Glycocalyx & vascular Research

Discover the latest research in glycocalyx & vascular system research

The NOSTRADAMUS Study: Microvascular Dysfunction in Sepsis

Alexandros Rovas, Jan Sackarnd, Jan Rossaint, Stefanie Kampmeier, Hermann Pavenstädt, Hans Vink & Philipp Kümpers
Critical Care volume 25, Article number: 112 (2021)

A new study using GlycoCheck, and co-authored by GlycoCheck Chief Science Offer, Dr. Hans Vink, reports new findings of research on patients with sepsis. The study, titled “Identification of novel sublingual parameters to analyze and diagnose microvascular dysfunction in sepsis: the NOSTRADAMUS study” was published in Critical Care. Critical Care is a high-quality, peer-reviewed, international clinical medical journal that provides a comprehensive overview of the intensive care field.

“For the first time, we can now determine quantitative microvascular scores that correlate very well with accepted clinical parameters in individual sepsis patients for a wide range of clinical severities,” said Dr. Vink, Co-Founder of GlycoCheck.

“The new GlycoCheck software system represents a significant upgrade for researchers and healthcare practitioners,” said Robert Long, CEO and Co-Founder of GlycoCheck and Microvascular Health Solutions. “For several years, GlycoCheck has been used globally in groundbreaking research to understand the complex nature of the endothelial glycocalyx.”

The study concludes that new important diameter-specific quantification and differentiated analysis of RBC kinetics is a key to understand microvascular dysfunction in sepsis. MVHSdynamic, which has a broad bandwidth to detect micro-vascular (dys-) function, might serve as a valuable tool to detect microvascular impairment in critically ill patients.

Dietary Glycocalyx Precursor Supplementation Ameliorates Age‐Related Vascular Dysfunction

Daniel R Machin, Daniel Nguyen, R Colton Bramwell, Lisa A Lesniewski, and Anthony J Donator
The FASEB Journal (volume 33, Issue 1_supplement, 01 April 2019):

Abstract

Large elastic artery stiffening and endothelial dysfunction, and associated reductions in nitric oxide (NO) bioavailability, are central features of vascular aging. We have recently demonstrated that the glycocalyx, a gel-like structure that is bound to the luminal surface of the vascular endothelium, is dysfunctional in the aged vasculature. The glycocalyx has several functions that are critical for the maintenance of a healthy vasculature. We sought to determine if chronic dietary supplementation of glycocalyx precursors (glucosamine sulfate, fucoidan, superoxide dismutase, and high molecular weight hyaluronan) could restore glycocalyx function, while concomitantly ameliorating age-related vascular dysfunction. Young (Y: 7 mo) and old (O: 30 mo) male B6D2F1 mice consumed a control (C) or glycocalyx precursor (GP: 37 mg/kg encapsulated chow provided courtesy of MicroVascular Health Solutions, LLC [U.S. Patent Serial No. 9,943,572]) diet ad libitum for 10 weeks. Glycocalyx barrier function (perfused boundary region [PBR]) was evaluated in the mesenteric microcirculation using an intravital microscope equipped with an automated capture and analysis system. PBR was ~13% higher in OC compared to YC, suggestive of an age-related impairment in glycocalyx barrier function, and this was normalized in OGP mice (Both P<0.05; Figure 1). At baseline, aortic pulse wave velocity (PWV), a measure of large artery stiffness, was higher in OC and OGP compared with YC mice (Both P<0.05; Figure 2). However, after the dietary intervention, PWV decreased by ~13% in OGP (P<0.05), whereas, PWV was unchanged in OC and YC mice after the 10 week period (P>0.05). We assessed endothelial function by endothelium-dependent dilation (EDD, maximal response to acetylcholine [ACh]) in the carotid artery. Carotid artery EDD was higher in YC and OGP compared to OC mice (92.5±2.4 and 90.7±2.3 vs. 69.0±4.9%, respectively, P<0.05). EDD of OGP was similar to YC mice (P>0.05). After incubation with the nitric oxide (NO) synthase inhibitor, L-NAME, the dilatory response did not differ between groups (P>0.05). NO bioavailability (max ACh dilation – max ACh+L-NAME dilation) was ~10–14 fold higher in YC and OGP compared to OC mice (Both P<0.05; Figure 3). Endothelium-independent dilation (vasodilation to sodium nitroprusside) was not different between groups (P>0.05). In young mice, GP diet did not affect any of the aforementioned measurements (P>0.05). In conclusion, 10 weeks of dietary GP supplementation in old mice restores glycocalyx barrier function that is accompanied by reduced aortic stiffness and augmented EDD and NO bioavailability, suggesting that the glycocalyx may be an effective therapeutic target for vascular dysfunction in older adults.

Endocalyx: Pilot Study in 13 Healthy Volunteers

Summary of Findings from Clinical Studies

6.3.2 Food supplement

A pilot study was conducted among 13 healthy volunteers receiving the Endocalyx food supplement. After 3 months, the Microvascular Health Index measured by SDF imaging improved by 31%. After 4 months, the Microvascular Health Index in the volunteers improved by 50%. This showed the beneficial effects of the food supplement on the microvasculature as it significantly increased capillary density and red blood cell filling percentage, and reduced the perfused boundary region (unpublished data, H. Vink).

Summary of Known and Potential Risks and Benefits

6.4.2 Food supplement

In the pilot study with Endocalyx, no serious adverse effects were reported. One side effect that was reported was dizziness, as the Endocalyx supplement lowered the systolic blood pressure. The supplement is already used in general practitioners’ offices in the United States and to date; no one reported any major side effects. Studies conducted with the individual ingredients also did not report any serious adverse effects. A possible side effect may be an unknown allergic reaction to one of the ingredients of the supplement. Benefits of the Endocalyx food supplement in diabetic patients remain to be established but are mainly improving microvascular health by supporting endothelial glycocalyx function.

Dietary Interventions on Glycocalyx Dimensions in South Asian Patients With Diabetic Nephropathy. (Glycotreat)

Leiden University Medical Center

Clinical Trial Study

Sponsor:
Leiden University Medical Center

Collaborators:
Dutch Kidney Foundation
Health Holland
Radboud University

Subsidizing Party:
Health Holland (Dutch Top Sector Life Sciences & Health)
Laan van Nieuw Oost-Indië 334,
2593 CE Den Haag
The Netherlands

Dutch Kidney Foundation
Groot Hertoginnelaan 34
1405 EE, Bussum
The Netherlands

Laboratory Sites:
Leiden University Medical Center, The Netherlands
Radboud University Medical Center, The Netherlands

Objective:
To investigate whether intervention with the dietary supplement Endocalyx™ improves the
Microvascular Health Index between baseline and 3 months in type 2 diabetic South Asian patients with
microalbuminuria in comparison to the placebo group.

Bedside analysis of the sublingual microvascular glycocalyx in the emergency room and intensive care unit – the GlycoNurse study

Alexandros Rovas, Alexander-Henrik Lukasz, Hans Vink, Marc Urban, Jan Sackarnd, Hermann Pavenstädt, Philipp Kümpers
Scandinavian Journal of Trauma Resuscitation and Emergency Med . 2018

Abstract

Background: Deterioration of the endothelial glycocalyx (eGC), a protective carbohydrate-rich layer lining the luminal surface of the endothelium, plays a key role in vascular barrier dysfunction and eventually organ-failure in systemic inflammatory response syndrome and sepsis. Early detection of glycocalyx damage could thus become an important goal in critical care. This study was designed to determine the feasibility and reproducibility of quantitative, real-time glycocalyx measurements performed at bedside in the emergency room (ER) and intensive care unit (ICU).

Methods: The observational study included 70 patients admitted to the ER or ICU of a university hospital. A physician and the nurse in charge of the patient performed sublingual microcirculatory measurements using sidestream dark field (SDF) imaging. A novel data acquisition and analysis software (GlycoCheck™) was used to analyze the perfused boundary region (PBR), an inverse parameter of endothelial glycocalyx dimensions in vessels with diameters of between 5 and 25 μm.

Results: The method showed a good intra-observer reproducibility. Specifically, intraclass correlation coefficient analysis showed an excellent reproducibility between the physician’s measurements (0.77 [CI 95%: 0.52-0.89]). The bias between the two PBRs was – 0.077 ± 0.24 μm. Moreover, there were no significant differences in the PBR values obtained by the nurses when compared to those reported by the physician (regarded as the “gold standard” measurement). Intraclass correlation coefficient analysis showed excellent reproducibility between the nurses’ and physician’s PBRs (0.75 [95% CI: 0.52-0.87]). The mean difference between the two PBRs (i.e., the bias) was 0.007 ± 0.25 μm. The nurses’ PBR assessment had a 90% sensitivity (95% CI: 60-99%) and 90% specificity (95% CI: 80-93%) to identify a severely impaired glycocalyx.

Conclusion: Glycocalyx dimensions can be measured at patients’ bedside precisely by non-invasive assessment of the PBR. This assessment could become part of standard monitoring and contribute to clinical decision-making and resuscitation protocols in clinical trials and daily practice.

Early Onset Preeclampsia Is Associated With Glycocalyx Degradation and Reduced Microvascular Perfusion

Tracey L Weissgerber, Oscar Garcia-Valencia, Natasa M Milic, Elizabeth Codsi, Hajrunisa Cubro, Meryl C Nath, Wendy M White, Karl A Nath, Vesna D Garovic
Journal of the American Heart Association

Abstract

Background The endothelial glycocalyx is a vasoprotective barrier between the blood and endothelium. We hypothesized that glycocalyx degradation is present in preeclampsia, a pregnancy-specific hypertensive disorder characterized by endothelial dysfunction and activation. Methods and Results We examined the sublingual glycocalyx noninvasively using sidestream dark field imaging in the third trimester among women with normotensive pregnancies (n=73), early (n=14) or late (n=29) onset preeclampsia, or gestational diabetes mellitus (n=21). We calculated the width of the glycocalyx that was permeable to red blood cells (called the perfused boundary region, a measure of glycocalyx degradation) and the percentage of vessels that were filled with red blood cells ≥50% of the time (a measure of microvascular perfusion). In addition, we measured circulating levels of glycocalyx components, including heparan sulfate proteoglycans, hyaluronic acid, and SDC1 (syndecan 1), in a subset of participants by ELISA . Repeated-measures ANOVA was performed to adjust for vessel diameter and caffeine intake. Women with early onset preeclampsia showed higher glycocalyx degradation, indicated by a larger perfused boundary region (mean: 2.14 [95% CI, 2.05-2.20]), than the remaining groups (mean: normotensive: 1.99 [95% CI, 1.95-2.02], P=0.002; late-onset preeclampsia: 2.01 [95% CI, 1.96-2.07], P=0.024; gestational diabetes mellitus: 1.97 [95% CI, 1.91-2.04], P=0.004). The percentage of vessels that were filled with red blood cells was significantly lower in early onset preeclampsia. These structural glycocalyx changes were accompanied by elevated plasma concentrations of the glycocalyx components, heparan sulfate proteoglycans and hyaluronic acid, in early onset preeclampsia compared with normotensive pregnancy. Conclusions Glycocalyx degradation and reduced microvascular perfusion are associated with endothelial dysfunction and activation and vascular injury in early onset preeclampsia.