Integral and Local Methods for the Evaluation of the Hemostasiological Profile in Sheep at Various Stages of Implantation of a Biodegradable Vascular Graft.

The aim of this study was to evaluate the efficiency of local and integral methods of the assessment of the hemostasiological profile in sheep at various stages of implantation of a biodegradable vascular graft. Materials and Methods: The object of the study was the whole blood of sheep collected at the stage of premedication, during the intraoperative period, and in the early postoperative period. Thromboelastography was used to assess the kinetics of clot formation and changes in its viscoelastic properties in whole blood samples. The thrombin generation test was performed in platelet-rich plasma (PRP) and platelet-poor plasma (PPP) with the assessment of quantitative and temporal parameters. The platelet factor 4 concentration in PRP and PPP was measured by the enzyme immunoassay. The functional activity of platelets in PPP was assessed with inductors and without additional stimulation. Prothrombin complex activity, APTT values, thrombin time, fibrinogen concentration, antithrombin III and protein C activity, soluble fibrin monomer complexes, and fibrinolysis were determined in blood plasma. Results: Multidirectional changes in the hemostasiological profile at various stages of vascular prosthesis implantation have been revealed. On the one hand, it is an increased prothrombogenic status, on the other hand, it is the development of hypocoagulation. Shortening of the R (blood coagulation time) and K (clot formation time) intervals and an increase in the angle parameter and maximum amplitude on the thromboelastogram in all the studied periods relative to the reference values, a significant increase in platelet factor 4 in PRP and increased platelet aggregation testified in favor of hypercoagulation. However, the quantitative parameters of the thrombin generation test and a number of coagulogram indicators pointed to hypocoagulation in the intraoperative and early postoperative periods. Conclusion: The comparative analysis of local tests characterizing the state of hemostasis and indicators of integral methods demonstrated the advantages of the latter in assessing thrombotic risks during implantation of vascular grafts. Local tests are not sufficient to assess the dynamics of the coagulation process in real time and are not always sensitive to hypercoagulation. The use of integral methods will help to fill these gaps, make a timely diagnosis of hypercoagulability and minimize the risks associated with the implantation of vascular grafts in future.

Cardiometabolic Effects of Empagliflozin in Patients Undergoing Elective Percu-taneous Coronary Intervention for Type 2 Diabetes Mellitus.

Aim      To evaluate cardiometabolic effects of empagliflozin in patients with ischemic heart disease and type 2 diabetes mellitus (DM) following elective percutaneous coronary intervention (PCI).Materials and methods Patients meeting the inclusion/non-inclusion criteria were randomized into two groups of equal number using simple randomization with successively assigned numbers. Group 1 included 37 patients (18 men and 19 women) who gave their consent for the treatment with empagliflozin 10 mg/day in addition to their previous hypoglycemic therapy. The drug administration started one month prior to the elective PCI and continued for the next 11 months (treatment duration, 12 months). Group 2 (comparison group) consisted of age- and DM duration-matched patients (37 patients; 18 men and 19 women) who continued on their hypoglycemic therapy previously prescribed by endocrinologists during the entire study period. Before the study, 36.11 % patients of the empagliflozin group and 27.03 % of the comparison group had unsatisfactory glycemic control as shown by the level of glycated hemoglobin (HbA1c).Results At 6 and 12 months of the study, fasting glycemia and HbA1c were significantly lower in the empagliflozin treatment group. The groups were comparable by the incidence of adverse outcomes: 8 (22.24 %) patients in the empagliflozin group and 10 (27.04 %) patients in the comparison group (р=0.787). The 12-month empagliflozin treatment reduced total cholesterol (C) by 5.56 % (p<0.05), low density lipoprotein (LDL) C by 3.67 % (p<0.05), visceral adipose tissue area (VATA) by 5.83 % (p<0.05), and subcutaneous adipose tissue area (SATA) by 3.54 % (p<0.05).Conclusion      The empagliflozin treatment for 30 days prior to and after elective PCI can enhance the effectiveness of myocardial revascularization due to the demonstrated beneficial cardiometabolic effects.

Comparative Analysis of the Hemostasiological Profile in Sheep and Patients with Cardiovascular Pathology as the Basis for Predicting Thrombotic Risks During Preclinical Tests of Vascular Prostheses.

The aim of the investigation was to study the details of hemostasiological profile in sheep and patients with coronary heart disease (CHD) and to find the possibility of predicting thrombotic risks during preclinical tests of vascular prostheses on a large laboratory animal model. Materials and Methods: The functional activity of platelets was measured in platelet-rich plasma with inductors: ADP, epinephrine, collagen. Prothrombin activity, international normalized ratio, activated partial thromboplastin time (APTT), thrombin time, fibrinogen concentration, antithrombin III and protein C activity, fibrinolysis were determined in blood plasma. Changes in clot formation and viscoelastic properties of clots were assessed using thromboelastography. Results: Significant differences were found in the hemostasiological profile of sheep and CHD patients. Sheep platelets had increased response to ADP induction and practically no response to epinephrine induction; collagen-induced aggregation was comparable in the study groups. Coagulation hemostasis of sheep was characterized by increased activity of the prothrombin complex, shortened thrombin time, while APTT and fibrinogen values remained comparable. At the same time, sheep exhibited a significant decrease in the activity of anticoagulant and fibrinolytic systems as compared to CHD patients. When assessing dynamic changes in clot formation, it was observed that initiation phase was faster in animals, while clot density exceeded that in patients. Conclusion: The hemostasiological profile of sheep is characterized by the increased speed of thrombus formation, greater strength of the formed clot, and lower lysis ability as compared to CHD patients. The revealed details of the hemostasiological profile of sheep can be potential targets for therapy with antithrombotic drugs that minimize thrombotic risks in preclinical testing of vascular prostheses.

[Relationship of visceral obesity and coronary calcinosis in ischemic heart disease].

AIM: To assess the relationship between the prevalence of visceral obesity (VO) and the severity of coronary calcification (CC) in patients with verified coronary artery disease (CAD). MATERIALS AND METHODS: 125 patients with CAD were examined. Assessment of the morphometric characteristics of visceral adipose tissue (VAT) and CC was perform using multislice computed tomography (MSCT). The calcium index (CI) of the coronary arteries (CA) was determine by the Agatston method. Statistical analysis was perform using Statistica 10.0. RESULTS: VO was detect in 82 (65.6%) patients with CAD. In the presence of VO, higher CC values were observed in the projection of the envelope (p=0.00014), right coronary (p=0.00002) arteries, total CI (p=0.0003), and the prevalence of massive CC. Correlation analysis showed the relationship between the area of VAT and the CC of all the studied localizations. According to the ROC analysis, VO is a significant predictor of massive CC (area under the ROC curve AUC 0.72, 95% CI 0.560.89), in contrast to body mass index BMI (AUC 0.56, 95% CI 0.310.82). CONCLUSION: The index of the ratio of VAT to subcutaneous adipose tissue (VAT/SAT), but not BMI, had a direct correlation with CC. Morphology of VAT may be a significant diagnostic sign of massive CC in patients with CAD, as a factor affecting treatment and prognosis.

The relationship of the epicardial fat and adipo-fibrokines in myocardial infarction.

Analysis of the relationship between the epicardial fat with adipokine and system ST2/IL-33 in-hospital period, and also with the extent of fibrosis of the atrial myocardium through the year after myocardial infarction in patients with visceral obesity. Examined 88 patients with myocardial infarction (MI). Visceral obesity (VO) is established by computed tomography. In fact the presence VO the patients divided into two groups. Determined the concentration of leptin, adiponectin, stimulating growth factor (ST-2) and interlekin-33 (IL-33) in serum on 1st, 12-day in-hospital period and 1 year after MI. Thickness epicardial adipose tissue (EAT) and the percentage of cardiovirus of the myocardium was measured by the method MRI, respectively, on the 12th day of hospitalization and a year after MI. The control group consisted of 30 people. Statistical analysis of data was performed using nonparametric tests. Patients with MI is associated with an increase in the thickness of EAT, imbalance of adipokines with increased leptin, decreased adiponectin in early in-hospital period and development of cardiovirus. Higher values of IL-33 and ЅT2 in the early in-hospital period MI patients with no accompanied by a lower prevalence of cardiovirus in the post-hospital period. The thickness of epicardial fat is directly dependent on the prevalence of myocardial fibrosis, the concentrations of IL-33 and in inverse proportion to the concentration of ЅT2. The degree of cardiovirus is in inverse proportion to the concentration of IL-33 and directly dependent on the concentration of ST2. The increase in EAT closely linked to the development of fibrosis of the atrial myocardium after year. The thickness of EAT more patients MI, which is most pronounced imbalance of adipokines. The metabolic activity of EAT correlated with increased IL-33 and ST2 decrease.

[MicroRNA and obesity. A modern view of the problem (review of literature).] / МикроРНК и ожирение. Современный взгляд на проблему (обзор литературы).

The incidence of obesity is steadily increasing worldwide, reaching the epidemic. Obesity is associated with cardiometabolic diseases through the complex interactions between genetics and epigenetics predisposition, the environment, diet, and lifestyle. However, the molecular mechanisms and factors influencing these processes are not fully known. MicroRNAs are a new class of important regulatory determinants in many biological and pathological processes. There is increasing evidence of the role of miRNAs in the regulation of the functional activity of adipose tissue and the development of obesity. A change in the expression of MicroRNAs can lead to changes in the activity of genes that control a number of biological processes, including inflammation, lipid metabolism, and adipogenesis. Understanding the role of miRNAs in the regulation of adipogenesis and the development of obesity will establish therapeutic targets for the development of new and effective drugs, which will lead to a breakthrough in the fight against obesity and related diseases. This review presents current data on the role of miRNAs in the regulation of the functional activity of adipose tissue, including adipogenesis of white, beige and brown adipocytes, as well as the prerequisites for using miRNAs as biomarkers of obesity and the possibility of therapeutic use.

[Effect of empagliflosin on renal filtration in patients with coronary heart disease undergoing percutaneous coronary intervention].

Aim To evaluate the effect of empagliflozin on glycemia and renal filtration function in patients with stable ischemic heart disease (IHD) and type 2 diabetes mellitus (DM2) who underwent a percutaneous coronary intervention (PCI).Materials and methods This study included 40 patients with stable IHD and DM2 (age, 63 (58; 65) years; DM2 duration, 7 (4; 15) years) who had indications for an elective PCI. At baseline in the total sample, the level of glycated hemoglobin was 7.2 (6.5; 8.3)%; 48.7 % failed to achieve glycemic goals. A decrease in glomerular filtration rate (GFR) to below 60 ml/min/1.73 m2 was observed in 10.3 % of patients. All patients were divided into two group by simple randomization with successively assigned numbers. The main group consisted of 20 patients who received empagliflozin 10 mg/day in addition to their previous hypoglycemic therapy irrespective of their baseline glycemic control. Patients of the comparison group (n=20) continued on their previous hypoglycemic therapy as prescribed by their endocrinologist. The follow-up duration was 6 months. Statistical analysis was performed with the Statistica 10.0 software.Results The empagliflozin treatment improved the glycemic control; in the comparison group, no significant changes in glycemic control were observed. In both groups, GFR significantly decreased during the follow-up period; median decreases in GFR were -6.0 (-16.0; 4.0) and -8.4 (-26.5; 2.5) ml/min / 1.73 m2 in the main and comparison groups, respectively (p = 0.646). No significant changes in 24-h proteinuria were observed for patients taking empagliflozin. In the control group, the 24-h urinary protein excretion significantly progressed (p=0.011) during the follow-up period.Conclusion In patients with DM2 and stable IHD who underwent a PCI, addition of empagliflozin 10 mg/day to their current hypoglycemic therapy was associated with a significant improvement of glycemic control. The decrease in GFR during the empagliflozin treatment did not significantly differ from the value for patient receiving the other hypoglycemic therapy.

[Dynamics of Parameters of Transmitral Blood Flow and Markers of Myocardial Fibrosis in Patients with Myocardial Infarction].

Aim      To study possible correlations between echocardiography (EchoCG) indexes and markers of myocardial fibrosis, procollagen I C-terminal propeptide (PICP) and procollagen III N-terminal propeptide (PIIINP) during one year following ST-segment elevation myocardial infarction (STEMI).Material and methods  120 patients with STEMI were evaluated. EchoCG was used to assess dimensions and volumes of heart chambers, left ventricular (LV) systolic function, mean pulmonary arterial pressure (mPAP), and indexes of LV diastolic function (Em, early diastolic lateral mitral annular velocity; e', peak early diastolic septal mitral annular velocity; E / e', ratio of peak early diastolic transmitral inflow velocity and mitral annular velocity  -, Е / А, ratio of peak early and late transmitral inflow velocities; DT, deceleration time of LV early diastolic filling). EchoCG indexes and serum concentrations of PICP and PIIINP were determined at 1 (point 1) and 12 (point 2) days of disease and one year after STEMI (point 3). The sample was divided into two groups: group 1 (n=86; 71.7 %) included patients with a LV ejection fraction (EF) ≥50 % and group 2 (n=34; 28.3 %) consisted of patients with LV EF ≤49 %.Results At one year, the number of patients with signs of diastolic dysfunction increased by 10% in group 1 whereas myocardial systolic dysfunction worsened in both groups. LV EF decreased in 15 (17.4%) patients of group 1 and in 4 (11.8%) patients of group 2. Concentrations of PIIINP were correlated with Em, E / e', mPAP, PICP, e', and LV EF.Conclusion      Direct correlations between PIIINP concentrations and Em, E / e', and mPAP were found in the group with LV EF ≥50 %. In the group with LV EF <50 %, correlations were observed between PICP concentrations, LV EF, and e'. Also, in this group, the increase in PIIINP was statistically more significant. These results indicate continuing formation of myocardial fibrosis in a year following MI, which may underlie progression of chronic heart failure.

[Adiponectin gene expression in local fat depots in patients with coronary heart disease depending on the degree of coronary lesion].

AIM: To determine the dependence of adiponectin gene expression by subcutaneous, epicardial and perivascular adipocytes on the degree of coronary lesion in coronary heart disease. MATERIALS AND METHODS: 84 patients with coronary artery disease were examined. Of these, 39 people showed a moderate degree of atherosclerotic lesion of the coronary bed (less than or equal to 22 points) on the SYNTAX Score scale, 20 severe (2231 points), and 25 extremely severe (more than 32 points). Upon admission to the hospital, all patients underwent an echocardiographic study (Echocardiography, Acuson, Germany) with the calculation of the ejection fraction (EF) of the left ventricle (LV) to assess its systolic function. During a planned surgical intervention (coronary bypass surgery, CABG), adipocytes of subcutaneous, epicardial (EAT) and perivascular adipose tissue (PVAT) were taken. Adiponectin gene expression was evaluated by polymerase chain reaction (real-time PCR) using TaqMan probes. Statistical analysis was performed using Statistica 9.0. RESULTS: The maximum level of adiponectin expression was detected in adipocytes of PVAT, and the minimum EAT. With an increase in the degree of atherosclerotic lesion of the coronary bed, the expression of the adiponectin gene in adipocytes of local depots significantly decreases r=-0.82; p=0.023. Moreover, the low level of gene expression in EAT correlated with a decrease in LV EF by r=0.73; p=0.03. In adipocytes of subcutaneous and especially PVAT, gene expression was the highest in patients with a moderate degree of coronary lesion. CONCLUSIONS: Low adiponectin gene expression in EAT is associated with an increase in the degree of atherosclerotic lesion of the coronary bed and a decrease in LV EF.

[Ceramids and their role in the development of cardiovascular diseases (review of literature).]

Almost all known stress stimuli, including inflammatory agonists, chemotherapeutic agents and saturated fatty acids, cause the synthesis of ceramide and its metabolites. In recent studies, it has been shown that excessive synthesis of ceramides causes the development of various metabolic diseases, such as obesity, diabetes and cardiovascular diseases. Currently, the role of cеramids in the development of obesity and diabetes has been studied quite well. At the same time, studies devoted to the study of lipid data in the development of cardiovascular disease are not large. In this review, we generalize the data on this new class of bioactive lipids for understanding their role in the development of cardiovascular diseases.

[Expression of gene and content of adiponectin in fatty tissue in patients with ischemic heart disease]. / Ékspressiia gena i soderzhanie adiponektina v zhirovoi tkani u patsientov s ishemicheskoi bolezn'iu serdtsa.

The purpose of the study was to investigate the features of expression and adiponectin content in the adipocyte culture of subcutaneous, epicardial, and perivascular adipose tissue and the effect of various doses of rosuvastatin on these processes. 29 patients with coronary artery disease were examined. Adipocytes were isolated from the samples of SAT, EAT and PVAT which were taken during coronary artery bypass surgery, followed by cultivation in the presence of rosuvastatin and evaluation of gene expression and adiponectin concentration. Adipocytes SAT, EAT and PVAT differed in the level of adiponectin secretion and expression of its gene. On day 1 of cultivation the expression of the adiponectin gene in the EAT was 2.3 times lower than in the PVAT. On day 2 of cultivation the expression of the adiponectin gene was reduced both in the EAT and the PVAT as compared to the SAT. When rosuvastatin was added at a concentration of 1 mmol/L, adiponectin gene expression in PVAT was higher than when rosuvastatin was added at a concentration of 5 mmol/L, in the adipocyte culture of SAT effect was opposite. Thus, the adipocytes of EZhT and, to a greater extent, PAS, can be a therapeutic target for statins in the case of the pathological activation of adipose tissue.

The marker of adverse prognosis 1.5-anhydroglucitol in patients with coronary heart disease in the long-term period after planned myocardial revascularization.

AIM: Determination of the prognostic value of 1.5-anhydroglucitol (1.5-AG) for the development of cardiovascular events in patients with coronary heart disease (CHD) within a year after a planned percutaneous coronary intervention (PCI). MATERIALS AND METHODS: A prospective study was conducted in Federal State Budgetary Institution Research Institute for Complex Issues of Cardiovascular Disease among 149 patients admitted to planned PCI in the period from 2016 to 2017. Criteria for inclusion in the study: age up to 70 years, angina I-IV functional classes or post-infarction cardiosclerosis, the presence of indications for planned PCI. -Exclusion criteria from the study: previous myocardial revascularization; prosthetic heart valves; decompensation of chronic heart failure, anemia of any degree; acute coronary syndrome in index hospitalization; exacerbation of somatic diseases. The results of the research were processed by Statistica Windows 6.0. RESULTS: During the year after planned PCI, 39 (26.14%) cardiovascular events were registered in patients with CHD, of whom more than half of the cases (51.28%) were associated with the presence of indications for PCI of de novo. Lower levels of 1.5-AG were observed in the group of patients with cardiovascular events (p=0.000). When patients were divided according to median of the studied marker patients with a concentration of 1.5-AG less 20.96 µg/ml (before PCI) were more likely to have PCI after restenosis of the stent, compared with patients whose median concentration of this marker was higher (p=0.028). The logistic regression method revealed a significant direct relationship reflecting the prognostic value of lower concentration of 1.5-AG in relation to the development of cardiovascular events in patients regardless of the presence of carbohydrate metabolism disorders [OR 0.25 (0.10-0.62)]. CONCLUSION: According to the results of the study, the prognostic value of the concentration of 1.5-AG less 20.96 µg/ml was established in relation to the development of cardiovascular events in patients with CHD during the year after a planned PCI, regardless of the presence of carbohydrate metabolism disorders.

The role of perivascular adipose tissue in the development of cardiovascular diseases. The importance of diagnosis for assessing the risk stratification of cardiovascular diseases.

Obesity is closely associated with metabolic and cardiovascular diseases, including dyslipidemia, coronary artery disease, hypertension, and heart failure. Adipose tissue (AT) is identified as a complex endocrine organ, with a wide range of regulatory functions at the cellular, tissue and systemic levels. Various terms, including paracardiac, epicardial and pericardial, are used to describe the fatty deposits surrounding the heart. Among all the fat depots, perivascular AT (PVAT) is of great biological significance for the cardiovascular system due to its anatomical proximity to the vessels. Recent studies have shown the presence of a complex, bidirectional paracrine and vasocardial signaling system between the vascular wall and PVAT. In the review, we will discuss the biological role of PVAT in both the physiological state and cardiovascular pathology, emphasizing its dual proatherogenic and antiatherogenic role. Let us consider PVAT as a target for various therapeutic agents in cardiovascular diseases. We will also analyze data on the role of non-invasive techniques as a diagnostic tool for assessing coronary artery inflammation.

[Ghrelin Physiology and Pathophysiology: Focus on the Cardiovascular System].

Ghrelin is a multifunctional peptide hormone, mainly synthesized by P / D1 cells of the stomach fundus mucosa. Its basic effect, which is realized via GHS-R1 α receptor in the arcuate and the ventromedial nucleuses of hypothalamus, is stimulation of the synthesis of pituitary hormones. Ghrelin is involved in control of appetite and energy balance, regulation of carbohydrate and lipid metabolism, cell proliferation and apoptosis, as well as modulation of functioning of gastrointestinal, cardiovascular, pulmonary and immune systems. It was found that cardiomyocytes are able to synthesize ghrelin. High concentrations of GHS-R1α in the heart and major blood vessels evidence for its possible participation in functioning of cardiovascular system. Ghrelin inhibits apoptosis of cardiomyocytes and endothelial cells, and improves the functioning of the left ventricle (LV) after injury of ischemia-reperfusion mechanism. In rats with heart failure (HF) ghrelin improves LV function and attenuates development of cardiac cachexia. In addition, ghrelin exerts vasodilatory effects in humans, improves cardiac function and reduces peripheral vascular resistance in patients with chronic HF. The review contains of the predictive value of ghrelin in the development and prevention of cardiovascular disease.

[Polyvascular disease in patients with myocardial infarction and chronic kidney disease].

AIM: To study polyvascular disease in patients with myocardial infarction (MI) and chronic kidney disease (CKD). MATERIALS AND METHODS: A total of 954 patients older than 18 years old with ST-segment elevation MI (STEMI) up to 24 hours of pain onset were included in the study. Clinical and demographic data were collected for all patients, including physical examination, 16-lead electrocardiogram recording, echocardiography, laboratory assessment with the measurements of cardiospecific enzymes and serum creatinine. Glomerular filtration rate (GFR) was estimated according to the CKD-EPI equation. Of them, 771 (81%) underwent coronary angiography, duplex scanning of the brachiocephalic (BCA) and lower extremity arteries (LEA). Patients with stage 1-4 CKD diagnosed according to the criteria provided by the Russian Society of Nephrologists were allocated into a separate group (n=281; 36.5%). CKD stages were determined with the level of GFR. Patients with stage 5 CKD were excluded from the study. Renal dysfunction was defined as the presence of an estimated GFR less than 60 ml/min/1.73 m2. RESULTS AND DISCUSSION: The results of the study indicate a high prevalence of PolyVD in patients with CKD. Every second patient had LEA stenosis (p.

[The association of biological markers with echocardiographic indices in patients with myocardial infarction with ST segment elevation and preserved left ventricular ejection fraction].

AIM: To compare dynamics of biological marker concentrations with echocardiographic data in patients with ST elevation myocardial infarction (STEMI) and preserved LV function during the hospitalization period. MATERIALS AND METHODS: The study successively included 100 patients with diagnosis of STEMI and LV ejection fraction.

Influence of visceral obesity on the secretion of adipokines with epicardial adipocytes in patients with coronary heart disease.

AIM: To study adipokine-cytokine profile of epicardial adipocytes (EAT) and subcutaneous adipose tissue (SAT) in conjunction with the area of visceral adipose tissue (VAT), biochemical and clinical characteristics of patients with coronary heart disease. MATERIALS AND METHODS: Examined 84 patients (70 men and 14 women) with coronary artery disease. In fact the presence of visceral obesity (VO) the patients were divided into two groups. Patients VO the sampling of adipocytes of EAT and SAT, with subsequent cultivation and evaluation of adipokine and provospalitelna activity. Carried out the determination of carbohydrate and lipid metabolism, adipokine and pro-inflammatory status in the blood serum. RESULTS: It was found that adipokine-cytokine profile of adipocytes of EAT and SAT differ. Adipocytes art of the disease on the background characterized by an increase IL-1, TNF-α, leptin-adiponectin relationships and a decrease in the content of protective factors: adiponectin and anti-inflammatory cytokine IL-10. While the SAT adipocytes was characterized by a decrease in the concentration of soluble receptor for leptin and the more pronounced leptinresistance, and the increase in proinflammatory cytokines was offset by the increase in the concentration of IL-10. The presence associated with multi-vessel coronary bed lesion, multifocal atherosclerosis, insulin resistance, atherogenic dyslipidemia, an imbalance of adipokines and markers of inflammation. So the value of the square VAT determined higher concentrations of leptin, TNF-α in adipocytes and serum, lipid and carbohydrate metabolism and a lower content of soluble receptor for leptin. CONCLUSION: Thus, the disease on the background of the status of the adipocytes of EAT characterized as a "metabolic inflammation", and may indicate the direct involvement of adipocytes in the pathogenesis of coronary artery disease, due to the formation of adipokine imbalance and the activation of proinflammatory reactions.

[The perspectives of application of retinol-binding protein as a biomarker of risk of cardiovascular pathology.]

The fatty tissue is an endocrine organ secreting biologically active factors called adipokines that have systemic and local features. The adipokines play an important role in development of complications caused by obesity. nowadays, retinol-binding protein 4 (RBP4), one of adipokines identified recently, is considered as a connecting link between obesity and its complications. Adipokine participates in development of resistance to insulin and correlated with cardio-metabolic markers at chronic inflammatory diseases, including diabetes mellitus type II, metabolic syndrome and cardio-vascular diseases. It is considered that inflammation, produced by RBP4, induces resistance to insulin and cardio-vascular diseases. It seems that RBP4 is an adipokine that both induces resistance to insulin and participates in pathogenesis of other metabolic complications of obesity. This is confirmed by a tight relationship between RBP4 and atherogenic lipoproteins, atherosclerotic affection of vessels and cardio-vascular diseases. However, an important restriction in certain studies related to RBP4 is that they included patients who received medicinal therapy (sugar lowering and hypo-lipidemic pharmaceuticals) or had renal and hepatic insufficiency. The mentioned factors impact concentration of RBP4 in blood and hence can distort the results. In spite of that, the established potential metabolic role of RBP4 requires a further investigation. Besides further carefully planned studies are required focusing on establishing is RBP4 a molecular participator of molecular alterations or it is only a dynamically volatile "witness". The present review summarizes actual knowledge concerning the role of RBP4 under obesity, in development of dyslipidemia, insulin resistance and cardio-vascular diseases. The purpose of the study is to summarize data of studying of inflammatory and immune effects of RBP4 especially in case of cardio-vascular diseases and also establishment of perspective of applying retinol-binding protein as a potential biomarker of cardiovascular risk.

Adipokine and Cytokine Profiles of Epicardial and Subcutaneous Adipose Tissue in Patients with Coronary Heart Disease.

The content of adipokines, pro- and anti-inflammatory cytokines were studied in adipocytes isolated from epicardial and subcutaneous adipose tissue of 24 coronary heart disease patients. The content of leptin and soluble leptin receptor in adipocytes of epicardial adipose tissue was higher by 28.6 and 56.9% and the level of adiponectin was lower by 33% than in adipocytes of the subcutaneous fat. In culture of epicardial adipocytes, the levels of proinflammatory cytokines TNF-α and IL-1 were higher. Subcutaneous adipose tissue adipocytes were characterized by higher levels of anti-inflammatory cytokines IL-10 and FGF-ß. In epicardial adipocytes of coronary heart disease patients, the concentrations of leptin, TNF-α, and IL-1 were higher, while the levels of defense regulatory molecules (adiponectin, IL-10, and FGF-ß) were lower than in subcutaneous adipocytes.

[THE ROLE OF LOW-FREQUENCY PIEZOTHROMBOELASTOGRAPHY IN THE COMPREHENSIVE EVALUATION OF HEMOSTASIS IN CORONARY BYPASS SURGERY WITH CARDIOPULMONARY BYPASS].

Aim: To monitor the hemostatic system during platelet concentrate transfusions using low-frequency piezothromboelastography in patients with coronary bypass surgery given aspirin therapy. Materials and Methods: The study involved 148 patients with coronary bypass surgery, with 76 ones undergoing intraoperative transfusion of platelet concentrate and 72 treated without transfusion. The control group consisted of 20 healthy individuals. In the perioperative period indicators of vascular-platelet, coagulation, anticoagulant and fibrinolytic components of hemostasis were evaluated by low-frequency pezotromboelastography using the ARP-01M "Mednord" hardware and software system (Russia). Results: It was shown that the antiplatelet effect of aspirin in the preoperative period was manifest as inhibition of the initial stage of blood coagulation accompanied by increased thrombin potential, the total gain of anticoagulant and fibrinolytic activity of the blood. Heart-lung bypass was accompanied by structural and chronometric anticoagulation, reduction of anticoagulation and increase of blood fibrinolytic activity. In the postoperative period, structural and chronometric anticoagulation was more pronounced in patients who did not undergo transfusion of platelet concentrate than in the group of patients with transfusion. Donor platelets further increased the blood hemostatic potential by neutralizing the antiplatelet effect of aspirin. Perioperative thrombohemorrhagic complications were absent in both groups. Conclusion: Low-frequency piezothromboelastography provides a tool for real-time monitoring the functional state of hemostasis system. Transfusion of platelet concentrate is not advisable given that the thrombin potential is preserved as confirmed by the results of low-frequency piezothromboelastography.