A modern concept of the endothelial dysfunction in the pathogenesis of many diseases includes the glycocalyx damage along with impaired of the morphology and function of endothelial cells. The glycocalyx is a gel-like submembrane complex of protein-carbohydrate, carbohydrate-lipid components and plasma molecules forming a three-dimensional network on the luminal surface of the endothelium. The features of the borderline location of endothelial glycocalyx in the vascular system determine various important functions: barrier, regulatory, anti-inflammatory, antithrombotic, mechanotransduction ones, etc. In recent years, due to the improvement of visualization methods endothelial glycocalyx structure has been detailed. Its physiological functions and the role in the development of some pathological conditions have been clarified. Modern methods of glycocalyx assessment include invasive and non-invasive research techniques. The most promising ones are dark-field microscopy and the determination of glycocalyx-associated biochemical markers. Endothelial glycocalyx damage is a universal pathogenetic component and the earliest marker of the development of most diseases. Therefore, the endothelial glycocalyx assessment refers to promising areas of research. The ability to correlate with other prognostic indicators allows us to consider the endothelial glycocalyx damage as a marker of the poor health prognosis. That is why, assessment of the endothelial glycocalyx condition will allow to personalize treatment and to prevent the diseases progression.

Introduction. The authors draw readers’ attention to markers of endothelial dysfunction in chronic kidney disease. Objective – to study changes in endothelial dysfunction indicators in patients undergoing program hemodialysis. Materials and methods. The study included 80 patients. The first group consisted of healthy volunteers in the amount of 40 people. The second group consisted of 40 patients who had been on program hemodialysis for more than one year. The following indicators of endothelial dysfunction were studied: intercellular adhesion molecules (Icam); angiotensin-II; adhesion molecules of the vascular endothelium (Vcam); selectin SL; Superoxide dismutase (Cu / Zn-SOD); dimethylarginine (ADMA); products of deep protein oxidation (AOPP); oxistat; endothelin-1 (1-21); C-reactive protein (CRP), endothelin synthase. Results. The level of serum Cu / Zn-SOD is statistically significantly increased relative to the control values in patients of two groups. The total level of AORP in the blood serum of patients with dialysis is statistically significantly higher than the control value. The minimum value of its level in healthy volunteers was 71.6 μmol/L, the maximum – 98.7 μmol/L. In dialysis patients, 78.6 and 391.0 μmol/L, respectively. A comparative analysis showed a significant increase in the levels of Icam, Vcam, ADMA, C-reactive protein, angiotensin-II in the serum of patients with dialysis relative to the values of the control group. Icam: 98.7 ng/ml – the minimum indicator in the group of healthy volunteers, 386.1 ng/ml – the maximum level in this group; 218.5 ng/ml is the lower level and 944.5 ng/ml is the maximum value in the group of dialysis patients. Vcam: 241.8 ng/ml – the minimum value in healthy volunteers is 941.6 ng/ml – maximum; 731.6 ng/ml is the minimum and 3451.1 ng/ml is the maximum in dialysis patients. Conclusions. The results of our study showed a statistically significant increase in all the studied parameters in the group of patients on program hemodialysis in comparison with healthy volunteers. The hemodialysis procedure causes certain biochemical changes in the patient’s body, which in turn lead to the development of oxidative stress and chronic inflammation.

The aim of the study was to study the associations between markers of endothelial dysfunction, systemic inflammation and platelet aggregation properties in patients with stable stenocardia. Materials and methods. 100 patients with stable stenocardia were examined, mean age 59.2 ± 6.9 years, who received double antiplatelet therapy (DAPT) in the form of acetylsalicylic acid (ASA) 75 mg and clopidogrel 75 mg. The obtained data (general clinical, aggregometry, level of C-reactive protein (CRP), soluble CD40 ligand, sP-selectin, von Willebrand factor (VF), endothelin-1 (ET-1), forearm blood flow (FBF studies)) were analyzed using STATISTICA 10.0 programs. Results. 45 % of patients with an insufficient response to DAPT (SG2) and 55 % with a normal response (SG1) were identified. The level of ET-1, PV, and CRP was higher in SG2, compared to SG1. FBF in SG1 – 2.4 [–8.9; 25.0] %, in SG2 – –8.4 [–19.2; 14.1] %, p <0.05. In SG2, patients with pronounced endothelial dysfunction (p = 0.024 according to Fisher’s exact test) predominated. Conclusions. DAPT with ASA and clopidogrel is effective in 55 % of patients with stable stenocardia. 45 % of patients have an insufficient response to DAPT. Laboratory resistance to DAPT in patients with stable stenocardia is multifactorial and is associated with high levels of CRP, ET-1, PV and a pronounced endothelial dysfunction. The presence of a pronounced decrease of FBF (OR 3.4; 95 % CI 1.2–9.3, p <0.05), elevated CRP values (OR 2.9; 95 % CI 1.2–6.8, p <0.05), can be used as a criterions for selecting patients to aggregometry.

Introduction. The key point of cardiorenal relationships is the activation of the renin-angiotensin-aldosterone system and the formation of endothelial dysfunction. The aim of our study was to assess the state of endothelium-dependent vasodilation (EDVD) in patients with chronic kidney disease (CKD) as a function of the glomerular filtration rate (GFR). Materials and methods. It was investigated 40 healthy men (mean age 39.2±2.0 years) and 72 patients with CKD I st. (mean age 42.5±11.9 years). GFR was calculated using the formula CKDEPI. Tissue perfusion was studied by high-frequency ultrasound Doppler. Vascular reactivity of the skin was evaluated in functional tests with ionophoresis of acetylcholine. Results. Compared with healthy individuals, the increase in the volumetric blood flow velocity at the 2 minute test with acetylcholine was reduced only at a GFR value of 90–109 ml/min/1.73 m², with large values of GFR, no indicator changes were detected. Also, only in these patients the most significant violations of oxidative status were noted in the form of an increase in the concentration of diene conjugates in the blood serum, a decrease in the concentration of tocopherol and general SH groups. Conclusions. Disturbance of endothelium-dependent vasodilation in the sample with acetylcholine in patients with the first stage of CKD was established with a GFR value of less than 109 ml/min/1.73 m². Disturbance of the indicators of oxidative status was noted with a GFR value of less than 109 ml/min/1.73 m².

Introduction. Тhe peripheral (PAD) arteries of lower extremities are most commonly suffers from the peripheral arterial disease that can be asymptomatic for a long time. Late clinical manifestation leads to reduction the quality of life and is often accompanied by limbs amputation. These cases are frequent when revascularization is not possible. The development of chronic limb ischemia (CLI) is associated with endothelial dysfunction (ED), oxidative stress and inflammation. The aim of this work is to study skin microcirculation and laboratory markers of ED in patients with PADs before and after medical treatment or operations. Materials and methods. The study included 17 healthy people (44–61 years old) and 38 patients (58–75 years old) with PAD, which were divided into four groups in accordance with the stage of CLI. The research protocol included biochemical and instrumental research methods to determine the functional status of the microcirculation system. Results. Significant differences in the values of biochemical markers and the results of instrumental studies of ED were obtained in groups with PAD compared with the control group. The study was fully repeated two weeks after treatment. It revеals that direct endovascular and reconstructive methods for revascularization of the lower extremities, simultaneous or staged elimination of the pathological focus, complex conservative therapy are accompanied by a decrease in laboratory markers of ED and inflammation and an improvement in micro vessel regulation due to the neurogenic and endothelial mechanisms. The most significant differences were obtained in the group with atherosclerosis of low limb vessels, namely the von Willebrand factor (from 180±56 % before the treatment to 128±36 % after), endothelin (0.37±0.15 pmol/l before the treatment to 0.20±0.08 pmol/l) after, homocysteine (from 15±3 mcmol/l to 10±2 mcmol/l). Conclusions. It was found that the recovery of the main blood flow is accompanied by an improvement in the function of the microcirculation system, which can be detected both by specific biomechanical markers and instrumental methods for diagnosing ED.

Introduction. The morphological and functional changes of the vascular wall endotheliocytes in case of essential arterial hypertension in elderly women are considered. They are due to the action of complex pathogenetic mechanisms of damage to the vascular wall, their dynamic changes with a chronic increase in blood pressure, against the background of endogenous inflammation and apoptosis, which have been little studied, which determines their relevance. The goal is to determine the importance of the processes of subclinical inflammation in the development and severity of endothelial injuries, apoptosis in hypertension in elderly patients. Materials and methods. The study involved 35 elderly women suffering from essential arterial hypertension of the II degree, II stage, who gave their consent to participate in the study. The degree of severity of endothelial dysfunction, which was established using dopplerography of the brachial artery by the linear method. The comparison group included 30 women with a normal level of blood pressure of a similar age without cardiovascular disease. The degree of dilatation of the brachial artery against the background of reactive hyperemia by more than 10% of the initial diameter was recognized as normal. The severity of subclinical inflammation was evaluated by the activity of TNF-α, HF CRP, the level of desquamated endotheliocytes, a blood test was performed using enzyme-linked immunosorbent assay (ELISA). Results. There was an increase in apoptotic activity (0.34±0.05 and 11.3±0.8), subclinical inflammation, and activation of proapoptotic receptors, which was 4 times higher (151.8±27.2 PG/ml) than in patients without this pathology (39.8±1.5 PG/ml). A strong direct correlation was found between the number of desquamated endothelial cellsendotheliocytemia and the degree of vasomotortonic dysfunction (r=0.62). In patients with arterial hypertension, the number of desquamated endothelial cells level of endotheliocytemia (1.91±0.05 cells/ml) is 1.5 times higher than in the comparison groupcontrols (1.1±0.02 cells/ml). Conclusion. With arterial hypertension in elderly patients, the formation of endothelial dysfunction has been established, its dynamic progression with increasing severity of tonic vasodilation disorders.

Introduction. Over the past three decades, the prevalence of overweight and obesity in the world has grown by almost 30–50% among adults and children. A number of metabolic and hemodynamic disorders, as well as the pathology of many organs and systems are often associated with obesity. The aim of our study was to compare the functional state of the endothelium in various variants of complicated obesity (СO). Materials and methods. The study included 66 people with СO whose average age was 47.3 ± 9.9 years, from this group 3 groups were formed depending on the complications of obesity (dyslipidemia, hypertension and impaired glucose tolerance). To assess the functional state of endothelium, we used the method of wavelet analysis of skin temperature fluctuations during cooling of the limb; endothelin-1 (ET-1), albuminuria (AC), and vascular endothelial growth factor (VEGF) were determined as markers of endothelial dysfunction. Results. The levels of VEGF, ET-1 and AC in the groups with СO did not differ significantly, however, they were significantly higher than in the comparison group. The results of the cold test revealed the absence of restoration of the amplitudes of fluctuations in skin temperature equally in all groups with CO compared with the control group (post-cold vasodilation indices (IPV) in group 1 – 0.45 (0.38–0.69, in group 2 – 0.59 (0.41–0.83), in group 3 – 0.66 (0.53–0.79), in the Control group – 0.91 (0.86–1.06), p<0.05). Correlations between biochemical and instrumental markers of endothelial dysfunction and insulin resistance indices were obtained: ET-1 correlated with insulin (r=0.49; p=0.02), HOMA index (r=0.55; p=0.01); AU value correlated with glycemia (r=0.70; p=0.02); The IVC vasoconstriction index correlated with the HOMA-IR index (r=0.62; p=0.05); The IPV-1 index decreased with increasing VEGF (r=–0.86; p=0.002) and HOMA-IR (r=–0.86; p=0.002). The IPV-2 index inversely correlated with the level of postprandial glycemia (r=–0.87; p=0.05), systolic blood pressure (r=–0.55; p=0.04), OT (r=–0.57; p=0.04) and ET-1 (r=–0.58; p=0.04). Conclusion. The unified basis of the revealed disorders in СO allows us to conclude that the factors of insulin resistance are complex: hyperglycemia, dyslipidemia, and arterial hypertension, which makes it difficult to identify the leading factor in the formation of endothelial dysfunction.

The aim of the work was to identify the relationship of vasomotor and angiogenic factors of the endothelium, as well as the state of the antioxidant system in rheumatoid arthritis (RA). Materials and methods included 50 patients with RA and 42 healthy people of appropriate age and gender, who analyzed the main clinical indicators. In erythrocytes, the activity of superoxide dismutase (SOD), glutathione peroxidase (GPO), glutathione reductase (GR) and the concentration of reduced glutathione (GSH) were investigated. The concentration of higher nitrogen oxides (NOx), endothelin-1 (ET-1) and vascular endothelial growth factor VEGF-A was determined in plasma. Results. In the general group of patients with RA, signs of oxidative stress (OS) were observed, expressed in a decrease in the activity of GPO, GR and SOD when compared with the control, and a positive correlation of ET-1 with VEGF-A (R=0.547, p=0.028) and ET-1 with RF ( R=0.578; p=0.024). ET-1 (R=0.622; p=0.031) and VEGF-A (R=0.627; p=0.016) correlated with the presence of joint erosion. Among patients with joint erosion, the level of VEGF-A correlated with the activity of the process (R=0.756; p=0.030), the level of plasma NOx (R=0.545; p=0.036) and the activity of GR (R=0.579; p=0.03). The ET-1 level in the blood plasma of patients with RA with joint erosion was 10.0 (4.4–10.0) ng / l and was higher than in patients without erosion (4.2 (2.3–17) ng/l). The level of plasma VEGF-A in patients with RA with joint erosion (62.8 (31.0–100.0) ng /l) was higher than in patients without erosion (20.4 (10.0–25.3) ng/l). Conclusions. A decrease in the concentration of GSH and the activity of GPO, GR and SOD indicate the presence of OS in patients with RA, regardless of the duration and activity of the disease. ET-1 and VEGF-A may be prognostic criteria for erosive RA.

Introduction. Due to unpredictability of stressors exposure, prevention of stress-induced coronary vascular tone disorders with new classes of drugs with pleiotropic action is quite relevant. At the present time, besides traditionally used vasoactive substances, benzimidazole derivatives with antioxidant and anti-inflammatory activity are considered. The goal of the present study is to test the hypothesis that infusion of the 2-ethyl-thiobenzimidazole hydrobromide (2-ETH) before stress is able to effectively prevent stress-induced disorders of coronary vascular tone and myocardial contractility disorders and clarify mechanisms of such 2-ETH action. Materials and methods. Coronary vascular tone and myocardial contractility were investigated using Langendorff isolated rat heart model. The ВКСа-channel inhibitor, tetraethylammonium (TEA) was added to the Krebs-Henseleit solution to the final concentration of 1 mM. Concentration of the stable products of NO degradation (NO2-/NO3-) was determined spectrophotometrically; activation of lipid peroxidation was assessed in the myocardium using a spectrophotometric method; concentration of iNOS, еNOS, and IL-1β was detected with enzyme-linked immunosorbent assay; concentration of C-reactive protein was estimated with immunoturbidimetric method. Results. 2-ETH pretreatment prevented stress-induced decrease in ВКСа-channels and eNOS activity, limited iNOS activity in coronary vessels and restored myocardial contractility. These 2-ETH’ effects together with its ability to prevent alterations of stress-sensitive organs and limit oxidative, nitrozative stress and systemic inflammation argue why 2-ETH should be considered as a useful tool for pathogenetic prevention of stress-induced pathology. Conclusions. 2-ETH should be considered as a useful tool for pathogenetic prevention of stress-induced pathology.

Introduction. Distinctive features of microcirculation and their connection with structural disorders in the skin during photodynamic exposure using various photosensitizers (PS) are not well understood. Objective. Comparative analysis of the relationship between morphological abnormalities and changes in blood flow in the skin during photoactivation of PS, taking into consideration the influence on mast cells (MC), structural elements of the dermis and underlying muscle tissue. Materials and methods. In this work were used male Wistar rats (n=46). PS were administered intravenously: Radachlorin (RDC) (5 mg/kg) 3 hours, Coproporphyrin III (CPP) (10 mg/kg) 24 hours before irradiation. To control the accumulation of PS in the skin, methods of fluorescence videodermatoscopy and confocal scanning laser microscopy (CSLM) were used. Laser irradiation (662 and 635 nm) was performed with an energy density of 50 Jcm^–2, the irradiated surface area was 0,78 cm². Laser Doppler flowmetry was used to assess microcirculation in the skin. Results. According to videodermatoscopy, fluorescence maximum values in the R channel were recorded 6-8 hours after administration, and amounted to 4901 [4190; 6732] a. u. for RDC and 2997 [2678; 3351] a. u. for CPP. Using the CSLM method, it was shown that CPP is poorly visualized in the walls of blood vessels. In experiments with RDC, the structures of areolar tissue of the hypodermis are determined. An hour after laser irradiation, in experiments with RDC, as well as with CPP, a significant decrease in blood flow was noted compared with the control to 3,61±0,7 and 4,27±1,4 PU, respectively. Structural changes when using both PS showed endothelial swelling, vasodilation and congestion, hemorrhages in the dermis, and underlying muscle tissue. The amount of MC was reduced. Conclusions. Laser irradiation with the parameters used in the work leads to a significant decrease in blood flow in the skin in experimental animals as a result of photoactivation of PS. CPP requires a higher radiation energy density. Morphological changes were revealed not only at the level of the epidermis, dermis and hypodermis, but also the underlying striated muscle tissue. In the early stages after exposure, massive degranulation of MC is noted with a decrease in their number.

The lecture analyzes modern data on the types, etiology, key stages of pathogenesis, manifestations and consequences of typical forms of regional blood flow and microcirculation disorders. The lecturer dwells on typical forms of regional blood flow (in medium vessels): pathological arterial hyperemia, venous hyperemia, ischemia, and stasis. The variants of ischemia associated with increased arterial inflow to tissue or organ are considered as compared to medium-normal inflow. The lecture provides data on typical hemolymph microcirculation disorders, including intravascular, transmural, extravascular disorders, as well as capillary-trophic insufficiency as a final result of one or more microcirculatory disorders. The blood sludge phenomenon is characterized as a pathology of the blood aggregate state, which is either a cause or a consequence of a microhemocirculation disorder. The lecture is recommended for students, medical residents, post-graduate students, and trainees of the system of post-graduate professional education at medical universities.