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Background. In the pathogenesis of ischemic cardiomyopathy (ICMP), angiopoiesis remains unexplored.The aim. To describe the vasculature of the heart and the imbalance of angiogenesis mediators in the coronary circulation in association with the number of endothelial progenitor cells (EPC) and desquamated endothelial cells (DEC) in the blood of patients with coronary heart disease (CHD), suffering and not suffering from ICMP.Methods. Fifty-two patients with CHD (30 patients with ICMP, 22 patients without ICMP), 15 healthy donors were examined. The content of EPC (CD14+CD34+VEGFR2+) in the blood from the cubital vein and DEC (CD45–CD146+) in the blood from the coronary sinus and the cubital vein was determined by flow cytometry. The concentrations of VEGF-A (vascular endothelial growth factor A), PDGF (platelet-derived growth factor), and SDF-1 (stromal cell-derived factor 1) in blood plasma were recorded using immunofluorescence assay; the angiopoietin-2, MMP-9 (matrix metallopeptidase 9) were recorded using enzyme immunoassay. In myocardial biopsies the specific area of vessels and the expression of αSMA (smooth muscle alpha-actin) were determined by morphometric and immunohistochemical methods.Results. In the peripheral blood of patients with CHD, regardless of the presence of ICMP, the DEC content exceeded the physiological level, and the VEGF-A, PDGF, angiopoietin-2, and MMP-9 corresponded to the norm. In CHD patients without cardiomyopathy, there was an excess of SDF-1 and EPC in the blood from the cubital vein, and in ICMP, their physiological significance was noted. In the coronary blood flow in patients with CHD without cardiomyopathy, an increase in the concentration of PDGF was found, which was not determined in patients with ICMP, who had an increased content of DEC, angiopoietin-2 and MMP-9. The specific area of the vessels in the patients of the two groups was comparable; the expression of αSMA in ICMP was 6.2 times lower than in patients with CHD without cardiomyopathy.Conclusion. The development of ICMP is accompanied by impaired maturation of vessels in the myocardium, associated with the absence of a compensatory reaction of activation of cellular and humoral factors of angiogenesis.

Aim. To identify disturbances of differentiation and subpopulation composition of VEGFR2+ cells in the blood and bone marrow associated with the features of the cytokine profile in the blood and bone marrow in patients with coronary artery disease (CAD) with and without ischemic cardiomyopathy (ICM).Materials and methods. The study included 74 patients with СAD with and without ICM (30 and 44 people, respectively) and 18 healthy donors. In all patients with СAD, peripheral blood sampling was performed immediately before coronary artery bypass grafting, and bone marrow samples were taken during the surgery via a sternal incision. In the healthy donors, only peripheral blood sampling was performed. In the bone marrow and blood samples, the number of VEGFR2+ cells (CD14+VEGFR2+ cells) and their immunophenotypes CD14++CD16-VEGFR2+, CD14++CD16+VEGFR2+, CD14+CD16++VEGFR2+, and CD14+CD16-VEGFR2+ was determined by flow cytometry. Using enzyme-linked immunosorbent assay, the levels of VЕGF-А, TNFα, M-CSF, and IL-13, as well as the content of MCP-1 (only in the blood) and the M-CSF / IL-13 ratio (only in the bone marrow) were determined.Results. The content of CD14+VEGFR2+ cells in the blood of CAD patients with and without ICM was higher than normal values due to the greater number of CD14++CD16-VEGFR2+, CD14++CD16+VEGFR2+, and CD14+CD16++VEGFR2+. In the bone marrow of the patients with ICM, the content of CD14++CD16-VEGFR2+, CD14+CD16++VEGFR2+, and CD14+CD16-VEGFR2+ was lower than in patients with CAD without ICM, and the number of CD14++CD16+VEGFR2+ cells corresponded to that in the controls. Regardless of the presence of ICM in CAD, a high concentration of TNFα and normal levels of VEGF-A and IL-13 were observed in the blood. In CAD without ICM, an excess of MCP-1 and deficiency of M-CSF were revealed in the blood. In the bone marrow, the levels of VEGF-A, TNFα, M-CSF, and IL-13 were comparable between the groups of patients against the background of a decrease in the M-CSF / IL-13 ratio in the patients with ICM.Conclusion. Unlike CAD without cardiomyopathy, in ICM, no excess of VEGFR2+ cells and MCP-1 in the blood is observed, which hinders active migration of CD14+CD16++VEGFR2+ cells from the myeloid tissue, and a decrease in the M-CSF / IL-13 ratio in the bone marrow disrupts differentiation of other forms of VEGFR2+ cells, preventing vascular repair.

Coronary artery disease (CAD) is widely considered a chronic inflammatory disorder, and dysfunction of epicardial adipose tissue could be an important source of the inflammation. Amino-terminal fragment of pro-B-type natriuretic peptide (NT-proBNP) is a known marker of cardiovascular disorders of cardiac origin. Recent studies show that inflammatory stimuli may influence its secretion. Our purpose was to evaluate NT-proBNP serum concentration in relation to immune cell ratios in epicardial adipose tissue (EAT), and cytokine levels in the patients with stable CAD. Patients with stable CAD and heart failure classified into classes II–III, according to the New York Heart Association (NYHA) scale, scheduled for the coronary artery bypass graft (CABG) surgery, were recruited into the study (n = 10; 59.5 (53.0-65.0) y. o.; 50% males). The EAT and subcutaneous adipose tissue (SAT) specimens were harvested in the course of CABG surgery. Immunostaining with anti-CD68, anti-CD45, antiIL-1β and anti-TNFα monoclonal antibodies was performed to evaluate cell composition by differential counts per ten fields (400 magnification). Fasting venous blood was obtained from patients before CABG. Blood was centrifuged at 1500g, aliquots were collected and stored frozen at -40 °С until final analysis. Concentrations of NT-proBNP, IL-1β, IL-6, IL-10, TNFα were determined in serum samples by enzyme-linked immunosorbent assay (ELISA). We have found increased production of IL-1β and TNFα cytokines in EAT compared to SAT. Concentrations of NT-proBNP exceeded 125 pg/ml in 4 patients, and correlations between the CD68+ macrophage counts in both EAT and SAT samples (rs = 0.762; p = 0.010 and rs = 0.835; p = 0.003, respectively). NT-proBNP levels showed positive relations with CD45+ leukocyte counts (rs = 0.799; p = 0.006), and with IL-1β+ cell numbers (rs = 0.705; p = 0.023) in EAT samples only. As for the serum biomarkers, NT-proBNP levels showed negative correlation with fasting glucose levels (rs = -0.684; p = 0.029), and positive correlation with serum IL-6 concentrations (rs = 0.891; p = 0.001). Increased serum concentrations of NT-proBNP in CAD patients correlate with accumulation of macrophages in EAT, which is associated with increased production of IL-1β in EAT and correlates with some metabolic parameters.

Background. The attention of many researchers is focused on studying the role of adipokines secreted by subcutaneous, visceral, epicardial, and perivascular adipose tissues in the pathogenesis of diseases of the cardiovascular system. At the same time, adipose tissue of retrosternal localization remains out of research focus. This pool of fat cells is formed at the site of the thymic involution and has a significant volume. However, their functional activity and participation in the development of cardiovascular pathology remain unexplored.Aim. To study the morphological characteristics of adipocytes of the retrosternal adipose tissue (RSAT) and their production of adipokines in comparison with epicardial (EAT) and subcutaneous adipose tissue (SCAT) and to investigate their relationships with arterial stiffness parameters in patients who underwent coronary artery bypass grafting.Materials and methods. The study included 17 patients (12 men/5 women aged 40–70 years) with the diagnosed coronary artery disease (CAD) who underwent coronary artery bypass grafting (CABG). Each patient underwent measurement of carotid-femoral pulse wave velocity (PWV) and aortic augmentation index (AIx) with the oscillometric device. Isolated adipocytes were obtained enzymatically from explants of SCAT, EAT and RSAT during coronary artery bypass grafting. The adipocytes were analyzed under the microscope at 200x magnification. The release of adiponectin, leptin and insulin was studied in the adipocyte supernatant after 1 hour incubation using ELISA.Results. It was found that adipocytes of the RSAT are smaller than adipocytes of SCAT: 83.96 ± 2.21 vs 98.62 ± 2.67 μm (p = 0.00002), respectively, and comparable in size to adipocytes of EAT: 86.65 ± 1.33 μm. The release of adiponectin by adipocytes of the RSAT turned out to be comparable to the production of this adipokine in SCAT and EAT, however, adipocytes of the RSAT produce less leptin than SCAT and EAT: 0.26 (0.19; 0.27) ng/l vs 0.37 (0.28; 0.55) (р = 0.01) and vs 0.32 (0.28; 0.44) (р = 0.006) ng/ml, respectively. Furthermore, RSAT produce less insulin than SCAT and EAT: 1.56 (1.03; 2.08) vs 1.70 (0.99; 2.18) ng/ml, (р = 0.0022) and 1.76 (1.16; 2.40) ng/ml (р = 0.006), respectively.A positive correlation was found between the secretion of leptin by adipocytes of the RSAT and the AIx (rs = 0.52, p = 0.046). An inverse relationship was found between insulin secretion by retrosternal adipocytes and PWV rs = –0.55, p = 0.035). There was no relationship between the size of the retrosternal adipocyte or hypertrophy of the thymic adipocytes (more than 100 μm) and the production of leptin and insulin and arterial stiffness parameters. Conclusions. The data of our pilot study show that adipocyte hypertrophy of the retrosternal AT is not a significant marker of adipokine production disturbance. The observed relationships suggest that an increase in leptin production and reduced insulin secretion by retrosternal AT may contribute to the formation of adipokine-related arterial stiffness. Based on the data obtained, it can be assumed that adipokines produced by the retrosternal AT can participate in the formation of arterial stiffness in patients with coronary artery disease.

Aim. To assess the potential of stress tomographic radionuclide ventriculography (T-RVG) in long-term prognosis of left ventricular (LV) re-remodeling after surgery of ischemic cardiomyopathy.Material and methods. Thirty patients with ischemic cardiomyopathy, before surgical treatment, underwent resting T-RVG and with increasing doses of dopamine (5/10/15 pg/kg/min (5 min/dose). All patients underwent two-dimensional echocardiography before surgery, in the short- (7-14 days) and long-term postoperative period. In the long-term postoperative period (476±36 days), the patients were divided into two groups: group 1 (n=19) — patients with ongoing LV remodeling (increase in the LV end-systolic volume (ESV) or decrease 10%.Results. The results revealed significant differences between the groups in the dynamics (Δ) of the LV ejection fraction (EF) (%) (2 (2;8); 11 (5;12), p=0,02), peak ejection rate (%) (32 (14;51); 63 (34;79), p=0,009), LV dyssynchrony (PSDo (3 (0;7); -2 (-9;3), p=0,004); Entropy (%) (2 (-1;6); 0 (-4;2), p=0,01)). Univariate regression showed that ΔLVEF (odds ratio (OR), 0,88; confidence interval (CI), 0,8; 0,97; p=0.008), ΔLVPSD (OR, 1,13; CI, 1,03; 1,25; p=0,005), and coronary stenosis >75% (OR, 4,25; CI, 1,57; 11,48; p=0,001) had a predictive value. According to the ROC-analysis, the sensitivity, specificity, and AUC were 87%, 64% and 0,727 for ΔLVPSD (threshold >-1); 84%, 46% and 0,691 for coronary stenosis >75% >75% (threshold >2); 65%, 82% and 0,674 for ΔLVEF (threshold ≤4), respectively. The logistic model, which included these parameters and the presence of diabetes, showed a significantly greater AUC (0,907, p

Metastases to the heart are extremely rare, and the reported incidence of cardiac metastasis at autopsy ranges from 1.5 to 21.8 %. In cancer patients, cardiac metastases are usually difficult to diagnose unless the patients do not complain of any related symptoms. Common tumors with cardiac metastasis potential are usually carcinomas of the lung, breast, and malignant lymphoma. The prognosis of a metastatic heart tumor is unfavorable. The average life expectancy for patients with this diagnosis is less than six months. In addition, surgical treatment of primary cardiac tumors or metastatic cardiac tumors is associated with high risk of perioperative lethality. Case report. We present a rare case of cervical cancer metastasis to the heart in a 33-year-old woman. Cytological examination revealed no evidence of disease recurrence 14 months after the completion of external beam radiotherapy. Echocardiography showed a mass in the outflow tract of the right ventricle and findings of severe pulmonary hypertension. omputed tomography and magnetic resonance imaging revealed a large right ventricular thrombus. The patient underwent surgery with artificial circulation. Pathohistological and immunohistochemical studies revealed metastasis of squamous cell carcinoma. The control echocardiography showed decrease in pulmonary hypertension. No evidence of right ventricular mass was detected. Conclusion. Cardiac metastasis should be included in the differential diagnosis in patients with complaints of dyspnea and chest pain, especially in cases with history of cancer. Surgical treatment of cardiac metastasis contributes to the prevention of cardiopulmonary complications and improvement of survival rates in this group of patients.

Aim. To develop and preclinically test an occluder of the left atrium appendage (LAA) in experiment on big animals, as prevention treatment of ischemic strokes.Material and methods. The study was done on the pigs “big white” breed, n=7, mass 98±4 kg. The locally Russian-made device and placement equipment were used. The length of occluder itself, packed, is48 mm, opened — 28-32 mm and diameter 31-35 mm. The occluder was placed into LAA via puncture of femoral vein and interatrial septum under x-ray and ulltrasound control. After implanting of the occluder, during 16 weeks the behavior and appetite of animals were controlled. In prospective study the blood was collected for inflammatory response control, and ultrasound examination of the heart. Controls were 3 swings. In 16 weeks the animals were withdrawn from experiment for morpho-functional investigation of the heart. For cytotoxicity study, histology was done of limphatic nodes, liver and kidneys.Results. By ultrasound imaging it was shown that occluder placement did not significantly influence hemodynamics of animals. Blood tests showed nonsignificant changes during the first weeks after surgery, with normalized values in 12 weeks. Autopsy and microscopy did not show significant inflammatory and degenerative changes in the heart, as in internal organs. There was satisfactory “ingrowth” of the occluder with smooth plain surface of endocardium from the side of the left atrium.Conclusion. The experience of occluder preclinical test showed its construction and functional effectiveness for the aim of further usage in patients with high risk of cardioembolic strokes due to LAA thrombosis. The procedure of occluder implanting is simple if the personnel is skilled enough and there is proper equipment.

Objective. The aim of this study was to determine the informative value of dynamic tomoscintigraphy in detection of multivessel coronary artery disease (CAD).Material and methods. Patients with multivessel CAD (n= 16) and healthy volunteers (n= 9) underwent dynamic cardiac single photon emission computed tomography with 99mТс-MIBI at rest and during pharmacological stress-test.Processing of acquired results involved the formation of regions of interest from the cavity and the myocardium of the left ventricle used to create activity-time curves. Coronary flow reserve index was defined as a quotient of two ratios of the mean counts from the myocardial region to the integral activity in the left ventricular cavity for the studies performed during pharmacological stress test and at rest.Results. The mean values of coronary flow reserve index were 1.86 (1.59; 2.2) in group of healthy volunteers and 1.39 (1.12; 1.69) in patients with multivessel CAD. When the value of this index was less than 1.77, the method allowed for detection of three-vessel CAD with the sensitivity and specificity rates of 81.8% and 66.7%, respectively.Conclusion. Performing the standard myocardial perfusion scintigraphy in combination with the method of coronary flow reserve index assessment allows for enhancement of the diagnostic value of scintigraphic approach in the evaluation of coronary circulation disturbances in multivessel CAD.

The use of laser radiation in cardiac surgery allows to provide more effective and targeted care for patients with ischemic heart disease. The article summarizes the multistage teamwork of several research centers in Tomsk on determination of the most effective type of laser and techniques of cardiac surgery using lasers. The study had an experimental and a clinical phase. In the experimental phase, effectiveness of various laser types for indirect laser myocardial revascularization was assessed, including carbon dioxide, neodymium, and a semiconductor laser types. During clinical phase, efficacy of clinical use of semiconductor laser in various timepoints after surgery was evaluated. The experimental phase revealed that semiconductor laser provides the best neoangiogenesis efficiency, minimal myocardial damage and ease of use. During clinical phase, its safety for a patient was established and a significant clinical benefit was observed.