaluronan, and heparan sulfate.
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Published paper
Damage of the endothelial glycocalyx in dialysis patients
This cross-sectional case-control study compared the sublingual microvascular glycocalyx in 40 dialysis patients (23 hemodialysis, 17 peritoneal dialysis) with 21 age- and sex-matched healthy controls using sidestream dark-field (SDF) imaging, plus blood markers of glycocalyx shedding. Dialysis patients showed a larger perfused boundary region (PBR) and perfused diameter, indicating red cells penetrating closer to the vessel wall, along with higher serum hyaluronan, syndecan-1, hyaluronidase activity, and sE-selectin. Higher inflammation (CRP >10 mg/L) and a history of cardiovascular disease were associated with greater PBR.
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Published paper
Alteration of the sublingual microvascular glycocalyx in critically ill patients
Using sidestream dark-field video microscopy of the sublingual microcirculation, researchers compared the Perfused Boundary Region (PBR), an index of glycocalyx damage, between 50 critically ill patients and 16 healthy volunteers. PBR was significantly higher in ICU patients, and tended to be highest in those with sepsis, indicating greater glycocalyx disruption. Higher PBR also correlated with more rolling leukocytes in post-capillary venules in a subgroup of septic patients.
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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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Published paper
Effect of sulodexide on endothelial glycocalyx and vascular permeability in patients with type 2 diabetes mellitus
This small open-label study compared endothelial glycocalyx thickness in the sublingual and retinal microcirculation of 10 men with type 2 diabetes and 10 healthy age-matched men, then measured both groups again after 8 weeks of oral sulodexide (200 mg/day), a glycosaminoglycan mixture of heparan and dermatan sulfate. Men with diabetes had thinner glycocalyx in both vascular beds, higher albumin leakage from capillaries, and higher markers of hyaluronan breakdown. After sulodexide, glycocalyx dimensions increased in the diabetes group, with a non-significant trend toward normalized albumin leakage.
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