REVIEWS AND LECTURES
The emergence of new COVID-19 infection aggravated the existing issues and gave rise to new challenges associated with the impact of viruses on the atherosclerotic process and development of cardiovascular complications. Atherosclerosis is a multifactorial disease and its progression is largely determined by dyslipidemia and chronic low-grade systemic vascular inflammation. There are a number of viruses known to be involved in maintaining the inflammatory state through the prolonged viral persistence and replication in the macrophages whose plasticity changes due to the infection. The viruses can trigger the pro-atherogenic cytokine response through the diverse macrophage-dependent mechanisms. There is lack of data regarding impact of viral infections on the monocyte/macrophage plasticity and possible control of inflammation in atherogenesis. It is still unclear whether the relationships between the viral diseases and atherosclerosis are causal or merely associative. In this review, we summarize and critically analyze the current state of knowledge regarding the virus-related mechanisms promoting atherosclerosis.
Endothelial progenitor cells (EPCs) are the cells that play a key role in maintaining vascular integrity and repairing endothelial damage. It has been shown that EPCs can differentiate into mature endothelial cells and are also capable of producing various regulatory growth factors and cytokines. There are many studies focusing on the associations between coronary artery disease and circulating EPCs. However, it is still challenging to use EPCs for the development of diagnostic and treatment algorithms in cardiovascular diseases. This review presents data on EPCs subtypes, methods for obtaining them, biological characteristics of cell populations, and the factors of EPCs mobilization to the site of injury in cardiovascular diseases.
The review of literature is devoted to the analysis of prospects for using breast milk in neonatology, pediatrics, and pediatric cardiology to optimize the postnatal growth and development of children born prematurely.
The article describes the results of analyzing the available literature concerning specifics of pharmacotherapy for hypertension in elderly patients and patients with metabolic syndrome and diabetes mellitus. Authors present statistical data on the prevalence of hypertension among elderly patients and the incidence of obesity and diabetes in the Russian Federation. The paper highlights the characteristics of clinical course of hypertension in the older age group including the predominance of isolated systolic hypertension, vascular stiffness, and increased endothelial dysfunction. The need for administration of antihypertensive drugs to reduce the risk of complications and improve the quality of life even in older patients is confirmed. The analysis of data from numerous large studies allowed the authors to identify the main principles for selecting antihypertensive drugs in elderly patients. Slow calcium channel blockers, angiotensin converting enzyme inhibitors, and low-dose diuretics should be prescribed as first-line drugs. At the next stage of treatment, in case of unsatisfactory results of initial therapy, the addition of mineralocorticoid receptor antagonists, alpha-blockers, and selective imidazoline receptor agonists should be considered. The main approaches to antihypertensive therapy in patients with metabolic syndrome and diabetes mellitus are described. The authors note the fact of unfavorable impact of metabolic syndrome on cardiovascular system, which provides rationale for aggressive treatment of hypertension in such clinical cases where several drugs may be used to achieve a stable antihypertensive effect. Diuretics, angiotensin-converting enzyme inhibitors, and angiotensin receptor blockers are recommended as first-line antihypertensive pharmacotherapy in these patients. The authors argue in favour of the use of antihypertensive drug combinations in one dosage form as one of the effective ways to solve the problem of adherence to treatment in elderly patients and patients with concomitant metabolic disorders.
CLINICAL STUDIES
Introduction. The transcription factor forkhead box protein P3 (FoxP3) is a major regulator of T-regulatory (Treg) lymphocytes and may be expressed in T-conventional (Tconv) lymphocytes at the stage of their activation. The aim of the present study was to evaluate the quantities and features of FoxP3+ Tconv and Treg lymphocytes and their relationships with the parameters of lipid metabolism in patients with chronic coronary artery disease (CAD) depending on the severity of coronary atherosclerosis.
Material and Methods. The study comprised 14 patients (8 men and 6 women) aged 66.5 ± 9.0 years with verified chronic CAD. All the patients underwent coronary angiography and assessment of atherosclerosis severity by calculation of Gensini Score index (GS). Patients were divided into the following groups: group 1 had GS < 20; group 2 had GS ≥ 20. The absolute and relative counts of FoxP3+ Treg and Tconv lymphocytes and degree of FoxP3 nuclear translocation were evaluated in all patients by imaging flow cytometry. Concentrations of insulin, proprotein convertase subtilisin/kexin type 9 (PCSK9), and sortilin were assessed using enzyme-linked immunosorbent assay. Parameters of glucose metabolism and serum lipid spectrum were determined by the standard methods.
Results. Counts of Treg and Tconv lymphocytes did not differ between groups of patients with different severity of atherosclerosis. However, patients with GS ≥ 20 had lower intensity of nuclear FoxP3 fluorescence in Treg and Tconv lymphocytes. GS index in the entire group of CAD patients tended to be negatively associated with the fluorescence intensity of FoxP3 in the nuclei of Treg (rs = –0.476) and Tconv lymphocytes (rs = –0.526). Multiple correlations existed between the quantitative and qualitative parameters of FoxP3+ Treg and FoxP3+ Tconv lymphocytes and metabolic parameters such as concentrations of PCSK9, sortilin, apolipoprotein B, and triglycerides/HDL cholesterol ratio.
Conclusion. FoxP3 fluorescence intensity in the nuclei of T conventional lymphocytes was more sensitive marker of immunoregulatory imbalance in chronic CAD compared to counts of FoxP3+ T cells in the peripheral blood, which remained nearly unaltered with the increase in atherosclerosis severity. At the same time, markers of lipid metabolism were tightly associated with both quantitative and qualitative features of FoxP3+ T-lymphocytes.
Objective. To study the features of local and systemic production of interleukin-19 in patients with atherosclerosis.
Material and Methods. The study comprised a total of 46 patients (26 women and 20 men) treated for arterial hypertension in the therapeutic department of Republican Clinical Hospital named after G.Y. Remishevskaya. The mean age of subjects was 63.4 ± 3.2 years. The control group included 40 patients (23 women and 17 men aged 44.7 ± 5.5 years) who did not have atherosclerosis. Samples of atherosclerotic plaques and venous blood were examined. Atherosclerotic plaques were obtained by endarterectomy and then subjected to homogenization followed by enzymatic hydrolysis for 1 h at 37 °C with collagenase IV in the presence of proteinase III inhibitors. The serum levels of cytokines (in the control group and in patients with atherosclerosis) and in the atherosclerotic plaque homogenate (in patients with atherosclerosis) were determined by ELISA. To assess the cytokine-producing capacity of blood leukocytes and white blood cells isolated from atherosclerotic plaques, spontaneous and phytohemagglutinin (PHA)-induced cytokine production was determined when the cells were cultured in RPMI-1640.
Results. The serum levels of IL-19 did not significantly differ between the patients with atherosclerosis and the control group. A statistically significant two-fold increase in the spontaneous expression of IL-19 by blood leukocytes was observed in the group of patients with atherosclerosis in comparison with the control group. When comparing the contents of IL-19 in blood serum and atherosclerotic plaque homogenate in patients with atherosclerosis, no statistically significant differences were found (p = 0.182). The level of PHA-induced IL-19 production by the atherosclerotic plaque white blood cells was significantly lower than that of blood leucocytes.
Conclusion. The study showed that the reserve capacity for IL-19 synthesis in the atherosclerotic plaque white blood cells decreases leading to the progression of inflammation. The obtained results suggest that IL-19 plays the anti-atherogenic role and its production is involved in the maintaining the mechanisms for down-regulation of inflammation in atherosclerotic plaques.
Purpose. To characterise phenotypic heterogeneity of renal macrophage infiltration and its relationships with clinical and medical history data in patients who died at different times after myocardial infarction (MI).
Material and Methods. We analyzed the material (kidney sections) collected from patients (n = 30) who died from type 1 MI. Renal macrophage infiltration was assessed by the immunohistochemistry method using antibodies to CD68, CD80, CD163, CD206, and stabilin-1.
Results. The study included patients with MI aged 74.8 ± 9.8 years. ST-segment elevation myocardial infarction (STEMI) was diagnosed in 87% of patients; the creatinine level was 115.1 ± 79 μmol/L at admission to hospital. The study showed a significant heterogeneity of macrophage phenotypes in renal tissue: the counts of CD163+, CD68+, CD206+, CD80+, and stabilin-1+ cells were 55 (27; 55), 30 (27; 56), 4 (2; 6), 3 (2; 5), and 2 (1; 3) per field of view, respectively. The CD163+ and CD68+ macrophages were predominant cell types in patients who died within three days after MI onset (p < 0.05). In case of fatal outcome that occurred after three days of MI, the count of CD163+ cells was the highest and exceeded the number of СD68+ cells, which, nevertheless, prevailed over other cell phenotypes (p < 0.05). Starting from day 4 of MI, the counts of CD206+ cells decreased from 6 (5; 8) to 2 (1; 2) similarly to a decrease in CD80+ count from 5 (3; 5) to 2 (1; 2) (p < 0.05). The rate of adverse cardiovascular complications and the severity of coronary lesions were associated with CD80+ and CD206+ cell counts; the development of left ventricular aneurysm was associated with the numbers of stabilin-1+ and CD163+ cells.
Conclusion. Renal macrophage infiltration was characterized by a pronounced cellular heterogeneity that depended on the timing of death after MI. The CD163+ and CD68+ cells predominated at the early stages of MI; the CD163+ cells were predominant at the later stages. The CD80+ and CD206+ cell counts changed quantitatively, decreasing from day 4 of MI. The presence of multiple correlation relationships between the cells of macrophage lineage in the kidneys and the development of adverse cardiovascular complications in patients with MI provides rationale for further studies.
Relevance. Cardiotrophin-1 (CT-1) is a member of interleukin-6 (IL-6) superfamily and is associated with cardiovascular pathology. The production of CT-1 increases in response to myocardial wall stretching and increase in its rigidity and is also modulated by a wide range of neurohormones and peptides, which allows to monitor CT-1 as a marker of biomechanical stress. However, the prognostic significance of CT-1 in patients with diastolic heart failure with hypertrophic cardiomyopathy (HCM) remains poorly understood.
Objective. To study the blood serum cardiotrophin-1 contents and their relationships with NT-proBNP in patients with obstructive hypertrophic cardiomyopathy and in patients with severe left ventricular (LV) dysfunction.
Material and Methods. The study comprised a total of 76 patients with obstructive HCM and 31 patients with severe LV dysfunction. The group of patients with HCM comprised patients with obstructive form; the group of patients with severe LV dysfunction included patients with the third type of post-infarction LV remodeling and ejection fraction (EF) of less than 30%. The determination of cardiotrophin-1 and highly sensitive C-reactive protein was carried out by the enzyme immunoassay. The study of NT-proBNP content in blood serum was performed by multiplex immunoassay using the FLEXMAP 3D Luminex Corporation system.
Results. The content of cardiotrophin-1 in the blood serum of patients with obstructive HCM was higher than in the group of patients with severe LV dysfunction. The study of NT-proBNP concentrations in the blood serum showed increases in the content in both groups of patients. The median concentrations of NT-proBNP and C-reactive protein in patients with severe LV dysfunction were increased compared to the median concentration in patients with obstructive HCM.
Conclusion. The study showed an increase in cardiotrophin-1 content in the blood serum in patients with obstructive HCM with chronic diastolic heart failure. The increase in cardiotrophin-1 content was directly associated with the increase in NTproBNP level in patients with obstructive HCM with chronic diastolic heart failure.
Background. There is currently no commonly accepted strategy for limiting the reperfusion injury that occurs after revascularization in patients with myocardial infarction. This study aimed to investigate the efficacy of a promising cardioprotective method.
Material and Methods. Patients with acute anterior ST-segment elevation myocardial infarction (STEMI) (n = 87) were included in an open-label prospective randomized controlled trial. Control group comprised patients with STEMI who underwent only primary percutaneous coronary intervention (PPCI) (n = 44). Patients of intervention group (n = 43) underwent PPCI and remote ischemic perconditioning combined with postconditioning (RIC). The efficacy of RIC was assessed based on cardiac magnetic resonance (CMR) imaging data.
Results. The medians of left ventricular (LV) infarct size were significantly higher in patients of control group: 44.8 (33.6; 55.5) versus 52.7 (35.5; 73.9) mL (p = 0.039) at day 10 after STEMI and 34.0 (25.8; 39.8) mL versus 46.0 (32.8; 55.0) mL six months after STEMI in control and intervention groups, respectively (p = 0.004). The groups of patients did not differ in the sizes of area at risk relative to the total LV myocardial volume: 40 (35; 45) and 43 (34; 49)% in control and intervention groups, respectively (р = 0.232). The groups significantly differed in the ratios of infarct size to area at risk: 70.3 (65.1; 86.6)% in control group versus 63.5 (52.7; 72.0)% in intervention group (р = 0.014) as well as in the myocardial salvage indexes: 29.7 (13.5; 34.9)% in control group versus 36.5 (28.0; 47.3)% in intervention group (р = 0.014). The study showed the tendency to greater LV myocardial salvage in intervention group versus control group at six-months follow-up (р = 0.073). The groups significantly differed in the medians of microvascular obstruction volume: 1.9 (1.4; 2.9) mL in intervention group versus 2.5 (1.8; 8.1) mL in control group (p = 0.049) as well as in the proportions of microvascular obstruction in the LV myocardium: 0.94 (0.79; 1.37)% in intervention group versus 1.50 (0.89; 3.66)% in control group (р = 0.046).
Conclusion. The RIC method combined with PPCI contributed to the limitation of infarct and microvascular obstruction sizes and was associated with an increase in the myocardial salvage index in STEMI patients.
Introduction. Macrophages are the center of homeostasis regulation in endometrioid heterotopia tissue. Being one of the most important elements in understanding the pathogenesis of endometriosis, macrophages control the changes in the cooperation of cellular elements.
Aim. The aim of the study was to assess the location, nature, and strength of correlation relationships between the macrophages/ siderophages and other cell populations in the endometrioid cysts wall at various stages of their formation.
Material and Methods. The study comprised 57 patients with a histologically verified diagnosis of endometrioid ovarian cyst. All the studied endometrioid cysts were divided into “young”, “mature”, and “old” based on the morphological features. The macrophages/siderophages, lymphocytes, neutrophils, and eosinophils were counted in 10 visual fields in the cyst wall after staining with hematoxylin and eosin at ×400 magnification at the different layers of cyst wall.
Results. The dynamics of changes in the location, direction, and strength of correlations showed that the functional destruction of macrophage cell center occurred during maturation and aging of the ovarian endometrioid cyst. This process was caused by an insufficient vascularization of endometrioid heterotopia, increasing pressure inside the cyst, and the gradual compaction of underlying fibrous layer, which lead to the atrophy of endometrioid lining and inability of macrophage cell center to maintain homeostasis. These changes caused a complete depletion of macrophage cell center due to macrophage polarization and subsequent formation of siderophages.
Conclusion. In the absence of endometrium-associated macrophage pool renewal, endometrioid heterotopia eventually subside due to the destruction of macrophage cell center that controls its homeostasis.
Aim. The aim of the study was to differentiate the endotypes in allergic rhinitis by key allergy markers in a mixed group of patients.
Material and Methods. The study comprised a total of 48 patients, men and women, aged 18-60 years suffering from three endotypes of allergic rhinitis including the classic, local, and dual allergic rhinitis. The standard diagnostics of allergic rhinitis included taking a history of allergies, family history of allergic disease, video rhinoscopy, serum total IgE level assessment, allergy skin tests to house dust mite and pollen allergens, and study of eosinophilic inflammation parameters (eosinophil cationic protein, interleukin-5 (IL5), and eosinophil counts in blood and nasal secretion).
Results. Based on total IgE level, the general group of patients was divided to two subgroups: subgroup 1 comprised patients with high IgE level (n = 22); subgroup 2 comprised patients with low IgE level (n = 26). Most of patients in these groups had contradictory results of allergy skin tests i.e. positive allergy skin test results in case of high IgE level (group 1) and vice versa. Cluster analysis-based exminations of general group allowed to categorize three subgroups of patients: patients with classic allergic rhinitis (n = 22), local allergic rhinitis (n = 22), and dual allergic rhinitis (n = 4). Besides, an increased rate of anxiety disorder was found in patients with local allergic rhinitis (p < 0.001).
Conclusion. The obtained data showed promise for a new research trend in studying allergic rhinitis endotypes, namely: investigation of neuroimmune relationships in allergic tolerance disruption in the presence of this pathology.
The consistently high frequency of pathology of urinary system in children dictates the need to find new methods for the treatment and prevention of pyelonephritis.
Goal. To study clinical and laboratory indicators of health status in children with chronic pyelonephritis living in the industrial city of Tomsk and evaluate the effectiveness of various rehabilitation treatment regimens.
Material and Methods. The kidney and urology examinations were performed in 58 children with a diagnosis of chronic pyelonephritis aged 7 to 12 years. Two treatment schemes including administration of mineral water and physiotherapy were used.
Results and Discussion. The following symptoms were detected before treatment: oxaluria in 22.41% of children, microhematuria in 17.24% of children, significant increase in serum and morning urine nitrate/nitrite levels, and microalbuminuria suggesting the instability of cell membranes and inflammatory process in renal tissue.
Conclusion. The administration of low-mineralized magnesium-sodium chloride-sulfate water in combination with physical therapy, manual massage, sapropel applications, interference therapy, and enteric oxygen therapy lead to normalization of clinical and laboratory health status indicators in the main group of patients.
Purpose. To compare the results of biatrial (BA) and left atrial ablation (LAA) performed in patients with long-standing persistent atrial fibrillation (AF) with concomitant coronary artery disease (CAD) with indication for coronary artery bypass grafting (CABG).
Material and Methods. A prospective, randomized, single-center, blinded study was conducted on the basis Meshalkin National Medical Research Center in the period from 2016 to 2019. A total of 116 patients with long-standing persistent AF and CAD were randomized into two groups: BA + CABG group (n = 58) and LAA + CABG group (n = 58). Patients of both groups underwent CABG surgery with the chosen atrial ablation technique (LAA or BA).
Results: BA technique proved to be more effective in maintaining sinus rhythm (58%) compared with isolated LAA (31%) at 24 months (p = 0.019) after surgical treatment of long-standing persistent AF with concomitant CABG.
Conclusion: BA technique was more effective than isolated LAA in the late postoperative period of 24 months.
Aim. To demonstrate the capabilities of magnetic resonance imaging (MRI) and magnetic resonance (MR) angiography in the complex examination of patients with various types of transposition of great arteries (TGA) at the pre- and postoperative stages.
Material and Methods. A total of 38 MRI studies of the heart and blood vessels were performed in 33 patients with various forms of transposition of great vessels.
Results. The main purpose of MRI was to identify postoperative complications after arterial switch operation for simple TGA. Cicatricial changes in the wall of the left ventricle were revealed in two patients, which was the basis for coronary angiography. Coronary angiography revealed no significant coronary artery stenosis requiring surgical intervention. The aortic root was dilated to an average of + 2.85 Z-score in six patients after arterial switch operation, which required further dynamic observation. Stenosis of the branches of the pulmonary artery due to the use of the Lecompte maneuver was revealed in one patient. Heart catheterization was performed according to the results of MRI. Invasive pressure measurement revealed neither significant stenosis nor indications for surgical treatment. MRI data were used as one of the criteria for anatomical correction readiness in group of patients with congenitally corrected transposition of the great vessels, along with data of echocardiography and heart catheterization.
Conclusion. MRI and MR angiography are the “gold standard” in the pre- and postoperative examination of patients with various forms of TGA . Using MR angiography, it is possible to carry out morphometry and clarify the spatial arrangement of vessels including that after correction of TGA. In most cases, MRI allows to correctly differentiate the morphology of the heart chambers and their relative position. It also allows to perform volumetry and to assess the parameters of local and global contractile function of the ventricles, which is essential for preoperative assessment and dynamic observation at all stages of correction.
CLINICAL CASES
The article demonstrates the first clinical case of using the vascular stent graft in renal artery prosthetics in the framework of hybrid treatment of a patient with Stanford B type aortic dissection with renovisceral debranching and subsequent aortic endoprosthetics. Currently available approaches to nephropothecation in prosthetics of renal arteries, surgical technique for using the graft, and the features and advantages of its use are described. The place of this new technique in the surgery of thoracoabdominal aorta is discussed.
Prosthetic valve endocarditis is a clinically severe pathology, which, unless timely treated, rapidly leads to the development of heart failure. The severity of the disease is caused by the fact that the microorganisms and toxins bypass biological barriers and constantly enter the bloodstream, which subsequently results in sepsis with the development of systemic embolism and multiple organ failure. The conservative antibiotic therapy is often ineffective due to the location of the infectious focus in the avascular zone. The operations for prosthetic infectious valve endocarditis are technically challenging and require high qualifications of the operating surgeon. The article presents a clinical case of surgical treatment for infectious prosthetic endocarditis of the aortic valve. The combined treatment with air-plasma flow and exogenous nitric oxide (NO) using the Plazon device without any antiseptic solutions was used as a method for the debridement of infectious site.
ANNIVERSARIES
ISSN 2713-265X (Online)