Inflammation: 77 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
Tocilizumab improves oxidative stress and endothelial glycocalyx: A mechanism that may explain the effects of biological treatment on COVID-19
Eighty patients with rheumatoid arthritis were randomized to 3 months of the IL-6 receptor blocker tocilizumab or to intensified conventional DMARDs plus glucocorticoids, with 40 age- and sex-matched healthy subjects as a comparison group. Endothelial glycocalyx thickness (sublingual perfused boundary region, PBR), arterial stiffness, echocardiographic myocardial work/strain, and inflammatory and oxidative stress markers were measured before and after treatment. Tocilizumab was associated with reduced PBR (indicating thicker glycocalyx), lower arterial stiffness, greater falls in CRP and oxidative stress markers, and greater improvement in myocardial deformation and work than conventional treatment.
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Published paper
Decreased endothelial glycocalyx thickness is an early predictor of mortality in sepsis
Researchers measured sublingual glycocalyx thickness (as the perfused boundary region, PBR) with sidestream dark-field imaging and GlycoCheck software within 24 hours of ICU admission in 21 septic patients, and compared results with plasma markers and survival. Patients who did not survive to hospital discharge had a thinner glycocalyx (higher PBR) than survivors, and admission PBR discriminated survivors from non-survivors moderately well. PBR correlated with angiopoietin-2 but not with syndecan-1 or severity scores.
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Published paper
Microvascular Alterations During Cardiac Surgery Using a Heparin or Phosphorylcholine-Coated Circuit
In this single-center randomized, blinded trial, 26 adults having on-pump CABG surgery received either a heparin-coated or a phosphorylcholine-coated cardiopulmonary bypass circuit. Sublingual sidestream dark-field imaging (GlycoCheck) and plasma shedding markers showed glycocalyx thinning and shedding in the phosphorylcholine group but not the heparin-coated group, while the fall in perfused vessel density during bypass was similar in both groups.
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Published paper
In Vivo Imaging of the Buccal Mucosa Shows Loss of the Endothelial Glycocalyx and Perivascular Hemorrhages in Pediatric Plasmodium falciparum Malaria
Researchers used incident dark-field video microscopy of the inner cheek (buccal mucosa) in Tanzanian children to measure the perfused boundary region (PBR), an inverse indicator of endothelial glycocalyx thickness, alongside plasma glycocalyx shedding markers. Children with severe malaria had a significantly increased PBR and higher circulating hyaluronic acid, heparan sulfate, sulfated glycosaminoglycans, syndecan-1 and glypican-1 than healthy controls, consistent with substantial glycocalyx loss. Imaging also revealed perivascular hemorrhages and sequestering late-stage parasites, and markers of vascular instability (low angiopoietin-1, high angiopoietin-2) tracked with these changes.
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Published paper
Tie2 Activation Promotes Protection and Reconstitution of the Endothelial Glycocalyx in Human Sepsis
Researchers measured the perfused boundary region (PBR), an inverse marker of endothelial glycocalyx thickness, in sublingual microvessels of septic patients and nonseptic controls, and found thicker PBR (thinner glycocalyx) in sepsis that correlated with serum angiopoietin-2 levels. Serum from septic patients thinned the glycocalyx of cultured human endothelial cells, an effect abolished by blocking angiopoietin-2 or activating the Tie2 receptor. Mechanistically, damage required heparan sulfate loss via heparanase, which Tie2 activation suppressed; Tie2 activation after injury also accelerated glycocalyx recovery.
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Published paper
Association of sublingual microcirculation parameters and endothelial glycocalyx dimensions in resuscitated sepsis
In 30 ICU patients with resuscitated sepsis and 10 healthy controls, researchers simultaneously measured endothelial glycocalyx dimensions (sublingual perfused boundary region, PBR, via GlycoCheck) and conventional sublingual microcirculation parameters (incident dark field imaging). Septic patients had both thicker PBR (indicating glycocalyx damage) and impaired microvascular perfusion, and both correlated with markers of illness severity, but the two sets of measures did not correlate with each other. PBR values agreed well with circulating syndecan-1 and with glycocalyx thickness measured by atomic force microscopy in endothelial cells exposed to patient serum.
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Published paper
Impaired Arterial Elastic Properties and Endothelial Glycocalyx in Patients with Embolic Stroke of Undetermined Source
This case-control study compared 90 patients who had an embolic stroke of undetermined source with 90 controls carrying similar cardiovascular risk factors. ESUS patients had thinner endothelial glycocalyx (higher sublingual perfused boundary region), stiffer arteries (higher pulse wave velocity), more oxidative stress, and impaired left atrial function. Glycocalyx damage correlated with arterial stiffness, which in turn related to left atrial reservoir strain.
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Published paper
Effects of Different Antidiabetic Medications on Endothelial Glycocalyx, Myocardial Function, and Vascular Function in Type 2 Diabetic Patients: One Year Follow-Up Study
One hundred people with poorly controlled type 2 diabetes were assessed before and 12 months after intensifying their antidiabetic treatment, with measurements of arterial stiffness, brachial artery flow-mediated dilation, sublingual endothelial glycocalyx (perfused boundary region by GlycoCheck), heart muscle deformation on echocardiography, and blood markers of oxidative stress. Average HbA1c fell from 8.9% to 7.1%, and this was accompanied by lower arterial stiffness, a smaller perfused boundary region (suggesting a thicker/less penetrable glycocalyx), better endothelial and left ventricular function, and lower oxidative stress markers. In multivariable analysis, incretin-based drugs (GLP-1 receptor agonists and DPP-4 inhibitors) were associated with these improvements over and above the fall in HbA1c.
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Published paper
Effects of high-intensity interval training on microvascular glycocalyx and associated microRNAs
Fifty healthy young adults completed a 4-week high-intensity interval training (HIIT) program consisting of 4 x 30-s all-out runs, with sublingual microvascular imaging (sidestream dark-field, perfused boundary region) before and after. Exercise capacity correlated with glycocalyx measures, and several circulating microRNAs were upregulated by HIIT, with baseline miR-143 predicting later glycocalyx changes. The authors conclude HIIT alters the endothelial glycocalyx of the microvasculature and that miRNAs may serve as markers of early vascular adaptation.
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Published paper
Increase in perfused boundary region of endothelial glycocalyx is associated with higher prevalence of ischemic heart disease and lesions of microcirculation and vascular wall.
This cross-sectional study measured the perfused boundary region (PBR), an index of red blood cell penetration into the endothelial glycocalyx, using sidestream dark-field capillaroscopy in 208 middle-aged patients. Higher PBR values (above about 2 micrometers) were associated with a greater prevalence of ischemic heart disease and cerebral atherosclerosis, as well as structural and functional abnormalities of the arterial wall and skin microcirculation. The authors propose PBR as a reproducible, non-invasive candidate marker of cardiovascular disease.
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Published paper
Derangement of the endothelial glycocalyx in sepsis
This narrative review describes the structure and functions of the endothelial glycocalyx and how it is degraded during sepsis. It covers glycocalyx roles in leukocyte adhesion, anticoagulation, vascular permeability and mechanosensing, methods of assessment (circulating syndecan-1, heparan sulfate, hyaluronan; electron and intravital microscopy; sidestream dark-field imaging with automated PBR analysis), and candidate protective strategies. The authors conclude that no treatment has yet been proven clinically effective and that links between glycocalyx damage, sepsis severity and DIC remain inadequately defined.
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Published paper
Induced Trf2 deletion leads to aging vascular phenotype in mice associated with arterial telomere uncapping, senescence signaling, and oxidative stress
Researchers deleted the telomere-protecting protein Trf2 in adult mice to force telomere 'uncapping' without shortening telomeres, then measured artery and microvessel function. Trf2 deletion produced senescence signaling, oxidative stress, impaired nitric-oxide-dependent vasodilation, thinner endothelial glycocalyx, reduced microvascular perfusion, and modestly higher systolic blood pressure — a pattern resembling normal vascular aging.
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Published paper
Alterations of conjunctival glycocalyx and microcirculation in non-septic critically ill patients
This single-center prospective observational study used sidestream dark-field imaging to assess glycocalyx thickness (perfused boundary region, PBR) and microcirculatory perfusion in the sublingual mucosa and, for the first time, the ocular conjunctiva of non-septic ICU patients. Both cardiac surgical and neurocritical patients showed increased PBR (indicating glycocalyx thinning/damage) at both sites and higher blood syndecan-1 than healthy controls. Correlations between systemic glycocalyx shedding markers and local conjunctival glycocalyx measures were weak or absent.
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Published paper
Effect of acute hypernatremia induced by hypertonic saline administration on endothelial glycocalyx in rabbits.
In 20 rabbits, acute hypernatremia was induced with intravenous 10% NaCl and the sublingual and brain microcirculation were imaged with sidestream dark-field video microscopy before and 20 minutes after infusion. The perfused boundary region (PBR), an index of red blood cell penetration into the endothelial glycocalyx, increased slightly in the sublingual area, while blood syndecan-1 did not change. The authors interpret this as compression or charge alteration of the glycocalyx from transient hypervolemia rather than true shedding.
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Published paper
The Effect of Fluid Loading and Hypertonic Saline Solution on Cortical Cerebral Microcirculation and Glycocalyx Integrity.
In a rabbit craniotomy model, researchers compared one hour of liberal (30 mL/kg/h) versus restrictive (<2 mL/kg/h) balanced isotonic fluid administration, followed by a bolus of either 3.2% hypertonic saline or 0.9% saline. Cortical cerebral microcirculation was imaged with sidestream dark-field video microscopy, and glycocalyx integrity was assessed by the perfused boundary region (PBR) and serum syndecan-1. Liberal fluid loading was associated with poorer cortical vessel perfusion and signs of greater glycocalyx shedding, while hypertonic saline had no measurable effect on these parameters.
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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
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
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
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
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
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
Effects of ultrapure hemodialysis and low molecular weight heparin on the endothelial surface layer
In 20 hemodialysis patients, researchers measured the endothelial surface layer during dialysis sessions using sidestream dark-field imaging (perfused boundary region, PBR) and plasma markers of glycocalyx shedding, varying whether low molecular weight heparin was given at the start of dialysis or 120 minutes in. Plasma syndecan-1 rose significantly during hemodialysis, with the increase appearing to follow heparin administration, while PBR did not change measurably.
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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
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
Acute ischemic injury to the renal microvasculature in human kidney transplantation
During transplant surgery, researchers used sidestream darkfield imaging to observe peritubular capillaries in kidneys from donors after cardiac death (DCD, substantial ischemia) and from living donors (minimal ischemia). DCD kidneys showed markedly poorer microvascular perfusion and biochemical and imaging signs of endothelial glycocalyx degradation, despite similar overall renovascular resistance. The authors conclude that ischemia-reperfusion in kidney grafts involves impaired capillary flow and loss of glycocalyx integrity.
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