The review discusses published data on the effect of hydrogen sulfide on the functioning of the cardiovascular system. Hydrogen sulfide has become the third gas molecule, along with NO and CO, which was classified as gasotransmitters – signaling molecules, a unique feature of which is their ability to easily penetrate the cell membrane due to their good solubility in lipids. Signal transduction with the participation of gasotransmitters significantly differs from classical concepts – there is no need for either special membrane receptors or transport systems, gasotransmitters realize their effect practically in the zone of their biosynthesis, which makes such regulation fast and accurate. In the cardiovascular system, hydrogen sulfide has shown a pronounced cardioprotective effect, especially pronounced in conditions of hypertension and myocardial ischemia. Along with NO, hydrogen sulfide is the most important regulator of vascular tone, while it affects both the properties of the endothelium and regulates the contractility of vascular smooth muscle cells. The role of H₂ S in the pathogenesis of arterial hypertension and the therapeutic potential of this gasotransmitter and its derivatives in arterial hypertension treatment both in animal models and in clinical studies have been demonstrated. Experimental data confirming the participation of hydrogen sulfide in the processes of angiogenesis and in the pathogenesis of atherosclerosis were published. For the cardiovascular system, the main function of which is the oxygen supply to organs and tissues, the ability of this gasotransmitter to influence the blood system and act as an oxygen sensor seems to be important. Hydrogen sulfide affects the functional properties of platelets, thrombus stability and microvascular thrombolysis; there is experimental evidence of the effect of H₂S on the microrheological properties of erythrocytes and the process of erythrogenesis. And although the mechanisms of the effect of hydrogen sulfide have not yet been sufficiently studied, there is evidence that all gasotransmitters are in close interaction and their joint action gives a synergistic effect.

Introduction. Blood microcirculation and its microrheologic properties are impaired in cardiovascular diseases. Microrheologic properties are characterized by the red blood cells (RBC) ability to aggregate and disaggregate. Therefore, the correlation studies between RBC aggregation and microcirculation disorders in pathologies are of interest for the development of theoretical concepts related to blood flow and for clinical practice.

Aim. To analyze the correlation between capillary blood flow parameters measured in vivo and microrheologic blood parameters measured in vitro in patients suffering arterial hypertension (AH) and coronary heart disease (CHD).

Materials and methods. We studied 3 groups of people: patients suffering AH, patients suffering AH+CHD and healthy donors. The characteristic aggregation time and aggregation index were measured in vitro by laser aggregometry. Analysis of capillary blood velocity (CBV) and assessment of the presence and absence of RBC aggregates in the nail bed capillaries were performed in vivo using vital digital capillaroscopy (VDC).

Results. RBC aggregation for groups of patients suffering AH and AH+CHD was increased compared to the control group. Thus, in these patients groups, the characteristic aggregation time significantly decreases by an average of (38±13) %. Comparison of the results obtained using in vitro and in vivo methods showed the aggregation index for individuals with high CBV was significantly lower than for individuals with low CBV. The tendency is that the number of aggregates in the capillaries increases with a decrease in CBV.

Conclusion. RBC aggregation is increased in groups of patients suffering AH and AH+CHD compared to the control group. The correlation between parameters measured in vitro and in vivo is evident for patients divided into subgroups according to parameters measured using the VDC. The obtained results allow us to conclude that the used methods are applicable in clinical practice.

Aim. The study aims to evaluate impairment of the rheological and electrical properties of blood, plasma viscosity and blood conductivity in patients with type 2 diabetes mellitus (T2DM) in comparison with the data of the control group of healthy individuals. It also aims to investigate the changes of the skin blood flow responses to cold stress in T2DM patients through wavelet analysis of the peripheral skin temperature pulsations and to estimate their relationships with the blood viscosity and blood conductivity parameters, obtained from the simulation of experimental data with mathematical equations.

Materials and methods. The whole blood viscosity was measured by Contraves LS30 viscometer (Switzerland) at a steady flow in 9 healthy individuals and in 13 patients with type 2 diabetes mellitus. Time variation of whole blood conductivity σ under transient flow at rectangular and trapezium shaped Couette viscometric flow and under electric field of 2 kHz was determined. The amplitudes of the skin temperature pulsations (ASTP) were monitored by «Microtest» device («FM-Diagnostics», Russia). To analyze the temperature fluctuations, wavelet transformation analysis of the low amplitude oscillations of skin temperature in accordance with myogenic (0.05–0.14 Hz), neurogenic (0.02–0.05 Hz), and endothelial (0.0095–0.02 Hz) control mechanisms of the vascular tone (WAST method) was applied.

Results. Blood viscosity was increased in the T2DM patients’ group, while blood conductivity decreased in comparison to controls. Two sigmoidal equations were applied to describe the kinetics of blood conductivity. Both models include conductivity indices (σ₁ , σ₂ , σ₃ ) and time indices too. The Pearson correlations between these parameters and the ASTP in the frequency ranges, corresponding to the myogenic, neurogenic and endothelial mechanisms of the microcirculation tone regulation were analyzed. The correlation analysis revealed good ASTP–(σ₁ , σ₂ , σ₃ ) relationships in the neurogenic range 3 minutes after the cold test, while the ASTP–(σ₁ , σ₂ , σ₃ ) correlation in the myogenic frequency range before the cold test was negative (r<–0.8, p<0.5).

Conclusion. The results complement the studies of the microvascular regulatory mechanisms and endothelial dysfunction in patients with type 2 diabetes mellitus, as well as their relationships with the rheological and electrical properties of blood.

The micromechanical properties of leukocytes make a certain contribution to the blood flow velocity in the microcirculatory bed, while the micromechanical properties themselves change under the influence of a complex network of purinergic signals.

The aim of the work was to study the micromechanical properties and functional activity of granulocytes in normal conditions and in patients with acute lymphoblastic leukemia when simulating exogenous loading with ATP in vitro.

Materials and methods. Leukocytes were isolated from the blood of patients with acute lymphoblastic leukemia and healthy people. Each sample was divided into a test sample and a control sample. In the test samples, the loading with ATP in vitro was simulated. Leukocytes of the control samples were incubated in the culture medium without the addition of ATP. Young’s modulus and adhesion force were measured using an atomic force microscope in the force spectroscopy mode. The cell surface potential was measured in an atomic force microscope in the Kelvin mode. To assess the functional activity of granulocytes, hypoosmotic tests in vitro and determination of migration activity were used.

Results. In tests with exogenous ATP, both in samples from healthy people and from patients with acute lymphoblastic leukemia, a decrease in the rigidity and potential of the plasma membrane surface, an increase in the adhesive properties of leukocytes and migration activity were found. At the same time, the responses of granulocytes to the osmotic loading were different: for example, in the group of healthy people, the loading with ATP caused cell contraction and a decrease in the use of the membrane reserve by the cell in a hypotonic environment, and in patients with acute lymphoblastic leukemia, it caused an increase in the volume and more intensive use of the membrane reserve in volume regulation.

Conclusion. The revealed effects indicate the leading role of the ATP molecule in the signal transduction mechanisms between blood cells in the microvasculature. The increase in the adhesive properties of the cell surface of granulocytes revealed in the study, in parallel with the increase in their migration activity under the influence of the ATP molecule, can contribute to the development of inflammation in the vessel wall.

Relevance. The relevance of the study is determined by the fact that hopes are placed in the cell therapy for patients with critical limb-threatening (CLI) ischemia as a method of the restoration of blood circulation in the affected limb in patients who cannot undergo surgical or endovascular intervention. Aim. To evaluate the efficiency of allogeneic MSCs for the treatment of critical lower limb ischemia (randomized placebo-controlled study).

Materials and methods. The study included 34 patients with critical lower limb ischemia (grade 4 according to Pokrovsky). There were 18 patients in the MSC group, and 16 patients in the placebo group). The groups were comparable concerning age, disease duration, and comorbidities. Allogeneic MSCs (phenotype CD73⁺, CD90⁺, CD105⁺, CD45^–, CD34^–, CD14^–) were injected into the posterior calf muscles. Clinical outcome, ankle pressure, transcutaneous oxygen tension (tcpO₂), and pain-free walking distance (PFWD) were evaluated. The patients were followed-up for 12–36 months. According to the clinical outcome in each group, the patients were divided into subgroups with «effect (+)» or «effect (–)». In 2 patients, there was an «uncertain clinical outcome». When analyzing the results, these patients were assigned to one or another subgroup.

Results. In the MSC and placebo groups, the clinical outcome assessed as «effect (+)» or «effect (–)» did not differ (OR 1.5; 95 % CI 0.34–6.7). With different variants of group formation and with the assignment of patients with an «uncertain clinical outcome» to a one or another subgroup, the final results neither differed. According to instrumental research methods (PFWD, tcpO₂, ankle pressure, angiography), there were no differences in the MSC and placebo groups. Conclusion. With different variants of analysis and group formation, no convincing evidence that allogeneic MSCs can be effective for the treatment of critical lower limb ischemia have been obtained.

Introduction.The study was devoted to assessing the effectiveness of laser therapy in the treatment of spondylogenic radiculoischemias. Low-intensity laser therapy and vaporization technology were used.

Aim – to improve treatment and outcomes in patients with compression of the spinal roots in herniated intervertebral discs using various methods of laser therapy.

Materials and methods. In two groups, the results of treatment of 225 patients with clinical manifestations of spondylogenic lumbosacral radiculoischemias were analyzed using laser therapy techniques. In 115 cases (group 1), laser treatment was performed using the method of puncture polychannel laser disk decompression. In 110 patients (group 2), low-intensity percutaneous laser therapy was used. The dynamics of the clinical and neurological manifestations of the disease was recorded: the time of pain syndrome reduction, the dynamics of motor and sensory disorders of the corresponding root, changes in parameters according to the Roland-Morris and Oswestry Disability questionnaire.

Results. In both groups, an improvement in clinical and neurological manifestations was obtained: the intensity of pain syndrome according to VAS decreased in more than 70 % of the observed individuals. A significant improvement in the parameters of vital activity was revealed according to scales with a long-lasting effect (more than 12 months) with an improvement in the blood supply to the spinal roots.

Conclusion. Laser radiation has significant clinical effectiveness; the important parameters are the wavelength and rate of the radiation. Structural-modifying action and improvement of microcirculation (of arterial and venous bed) are achieved. Evaluation of the effectiveness of polychannel laser puncture decompression is advisable using scales and questionnaires. Low-intensity percutaneous laser therapy and monochannel interstitial laser therapy provide a targeted antiedemic and neuroprotective effect with the possibility of dosing and control. The treatment is highly effective and improves the prognosis of the disease.

Introduction. Percutaneous interventions used in the treatment of acute coronary syndrome (ACS) may be complicated by the recurrence of the ischemia clinical picture due to the late lumen loss of the stent. Factors influencing the risk of the restenosis developing may differ depending on the clinical situation and stent characteristics.

Objective. To identify risk factors for repeated revascularization in patients with ACS without ST-segment elevation after placement of everolimus-eluting stents. Materials and methods. The study included 126 patients with ACS, who received platinum-chromium containing everolimus-eluting stents. The main clinical and laboratory parameters of the patients were analyzed. After 12 months, the combined endpoint (death, myocardial infarction in the basin of the stented artery, repeated revascularization of the stented vessel) was assessed.

Results. During the followup, 18 of 126 patients (14.3 %) reached the combined endpoint. Among patients who reached the endpoint, there were more women (10 (24.4 %) and 8 (9.4 %); p=0.02). In patients who reached the endpoint, the level of highly sensitive troponin was significantly higher (0.032 (0.007; 0.32) ng/ml versus 0.005 (0.002; 0.022) ng/ml; p=0.005), there was a lower left ventricular ejection fraction (52.2±12.3 % vs 58.6±8.9 %; p=0.02) and glomerular filtration rate (68.5±15.7 ml/min vs 76.3±18.2 ml/min; p=0.04), and there was also a significantly lower level of triglycerides (1.3±0.4 mmol/L and 1.8±0.9 mmol/L, p=0.004) and VLDL (0.6±0.2 mmol/L and 0.8±0.4 mmol/L, p=0.006). According to multivariate regression analysis, the leading factors influencing the risk of repeated revascularization were diabetes mellitus (OR 4.25; 95 % CI: 1.12–16.15; p=0.03), glomerular filtration rate and triglyceride level (OR 0.25; 95 % CI: 0.07–0.93; p=0.03).

Conclusions. When using everolimus-eluting stents, diabetes mellitus, decreased glomerular filtration rate and low blood triglyceride levels are among the main factors affecting the risk of in-stent restenosis.

Introduction. Hyperviscosity syndrome plays an important role in the pathogenesis of arterial hypertension and its complications associated with impaired microcirculation in target organs. Therefore, along with the use of antihypertensive drugs, it is important to pay attention to the correction of the hyperviscosity syndrome with means of hemorheological agents.

The aim is to study the effect of metoprolol and its combined use with dihydroquercetin (DHQ) on the rheological parameters of blood in rats with spontaneous arterial hypertension.

Materials and methods. The experiments were carried out on normotensive male Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHRs). SHRs of the experimental groups received metoprolol (50 mg/kg) or metoprolol and DHQ (50 mg/kg each) daily intragastrically for 6 weeks in 1 % starch mucus; SHRs of the control group and normotensive rats received 1 % starch mucus according to the same scheme. Systemic blood pressure was registered in awake animals. Blood was sampled from the catheterized right common carotid artery. Blood viscosity, plasma viscosity, hematocrit, erythrocyte aggregation and deformability were studied.

Results. Compared with the parameters in normotensive rats, SHRs showed significant increase of blood viscosity, hematocrit, erythrocyte aggregation, and decrease of erythrocyte deformability. The course administration of metoprolol induced to a further increase in blood viscosity at low shear rates (15–45 s–¹); plasma viscosity, hematocrit and micro-rheological parameters in rats of this group did not significantly differ from those in the control. With the combined administration of metoprolol and DHQ, blood viscosity at shear rates of 300 and 450 s–¹ and erythrocyte aggregation were significantly lower than in the control SHRs.

Conclusions. The course administration of metoprolol increases the severity of the hyperviscosity syndrome in SHRs. The use of DHQ together with metoprolol partially eliminates adverse effects of the beta blocker on blood rheology parameters.

Objective. Measurement and comparison of the aggregation and disaggregation forces of individual erythrocytes during the formation or breakdown of a paired aggregate in vitro in the blood of patients with type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) using the optical tweezers method. Materials and methods. A total of 50 people were included in the study. Of these, 10 people with T1DM (aged 28±15.8), 26 people with T2DM (aged 66±13). The control group consisted of 14 apparently healthy volunteers (46±21 years old). Measurements of the forces of pair interaction of erythrocytes in a diluted suspension were carried out in vitro by the method of dual-channel optical tweezers. The force of aggregation of erythrocytes FA (pN) and the force of disaggregation FD (pN) were measured and their ratio FD/FA was calculated.

Results. The erythrocyte aggregation forces in the T1DM group did not differ significantly from the control group. However, the forces of disaggregation in the T1DM group were significantly lower than in the control group (p<0,05). The ratio of the forces of disaggregation to the forces of aggregation was lower in the T1DM group compared to the control group (p<0.005). In T2DM group, erythrocyte aggregation forces were higher compared to the control group (p<0.005). At the same time, the ratios of the forces of disaggregation to the forces of aggregation in T1DM group and T2DM group did not differ.

Conclusion. Both T1DM group and T2DM group are characterized by hyperaggregation of erythrocytes. However, given the data obtained, it can be assumed that the mechanisms of such hyperaggregation are different.

Introduction. In physiological research, an important task is to find the relationship between the various functional parameters of the organism, its individual systems and its elements. These relationships can be complex, mediated by additional factors and when using pair correlation, they cannot be detected. In this case, it seems justified to use factor analysis to search for the hidden structure of relationships between many variables. The aim. Factor analysis of a set of data, including indicators of aerobic performance, central hemodynamics, microcirculation (MC) and hemorheology.

Materials and methods. The study involved 172 men aged 20 to 60 years. Physical performance was determined using the PWC170 test. Microcirculation parameters were determined using biomicroscopy and Laser Doppler Imaging (LDI). The complex of hemorheological characteristics included the viscosity of blood and plasma, aggregation and deformability of erythrocytes. Statistical processing, including factor analysis, was carried out using the Statistica 6.0 software package. The factorial model included 32 parameters. When interpreting the results of factor analysis, variables with factor loadings of more than 0.60 were considered.

Results. Three factors were identified, which accounted for 71 % of the total variance. The first factor closely correlated with the level of the body’s aerobic performance parameters and its adaptive potential. The second factor correlated with hemodynamic parameters at the central and microcirculatory level, including integral rheological parameters. The third factor correlated with the parameters of microvessels and the rheological properties of erythrocytes.

Conclusions. The constructed factor model demonstrates the level structure of the relationships of indicators of aerobic performance, central hemodynamics, microcirculation, and hemorheology. The selected factors – the hidden elements of this structure linking individual variables – were interpreted as levels of integration: organismic, systemic and microlevel.

Among the signaling molecules involved in the regulation of intra- and intercellular systems in various types of cells, a special place is occupied by gaseous compounds – gasotransmitters (GTs). Currently, the most studied are three molecules: nitrogen oxide (NO), carbon monoxide (CO) and hydrogen sulfide (H₂S). For them, the enzymatic systems of intracellular synthesis and degradation have been determined, the physiological effect has been proved, and the intracellular mechanisms have been determined. Changes in the work of these mechanisms under the influence of GTs causes the development of physiological and/or pathophysiological reactions. These GTs are involved in the regulation of various organs and systems of the human body under normal and pathological conditions, including the structure and function of the circulatory system. In this article, special attention is paid to the influence of all three GTs and their donors on the vascular and hemorheological aspect of the work of blood circulation, and especially on an underdeveloped problem – the microrheology of erythrocytes. It has been shown that all three GTs, along with the well-known vasodilating effect, reduce the adhesion and aggregation of platelets and leukocytes, as well as moderately stimulate the deformability of erythrocytes and strongly inhibit their aggregation. The performed analysis of the data indicates that, along with the specific signaling cascades for each GT, the use of a common signaling pathway associated with soluble guanylate cyclase and NO synthase was also revealed in microrheological responses. The intersection of signaling pathways triggered by NO, CO and H₂S on common effectors, as well as their interaction with each other (cross-talk), can determine the final, resulting functional response of the cell.