Endothelial dysfunction has been considered in the pathogenesis of obesity widespread in the population. The purpose of this review was to provide updated information about pathogenetic features and markers of endothelial dysfunction in obese patients. We mentioned systemic disorders in obesity, such as oxidative stress, an increase in pro-inflammatory cytokines – tumor necrosis factor alpha, interleukin-6, and arginase activity. We also discussed the role of insulin resistance in the development of endothelial dysfunction, as well as the product of adipose tissue metabolism – monocyte chemoattractant protein-1. The participation of perivascular adipose tissue, hyperoxia of adipose tissue in the regulation of inflammation was considered. We illustrated the influence of atherogenic concentrations of oxidized low-density lipoproteins, the asymmetric dimethyl-L-arginine level on endothelial function. Changes in laboratory parameters were analyzed: endothelin-1, levels of microalbuminuria, homocysteine and uric acid. We also described cytological (circulating vascular cells, endothelial microparticles) and instrumental (endothelium-dependent vasodilation, peripheral arterial tonometry, intima-media complex thickness of the common carotid artery, ultrasound kidneys examination with duplex scanning of the renal arteries) methods for assessing endothelial function. Factors that influence the risk of cardiovascular complications were arterial hypertension and arterial stiffness, high levels of low-density lipoprotein and triglycerides, reduced physical activity. The determination of endothelial function in patients with obesity can be important for predicting the pathology of the cardiovascular system. Information on the assessment of markers of endothelial dysfunction in such patients may expand the possibilities of early diagnosis and prevention of cardiovascular complications.

In chronic lower limb ischemia, the deep femoral artery plays a significant role in compensating for blood circulation due to the developed collateral branches providing the blood supply to the entire limb when a superficial femoral artery occluded. Surgical plasty of the deep femoral artery, profundaplasty, has been established as a technique having long-term patency results, significantly superior to bypass operations on the femoral-popliteal-tibial segment, as well as endovascular operations. However, the clinical effectiveness of isolated deep femoral artery is often questioned, especially in patients with critical ischemia. Nowadays there are no instrumental methods to reliably assess the quality of collaterals preoperatively. The article provides an overview of published data concerning different methods of profundaplasty improving effectiveness of surgical strategy through various technical modifications. Also it is introduced the role of the plain balloon angioplasty and stenting of the deep femoral artery. It also describes existing methods for isolated profundoplasty effectiveness preoperative evaluation.

Introduction. The development of diagnostic techniques of diabetes mellitus microvascular complications is an urgent task. One such method is laser Doppler flowmetry (LDF). Purpose was to analyze the correlations of clinical and laboratory parameters and LDF spectral parameters in patients with type 2 diabetes mellitus. Materials and methods. The study involved 50 patients with type 2 diabetes and diabetic foot syndrome. Microcirculation was assessed using the BIOPAC LDF 100C system. In parallel, monitoring of transcutaneous oximetry in the probed area was carried out using the TCM400 device. For correlation analysis, the Spearman correlation coefficient was used. Results. While studying, a positive correlation was noted between the contribution of pulse fluctuations and the duration of diabetes (p<0.05). For the level of glycosylated hemoglobin, it was positively correlated with the value of the contribution of pulsed fluxmotions and negatively correlated with the contribution of low-frequency fluxmotions and the fluxmotion index (p<0.05). When assessing transcutaneous oxygen tension, a negative correlation was found with the value of the contribution of pulse fluxmotions (p<0.05). These correlations can be explained in the light of modern concepts of the pathogenesis of type 2 diabetes mellitus microvascular complications. Conclusion. In the course of the work, spectral parameters of LDF were found correlated with clinical, laboratory, and instrumental parameters. The dynamics of changes in LDF parameters corresponds to the ideas about the pathogenesis of diabetic microangiopathy. A promising direction for further research is the study of the progressive development of diabetic microangiopathy and the role of individual pathogenetic factors in this process.

Introduction. The relationship between kidney dysfunction and cardiovascular system is multifaceted. Thus, the value of such a potential marker of glomerular filtration rate (GFR) as cystatin C cannot be underestimated as a predictor of the development of cardiovascular complications and atherogenesis factor in diabetes mellitus (DM) and chronic kidney disease (CKD). Objective was to evaluate the role of cystatin C as an atherogenesis factor in patients with DM and CKD. Materials and methods. The study involved 514 patients aged 25 to 80 years (the group of interest (n=449), the control group (n=65)). All patients underwent clinical and laboratory tests, sonography of the lower extremities vessels and brachiocephalic arteries (BCA). Results. The thickness of the intima-media complex increased with an increase of cystatin C level in the right carotid artery (CA) (from 0.80 [0.70; 0.90] mm to 0.97 [0.90; 1.02] mm) and in the left CA (from 0.90 [0.80; 0.94] mm to 0.92 [0.90; 1.10] mm). Logistic regression analysis demonstrated that an increase of cystatin C level > 0.93 mg/l raises the risk of intima-media thickening by 2.5 times (OR 2.505, p=0.042) and by 5 times when increase of cystatin C>1.38 mg/l (OR 4.718, p=0.001). At the same time, the association with homocysteine was unreliable (p=0.058). The level of cystatin C ≥0.82 mg/l with a sensitivity of 72 % and a specificity of 52 % allowed to predict the development of subclinical atherosclerosis in patients with DM and CKD (ROC AUC – 0.739). Conclusion. Cystatin C is not only a highly sensitive and accurate indicator of GFR, capable of detecting early stages of renal dysfunction, but also a highly effective predictive marker of atherosclerotic process in patients with DM and CKD.

Introduction. Patient frailty, having muscle hypotrophy as the main component, is important in determining the treatment tactics of cardiovascular diseases due to a decrease in the physiological reserve. An objective assessment of dystrophic changes level in the total muscle mass is possible by measurig the cross-sectional area of the psoas muscle (PMA). Аim was to determine if the psoas muscle area (PMA) could predict adverse outcomes and to investigate its utility in patients after transcatheter aortic valve implantation (TAVI). Materials and methods. The study included 51 patients with critical symptomatic aortic stenosis and high risk factors according to EuroScore II and STS. The study is a retrospective, single-centre analysis of the association of PMA from preoperative multislice computed tomography with adverse outcomes after TAVI. PMA was calculated as the average area of the left and right psoas. PMA measurements were then normalized to the patient’s body surface area (m2) and showed as psoas muscle index (iPMA; cm2/m2). Results. The mean age of the patients was 78.2±9.3 years, where 29 (56.9 %) were women. Since iPMA was not normally distributed, median values were analyzed: median iPMA for men 4.35 cm2/m2 and for women 3.55 cm2/m2. In our study, we found that iPMA was lower in patients with an early adverse outcome than in patients without an early adverse outcome (3.21±0.42 vs 5.47±0.43 cm2/m2; p=0.017). Patients with low iPMA (62.8 %) required longterm hospitalization, and low iPMA can be considered a predictor of higher hospital resource costs (p=0.056). Conclusion. Our study demonstrated that computed tomography-calculated iPMA is a simple and objective predictor of early postoperative complications and prolonged hospital stay after TAVI, and consequently higher hospital resource costs.

Introduction. The COVID-19 impact on hemostasis of stroke survivors with community-acquired pneumonia is an urgent problem. The aim of the study is to analyze the features of clinical and laboratory parameters in cerebral stroke combined with community-acquired pneumonia caused by the SARS-Co-V-2 virus. Materials and methods. The instrumental and laboratory examination results of 88 patients aged 73.0 (12.3) years in the acute period of stroke with community-acquired viral pneumonia symptoms were analyzed. The present study included 39.8 % (n=53) male and 60.2 % female (n=35) with duration of diagnosed infectious disease less than 7 days. The symptoms of cerebral stroke were compared with the results of laboratory testing of the hemostasis system, lipid metabolism, and the activity of the systemic inflammatory response. The severity of lung tissue damage and the outcomes of the diagnosed changes were assessed. Results. All patients had mild or moderate COVID-19. In 87.5 % (n=77) cases unspecified (40.2 %, n=31), cardioembolic (36.4 %, n=28), lacunar (3.9 %, n=3) and atherothrombotic (19.5 %, n=15) ischemic stroke subtype was diagnosed. Focal ischemia lesion in the left middle cerebral artery (LMCA) territory was detected in 45.6 % (n=35), in the right middle cerebral artery (RMCA) territory in 41.6 % (n=32). Manifestations of hemorrhagic stroke were noted in 12.5 % (n=11) with signs of parenchymal hemorrhage in 54.5 % (n=6), ventricular hemorrhage in 27.3 % (n=3), subarachnoid hemorrhages were noted in 18.2 % (n=2). The indicators of the coagulation system in terms of the number of platelets corresponded to 251.3 (90.7); the APTT value was in the range of 29.2 (26.7 33.0) (s); the INR parameter was 1.16 (1.05 1.25); the value of prothrombin ( %) corresponded to the value of 85.9(23.4). Conclusion. We do not observe the great disorders of haemostasis in the most acute period of the stroke. When combined with COVID-19 the most common stroke is ischemic stroke. The stroke survivors with the community-acquired pneumonia caused by SARS-CoV-2 laboratory tests show that increase of inflammatory markers are above the reference range.

Introduction. COVID-associated coagulopathy is an important pathogenetic factor in the development of new coronavirus infection (NCI) complications. Therefore the use of anticoagulants is considered as one of the fundamental components of the therapy of NCI. The aim of the study was to find the optimal anticoagulant therapy regimen in patients with severe NCI. Materials and methods. The study is retrospective and included an analysis of 947 cases of confirmed NCI. A survival analysis was performed with the construction of Kaplan-Meyer curves in order to assess the effect of a particular anticoagulant therapy regimen on the occurrence of thrombosis, bleeding, and death. In order to exclude the influence of cofounders due to the retrospective nature of the study, the pseudorandomization method («propensity score matching») was used, followed by the re-construction of Kaplan-Meyer curves. Results. Among 947 patients with severe COVID-19, 27 thrombotic events were verified in 24 patients and 44 hemorrhagic incidents in 38 patients. The day of the event, regardless of the choice of the starting point (the onset of the disease or the 1st day of hospitalization) and its nature (thrombosis or bleeding), had no statistical differences (p=0.33 and p=0.12, respectively). The use of a particular anticoagulant therapy regimen did not significantly affect the development of thrombosis, bleeding or death, including the use of the propensity score matching method. Conclusion. Thus, using therapeutic doses of anticoagulants in COVID-19 patients does not give advantages over the use of preventive doses concerning the risk of thrombosis, bleeding and death.

Aim – to study the functional state of the microvessels of the forearm skin in the acute phase of COVID-19 using the LDF method. Materials and methods. The study included 53 patients of moderate COVID-19. During the first day of hospitalization, all patients underwent LDF with amplitude-frequency Fourier analysis of tissue perfusion fluctuations using a portable LDF device with remote data transmission via Bluetooth protocol. The comparison group (CG) consisted of 28 healthy subjects matched in age and gender. Results. Patients in the acute phase of COVID-19, relative to CG, are noticed a decrease in the amplitude of endothelial vasomotions (Ae) – 0.0149 and 0.0198 PU (p<0.00005), an increase in the amplitude of myogenic vasomotions (Am) – 0.078 and 0.061 PU (p<0.01), an increase in the amplitude of blood flow pulse oscillations – 1.38 and 1.18 PU (p<0.01) and an increase in respiratory related blood flow oscillations – 0.48 and 0.29 PU (p<0.000001) respectively. Conclusion. The systemic inflammatory process in the acute phase of COVID-19 at the level of the skin microvasculature is characterized by: 1) vasomotor dysfunction of the endothelium; 2) a decrease of the perfusion efficiency of the endothelial regulation mechanism; 3) a decrease of the basal tone of smooth muscle cells of precapillary arterioles and capillary sphincters; 4) an increase of arterial blood flow to the capillary bed; 5) violation of the blood outflow from the microvasculature with the development of venular plethora.

Introduction. Successful translating of the fundamental research results into clinical practice is determined by a sufficiently large number of components, including the age of experimental animals and the anesthesia used. Chloral hydrate is often used as an anesthetic in preclinical studies, while its effect on the morphofunctional characteristics of the hippocampus in aged animals remains unexplored, which can lead to significant distortion and incorrect interpretation of the obtain results. Objective – morphofunctional assessment of the neurons and microglia in the layers of CA1, CA2, CA3 and CA4 fields of the hippocampus in aged rats anesthetized with chloral hydrate. Materials and methods. Male Wistar rats at the age of 24 months were anesthetized with chloral hydrate (400 mg/kg). In the early (2 days) period after chloral hydrate anesthesia, the morphofunctional state of neurons and the reaction of microglia were qualitatively and quantitatively assessed by histological, immunohistochemical, and morphometric analysis in the marginal, pyramidal, and molecular layers of fields CA1, CA2, CA3, and CA4 of the hippocampus. Results. 48 hours after 24-month-old Wistar rats were anesthetized with chloral hydrate, changes in the morphofunctional state of the pyramidal layer of the hippocampus were shown to be characterized by a significant decrease in the number of neurons in fields CA1 and CA3 with two nucleoli by 42 and 54 %, respectively, and a decrease in the width of the layer of fields CA1 and CA3 and CA4 by 27, 29 and 21 %, respectively, compared with similar indicators in the control group (P<0.05). In all layers of fields CA1, CA2, CA3 and CA4 of hippocampus, microglia reacted by the transformation of Iba-1-positive microgliocytes body and processes and a significant increase of the Iba-1 protein expression compared to the animals without administration of chloral hydrate (P<0.05). Conclusions. A single chloral hydrate dose administration necessary to anesthetized the aged Wistar rats without model surgery leads to morphofunctional changes in neurons in the most vulnerable fields of the hippocampus with simultaneous activation of microglia in all fields. This circumstance must be taken into account when conducting basic research and preclinical studies.

Introduction. Chronic thromboembolic pulmonary hypertension (CTEPH) is the most common complication of pulmonary thromboembolism (PE). Fibrous remodeling of the pulmonary circulation vessels against the background of CTEPH leads to an irreversible increase of the vessel wall stiffness and the ineffectiveness of CTEPH treatment. The involvement of Janus kinase (JAK) in the regulation of vascular wall and lung tissue inflammation and fibrosis allows for the possible effectiveness of JAK 1,2 inhibitors (iJAK) in the course of CTEPH. Purpose – to study the antifibrotic effect of iJAK for the prevention and treatment of CTEPH. Materials and methods. The study was conducted on male Wistar rats. Modeling of CTEPH was performed by sequential embolization of the vascular bed with partially biodegradable sodium alginate microspheres. 2 weeks after the last administration of the microspheres, low, medium and high doses of iJAK were initiated. To assess the effectiveness of the substance, the following tests were used: treadmill test, echocardiography, cardiac catheterization with right ventricular (RV) manometry, histological examination of the lungs. Results. Animals undergone vascular embolization demonstrated decreased exercise tolerance at all observation points compared to healthy animals. The placebo group, in contrast with the group getting treatment and iJAK, was found to have an increased mean RV pressure compared to healthy animals. There was an increase in mean RV pressure in the placebo group (15.5±7.7 mmHg) and in the low dose and iJAK group (13.4±6.4 mmHg) compared with healthy animals (9.4±2.2 mmHg). Vascular hypertrophy of the pulmonary artery branches was lower in group getting average dosages and iJAK compared with the placebo group (54.9±19.0 and 68.9±23.1 %, respectively). Thus, the suppression by iJAK of aseptic inflammation and following fibrosis leads to the decreasing of severity of pulmonary circulation remodeling in the experimental model of CTEPH. This approach can be used in the comprehensive bypass and prevention of CTEPH.

Introduction. This model of skin acute inflammation caused by photodynamic damage (PHD), where reactive oxygen species (ROS) play a key role, enables the analysis of the microcirculation (MCC) dysfunction and degranulation of mast cells (MCs) at the site of exposure. The current study explored the IgE-independent mechanisms of MCs activation caused by PHD and the possibility of its pharmacological correction. Aim of the study – to evaluate the possibilities of using the model of acute inflammation induced by ROS during PHD to study the MCs contribution to the regulation of vascular permeability and to study angioprotective and MCC-improving drugs at the preclinical stage. Materials and methods. Male Wistar rats were injected with a photosensitizer, then anesthetized and laser irradiated 3 hours later, followed by one of the following drugs: hydrocortisone (HC), ethylmethylhydroxypyridine succinate (ES), or quinacrine (QC). Skin MCC was investigated by laser Doppler flowmetry. Calculation and morphometry of MCs was carried out on film preparations of loose connective tissue of the skin. Results. Immediately after PHD, the blood flow in the control group was 1.9 [1.4; 2.3] p. u., which is 55 % less than the initial values. Partial restoration of blood flow up to 3.7 [3.3; 4.0] p.u. was observed after one hour of observation (88 % of baseline, p<0.001). Despite the administration of HC and ES, the blood flow after PHD decreased by 8,5 and 32,5 %, respectively. After an hour, it was only 78 % of the baseline. Intravenous administration of QC immediately after irradiation, lead to decrease of the blood flow only 28 %, and after an hour the blood flow was completely restored. The degree of MCs degranulation after the intravenous administration of HC and QC is almost equal and characterized by a decrease in the number of MCs with complete (anaphylactic) degranulation to 27.5 [21.6; 29.4] and 26.4 [22.5; 32.5] %, respectively, versus 46.9 [47.7; 52] % in the control group (p<0,05); however, after the administration of ES, the results are comparable with the intact control. Non-parametric correlation analysis did not reveale statistically significant difference between blood flow one hour after photodynamic exposure and morphometric types of MCs in groups with various drugs. Conclusion. Differences between the drug effects on the skin blood flow and the IgE-independent MCs activation is confirmed by the absence of a correlation between these parameters. QC, in comparison with ES and HC, is more effective in relation to dysfunction of the skin MCC. Under these conditions, the combined use of anti-inflammatory and antioxidant drugs seems promising.