BACKGROUND: Endothelial glycocalyx (EG) plays a crucial role in maintaining the plasma proteins within the intravascular space. OBJECTIVE: We studied whether exogenous albumin protects the EG in an experimental model of EG enzymatic damage in rats. METHODS: Rats were divided into three groups of 10 animals that received (1) Evans blue (2) Evans blue + hyaluronidase, or (3) Evans blue + hyaluronidase + 20% human albumin via the tail vein. Spectrophotometric analysis was performed 2 h later to quantify the leakage of Evans blue-labeled albumin into the heart, lungs, brain, kidneys, liver, small intestine, spleen, and skeletal muscle. RESULTS: Administration of hyaluronidase numerically increased the capillary leakage of Evans blue in all examined tissues. Co-administration of albumin decreased the leakage of albumin in all tissues except the heart. In the lungs, the ratio between the absorbance and dry organ weight decreased from 5.3 ± 2.4 to 1.7 ± 0.5 (mean ± SD) (P < 0.002), and in the liver, the absorbance decreased from 2.2 ± 0.7 to 1.5 ± 0.4 (P < 0.011). CONCLUSION: Exogenous albumin decreased the capillary leakage of albumin which was interpreted as a sign of maintained EG integrity.
- MeSH
- albuminy * metabolismus MeSH
- cévní endotel účinky léků metabolismus MeSH
- Evansova modř MeSH
- glykokalyx * metabolismus účinky léků MeSH
- hyaluronoglukosaminidasa farmakologie MeSH
- kapilární permeabilita * účinky léků MeSH
- krysa rodu rattus MeSH
- lidé MeSH
- modely nemocí na zvířatech MeSH
- potkani Wistar MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- lidé MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
The clinical course of essential thrombocythemia (ET) is complicated with thrombosis which significantly impacts patients' mortality. Studies have identified JAK2V617F mutation as an independent risk factor for thrombosis. Circulating extracellular vesicles (EVs) were evaluated in several studies regarding myeloproliferative neoplasms and thrombosis as potential biomarkers. The present study investigates the relationship between JAK2V617F mutation and EVs levels in 119 ET patients. Our analyses revealed that JAK2V617F-positive patients are at a significantly increased risk of thrombosis within five years before the ET diagnosis (hazard ratio [95% CI]: 11.9 [1.7-83.7], P = 0.013), and that JAK2V617F mutation is an independent risk factor for thrombosis at ET diagnosis or during the follow-up (hazard ratio [95% CI]: 3.56 [1.47-8.62], P = 0.005). ET patients have higher levels of platelet-EVs, erythrocyte-EVs and procoagulant activity of EVs than the healthy population. Absolute and relative counts of platelet-EVs are increased in the presence of JAK2V617F mutation (P = 0.018, P = 0.024, respectively). In conclusion, our results support the role of JAK2V617F mutation in the pathogenesis of thrombosis in essential thrombocythemia through enhancing platelet activation.
BACKGROUND: Hydrogen is a potent antioxidant agent that can easily be administered by inhalation. The aim of the study was to evaluate whether hydrogen protects the endothelial glycocalyx layer after successful cardiopulmonary resuscitation (CPR). METHODS: Fourteen anesthetized pigs underwent CPR after induced ventricular fibrillation. During CPR and return of spontaneous circulation, 2% hydrogen gas was administered to seven pigs (hydrogen group) and seven constituted a control group. Biochemistry and sublingual microcirculation were assessed at baseline, during CPR, at the 15th, 30th, 60th, 120th minute. RESULTS: All seven subjects from the hydrogen group and six subjects in the control group were successfully resuscitated after 6-10 minutes. At baseline, there were no statistically significant differences in examined variables. After the CPR, blood pH, base excess, and lactate showed significantly smaller deterioration in the hydrogen group than in the control group. By contrast, plasma syndecan-1 and the measured variables obtained via sublingual microcirculation did not change after the CPR; and were virtually identical between the two groups. CONCLUSION: In pigs, hydrogen gas inhalation during CPR and post-resuscitation care was associated with less pronounced metabolic acidosis compared to controls. However, we could not find evidence of injury to the endothelium or glycocalyx in any studied groups.
- MeSH
- endotel MeSH
- glykokalyx MeSH
- kardiopulmonální resuscitace * MeSH
- lidé MeSH
- modely nemocí na zvířatech MeSH
- prasata MeSH
- reperfuzní poškození * MeSH
- srdeční zástava * terapie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: The sidestream dark-field imaging method is used to study microcirculation. Normal values of sublingual microcirculation parameters in healthy children of different age and gender categories are unknown. OBJECTIVE: The study's main goal was to determine normal values of selected parameters of sublingual microcirculation in healthy children of different age and gender categories. METHODS: 40 healthy children were measured, ten aged 3-5.9 years, ten aged 6-10.9 years, ten aged 11-14.9 years, and ten aged 15-18.9 years. After recording the basic anthropometric parameters and vital functions, each volunteer had their microcirculation measured using an SDF probe placed sublingually. Three video clips were recorded and processed offline, and the three best and most stable parts of each were analyzed. RESULTS: Total vascular density, small vessel density, proportion of perfused small vessels, perfused vessel density, perfused small vessel density, and DeBacker's score were significantly higher in females than in males. There were no differences between age groups in microcirculation parameters except MFI. CONCLUSIONS: Age does not influence normal values of microcirculatory parameters. Female gender was associated with higher vessel density, perfused vessel density, and DeBacker's score. A suggestion of the normal range of microcirculatory parameters in healthy children is provided.
- MeSH
- dítě MeSH
- dobrovolní pracovníci * MeSH
- lidé MeSH
- mikrocirkulace MeSH
- ústní spodina * krevní zásobení MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Coronavirus disease (COVID-19) associated endotheliopathy and microvascular dysfunction are of concern. OBJECTIVE: The objective of the present single-center observational pilot study was to compare endothelial glycocalyx (EG) damage and endotheliopathy in patients with severe COVID-19 (COVID-19 group) with patients with bacterial pneumonia with septic shock (non-COVID group). METHODS: Biomarkers of EG damage (syndecan-1), endothelial cells (EC) damage (thrombomodulin), and activation (P-selectin) were measured in blood on three consecutive days from admission to the intensive care unit (ICU). The sublingual microcirculation was studied by Side-stream Dark Field (SDF) imaging with automatic assessment. RESULTS: We enrolled 13 patients in the non-COVID group (mean age 70 years, 6 women), and 15 in the COVID-19 group (64 years old, 3 women). The plasma concentrations of syndecan-1 were significantly higher in the COVID-19 group during all three days. Differences regarding other biomarkers were not statistically significant. The assessment of the sublingual microcirculation showed improvement on Day 2 in the COVID-19 group. Plasma levels of C-reactive protein (CRP) were significantly higher on the first two days in the COVID-19 group. Plasma syndecan-1 and CRP were higher in patients suffering from severe COVID-19 pneumonia compared to bacterial pneumonia patients. CONCLUSIONS: These findings support the role of EG injury in the microvascular dysfunction in COVID-19 patients who require ICU.
- MeSH
- biologické markery MeSH
- COVID-19 * patologie MeSH
- endoteliální buňky * patologie MeSH
- glykokalyx * metabolismus MeSH
- lidé středního věku MeSH
- lidé MeSH
- pilotní projekty MeSH
- prospektivní studie MeSH
- senioři MeSH
- syndekan-1 metabolismus MeSH
- umělé dýchání MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- pozorovací studie MeSH
BACKGROUND: The endothelial glycocalyx (EG) plays a vital role in the physiology and pathophysiology of human microcirculation. Having relevant EG damage model would be important tool for testing new interventions aiming at EG protection and recovery. We describe the first in vivo EG damage model in pig. OBJECTIVE: To investigate the course of animal EG damage induced by specific enzymes. MATERIAL AND METHODS: Four anesthetized piglets received enzymes: 1g hyaluronidase and 25 IU heparanase I intravenously. Blood and urine samples were collected at baseline and 20/40/60/80/100/120 min for detecting markers of endothelial and EG function. Sublingual microcirculation and EG thickness were assessed by Side-stream Dark Field (SDF) imaging and Perfused Boundary Region (PBR) respectively. EG of the mesentery artery was visualized in fluorescent microscopy. RESULTS: Biochemical marker of EG damage syndecan-1 showed temporary increase with return to baseline and was reflected by PBR values. Albumin levels suggested brief period of capillary leakage (decrease in the serum, increase in the urine) with a trend to normalization. Urine glycosaminoglycans peaked at 120 minutes. Microcirculatory perfusion parameter showed significant alteration. Diffusion parameters were altered with no statistical significance. CONCLUSION: EG damage induced by specific enzymes was reflected by temporary changes of biochemical makers together with alteration of microcirculation and changes in fluorescent microscopy of EG layer. Our results support to further validate presented model of EG damage on a larger number of animals.
- MeSH
- glykokalyx * MeSH
- kapiláry MeSH
- mikrocirkulace MeSH
- pilotní projekty MeSH
- prasata MeSH
- trávení MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND + OBJECTIVE:Age-related macular degeneration (AMD) is the most common cause of practical blindness in people over 60 years of age in industrialised countries. We formulated a hypothesis that a group of initial laboratory parameters would be suitable for prediction of prognosis of AMD, allowing for individual modifications in treatment intensity. PATIENTS AND METHODS: 66 patients with dry form of AMD were treated using rheohaemapheresis with an individual follow-up period of more than 5 years. The patients' initial laboratory data was split in two subgroups based on treatment success and analysed using discriminant analysis (analysis of the linear and quadratic models using the automated and interactive step-wise approach) by means of the Systat 13 software. RESULTS: Prediction of prognosis based on the initial laboratory parameters was correct in 79% of unsuccessfully treated patients, allowing for early detection of high-risk patients. With the use of a quadratic model, the prediction was correct in 100% of unsuccessfully treated patients and in 75% of successfully treated patients. CONCLUSION: Implementation of discriminant analysis is a promising method for prediction of prognosis, especially when the patient is at risk of AMD progression, which allows for early and more intensive monitoring and treatment.
BACKGROUND: Endothelial glycocalyx (EG) is a carbohydrate-rich gel-like mesh covering the apical surface of endothelial cells. It has been linked to the microvascular pathophysiology and tissue metabolism. However, little is known about its condition in young healthy adults. OBJECTIVE: We aimed to describe the condition of EG in young healthy adults by in vivo EG imaging and measurement of syndecan-1, a plasma marker of EG integrity in order to obtain reference values. METHODS: For in vivo EG studies we used Side-stream Dark Field imaging of the sublingual microcirculation. Recordings were analysed automatically by GlycoCheck software providing the Perfused Boundary Region (PBR) as a marker of EG thickness. Levels of syndecan-1 were analysed in plasma samples by ELISA. RESULTS: 21 volunteers were included in the study. Median of the PBR value was 1.82 μm (interquartile range 1.69-2.01, 95% CI 1.79-1.97). Median concentration of syndecan-1 was 0.3 ng/ml (interquartile range 0.23-0.39, 95% CI 0.27-0.49). CONCLUSION: This study provides a comparison for cohorts of patients with a particular disease where the EG is presumably damaged. Our findings do not entirely comply with already published data in healthy individuals.
- MeSH
- biologické markery metabolismus MeSH
- dospělí MeSH
- endoteliální buňky metabolismus MeSH
- glykokalyx metabolismus MeSH
- lidé MeSH
- mladý dospělý MeSH
- zdraví dobrovolníci pro lékařské studie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Endothelial glycocalyx (EG) is a carbohydrate-rich vascular lining of the apical surface of endothelial cells. It has been proved to have an essential role in vascular homeostasis. Lipid emulsions as part of parenteral nutrition (PN) are widely used in patients in the setting of critical care and perioperative medicine. Due to their structure, lipids may potentially interact with EG. The aim of the study was to evaluate the effect of lipid emulsion on EG. OBJECTIVE: To assess the influence of lipid emulsion on EG integrity in ICU patients using a videomicroscopic and biochemical methods. METHODS: Patients in surgical ICU after major abdominal surgery or cardio surgery and in general ICU were assessed for eligibility for this pilot observational study in University Hospital. The study was performed during the first day of adding lipids as a part of their PN. The patients were given the SMOFlipid 20% for 6 hours in prescribed dose of approx. 1 g/kg of body weight. EG integrity was measured indirectly by automated sublingual videomicroscopy calculating a parameter PBR which describes the amount of lateral deviation of red blood cells from the central column and by levels of syndecan-1 and syndecan-4 in plasma as EG degradational products. Measurements were performed before lipid administration (T0) and 30 minutes after (T6) the infusion of lipid emulsion was completed. The statistical analysis was performed at the level of significance p < 0.05, data are expressed as mean ± standard deviation (SD) and for PBR as median and interquartile range (IQR). RESULTS: Fifteen patients were studied, from them 9 included in final analysis. PBR (expressed in μm) increased after the lipid infusion with no statistical significance (T0 = 2.10; 1.97-2.33 vs. 2.28; 2.11-2.45, p = 0.13). At T6 both syndecans showed statistically significant decrease in their particular levels. Syndecan-1 at T0 = 2580±1013 ng/l, resp. at T6 = 2365±1077 ng/l, p = 0.02; syndecan-4 at T0 = 134±29 ng/l, resp. at T6 = 123±43 ng/l, p = 0.04. CONCLUSION: In our study, we showed that six hours long SMOFlipid 20% infusion had no detrimental effect on the EG integrity as assessed by PBR value and by syndecan-1 and syndecan-4 plasmatic levels. Observed decrease of syndecans shortly after lipid infusion allows us to hypothesize even possibly protecting effect of lipids on EG.
- MeSH
- dospělí MeSH
- emulgační látky terapeutické užití MeSH
- endoteliální buňky metabolismus MeSH
- glykokalyx metabolismus MeSH
- jednotky intenzivní péče MeSH
- lidé středního věku MeSH
- lidé MeSH
- lipidy terapeutické užití MeSH
- mladiství MeSH
- mladý dospělý MeSH
- pilotní projekty MeSH
- prospektivní studie MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- videomikroskopie metody MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Damage of the endothelial glycocalyx (EG) has been described during surgery, but the effect of different anesthesia techniques remains unknown. Perfused boundary region (PBR) evaluated by side-stream dark field (SDF) imaging of the sublingual microcirculation enables in vivo EG assessment. PBR values are inversely related to the EG thickness. OBJECTIVE: The aim of the observational study was to evaluate the changes of PBR in patients undergoing elective joint surgery under general (GA) vs. neuraxial anesthesia (NA). Our hypothesis was that PBR will be lower in patients in NA. METHODS: Sixty consecutive patients (ASA 1-3) undergoing elective total knee or hip replacement under GA or NA were included in this prospective observational cohort study. PBR in the sublingual microcirculation was recorded in each patient using SDF at two time points - before surgery and 2 hours after surgery. RESULTS: Before surgery, there was no significant difference in baseline PBR between groups (NA: 1.95 μm (±0.24); GA: 2.02 μm (±0.26); p = 0.098). Postoperatively (2 hours after surgery) PBR was significantly increased in both groups with respect to baseline values (NA: 2.09 μm (±0.19), GA: 2.20 μm (±0.25); p < 0.001). In the GA group, postoperative PBR values were significantly higher than in the NA group (p = 0.006). CONCLUSION: Joint surgery led to significant increases of PBR. Patients in the GA group had significantly higher PBR values 2 hours after surgery compared to NA group. This might implicate that NA is associated with less EG damage then GA in elective hip/knee surgery.
