Aim.      To investigate the relationship between the osmotic fragility of erythrocytes and the course of acute myocardial infarction (MI).

Methods.           An analysis of the osmotic fragility of erythrocytes was conducted using beta-blocker-based osmotic fragility test in sixty-two patients within the first 6 hours after onset of MI symptoms.

Results. The results revealed that the patients with increased erythrocyte osmotic fragility experienced more complications after acute MI, such as left ventricular failure and cardiac arrhythmias (ventricular extrasystoles and ventricular tachycardia) (p = 0.026). Moreover, these patients exhibited greater myocardial injury - the concentration of biomarkers of myocardial necrosis, such as creatine phosphokinase, creatine phosphokinase MB and Troponin I was increased - p = 0.009, p = 0.032 and p = 0.001, respectively. In addition to that, the patients with high osmotic fragility had a larger number of hypokinetic and akinetic segments, high impaired myocardial contractility index, and low ejection fraction. The impaired myocardial contractility index was significantly higher in patients with increased erythrocyte osmotic fragility (1.5 (1.22; 1.75) vs 1.12 (1.0; 1.56), U = 157.5, p = 0.032).

Conclusion. Increased erythrocyte osmotic fragility in patients was associated with greater myocardial injury, manifesting through the higher concentration of biomarkers of myocardial necrosis in blood, as well as higher number of hypokinetic segments.

Aim. To assess the effects of cognitive rehabilitation with dual-task training that involves a cognitive task combined with postural and walking control, as well as electroencephalogram indices in patients in the early postoperative period after direct myocardial revascularization.

Methods. The study enrolled 48 patients scheduled for coronary artery bypass graft surgery. Subjects in this prospective, randomized study were randomized using envelopes to a postoperative cognitive training group (n = 23) and non-training group (n = 25). The cognitive training was carried out daily, starting 3-4 days after the procedure and until the discharge order. Dual tasks training (a cognitive task combined with postural and walking control) lasted 15-20 minutes. All patients were submitted to an extended neurophysiological assessment (psychometric tests and electroencephalogram study) and stabilography 3-5 days before and 8-11 days after coronary artery bypass grafting.

Results. The patients who underwent cognitive training experienced postoperative cognitive dysfunction (POCD) in 39% cases in the early postoperative period after intervention, while the non-training group - in 64%. The relative risk of developing POCD in the non-training group was 2.77 (95% CI: 0.86-8.91, Z = 1.704, p = 0.08). The patients in cognitive training exhibited better cognitive state compared to the preoperative state (Z = 2.58; p = 0.01) in the absence of statistically significant differences in the non-training group. Moreover, type-1 theta power values increased in the non-training group in comparison to the preoperative values, while the cognitive training group did not have a statistically significant difference in theta power.

Conclusion. Positive effects of dual task rehabilitation on the neurophysiological parameters of patients undergoing direct myocardial revascularization were demonstrated. Positive effects include lower frequency of POCD, improved cognitive state and less pronounced cortical dysfunction. The dual task training had proved a suitable training method for this category of patients. Additional studies are required to test the possibility of increasing the duration and intensity of dual task training for stronger recovery effect and improved cognitive and walking performance of patients in the postoperative period after direct myocardial revascularization.

Aim. To analyze the topographic patterns of valvular and atherosclerotic calcification growth.

Methods.           Dysfunctional aortic valves (n = 18) and atherosclerotic plaques (n = 20) were fixed in formalin, postfixed in 1% osmium tetroxide, consecutively stained by 2% osmium tetroxide and 2% uranyl acetate, and embedded into epoxy resin (Epon) with the further grinding and polishing ofthe samples. Upon the counterstaining by lead citrate and sputter coating with carbon, samples were visualized by backscattered scanning electron microscopy. Elemental analysis was conducted via energy-dispersive X-ray spectroscopy. Measurement of Ca/P ratio within the mineral deposits was carried out employing a pool table principle (i.e., in the center of the deposit, in the near and far circumferences (clockwise), and in control regions around the mineral deposit). Topographic patterns of calcifications were modeled using the correlation analysis.             

Results. Significant correlation was revealed between the Ca/P ratio in the deposit center and in the near and far circumferences of deposit in both in valvular (r = 0,35-0,78 - near circumference; r = 0,63-0,69 - far circumference) and atherosclerotic mineral deposits (r = 0,37-0,56 - near circumference; r = 0,48-0,63 - far circumference), suggesting the hierarchical growth of cardiovascular calcification around the initial nucleation sites.

Conclusion.       Valvular and atherosclerotic calcifications development is concentric.

Background.      The application of tissue-engineered constructs that simulate the natural microenvironment of cells, maintain their viability and functional properties, is a new promising route for the treatment of ischemic diseases. However, the mechanisms that ensure the effectiveness of this type of treatment and the principles of choosing the optimal population of progenitor cells remain poorly understood.        

Aim. To study the profile of secretion of proangiogenic growth factors of cardiosphere-derived cell sheet (CS), and to study the effect of their transplantation on postinfarction myocardial vascularization.            

Methods. Assembly of cardiosphere-derived cell sheets were performed on thermosensitive culture plates. Characterization of cell sheets was performed using immunofluorescence staining and a commercial kit for the determination of proangiogenic factors “Mouse Angiogenesis Antibody Array”. The evaluation of the angiogenic properties of the cell graft in vivo was carried out using a rat myocardial infarction model.              

Results. It was found that the cardiosphere-derived cell sheet secrete factors involved in the regulation of vasculo-/angiogenesis. At the same time, the cultivation of cell sheets under hypoxic conditions (3% O2) led to an increase in the secretion of proangigenic factors VEGF and pIgF, fGf-1, FGF-2, endothelin-1, as well as MMP-9, which is involved in extracellular matrix remodeling. Cell sheet transplantation on the epicardial surface of the heart after myocardial infarction ensures cell viability and local increase in capillarization of the damaged area. 

Conclusion. Thus, the application of cardiosphere-derived cell sheets, which have proangiogenic properties and ability to maintain post transplantation cell survival, can be considered as a promising approach for the development of new methods of therapy for heart diseases

Aim. Calcified aortic valve stenosis is the third leading cause of cardiovascular disease. The mechanisms underlying this process remain unclear, however, it is known that they are largely similar to the formation of bone tissue during embryonic development, as well as in the postnatal period during regeneration. There is evidence for the             involvement of Zinc Finger and BTB Domain Containing 16 (ZBTB16) in skeletal development. At the same time, a number of studies carried out on different types of cell cultures indicate a contradictory and ambiguous effect of ZBTB16 on RUNX2 expression. Thus, the aim of this study was to investigate the dynamic variability of ZBTB16 expression, as well as its role in aortic valve calcification.

Methods. The study used different types of mesenchymal cells cultures - aortic valve interstitial cells, umbilical cord mesenchymal stem cells, ligament stem cells and dental pulp stem cells. Changes in ZBTB16 and RUNX2 expression levels                under the influence of osteogenic stimuli, as well as during exogenous activation of ZBTB16, were analyzed using real-time PCR. Expression levels of some osteogenic markers - BMP2,4, COL1A1, IBSP, DLX2, PDK4 - were analyzed in the interstitial cells of the aortic valve.

Results. The results of the study indicate that a significant increase in the expression of ZBTB16 is observed during the induction of osteogenic differentiation of various cell cultures - interstitial cells of the aortic valve, mesenchymal stem cells of           the umbilical cord, stem cells of the ligaments and dental pulp. Apparently, the processes of osteogenic differentiation of aortic valve interstitial cells, in the presence of dexamethasone in cultivation medium, are provided through RUNX2-dependent signaling for the further activation of osteogenic markers.

Conclusion. The study of modulation of cellular signals by ZBTB16, when activating or suppressing the work of a transcriptional factor, in the future may bring us closer to the ability to enhance the regenerative abilities of bone tissue cells or, conversely, prevent calcification of the aortic valve tissues.

Aim. To assess the effectiveness of QMS implemented by Research Institute for Complex Issues of Cardiovascular Diseases (NII KPSSZ) in 2020 and determine the impact of force majeure event (COVID-19 pandemic) on the achievement of the goals and objectives of the organization.

Methods. 11 QMS processes of the NII KPSSZ in 2020 were analyzed according to 98 performance criteria. The following general scientific methods were used for the assessment of QMS: analysis, synthesis, structural and systems analysis.

Results. The overall effectiveness of the QMS in 2020 was 83.5%, for the individual processes it varies from 57% to 100%. Achievement of target indicators in accordance with the criteria reflects the effectiveness of risk management in QMS processes. 27 criteria were added (9 of which were reformulated) as a result of the development of the system and the analysis of work experience in unusual circumstances for year 2021. At the end of 2021, QMS will be analyzed according to 117 criteria for the processes effectiveness.

Conclusion. The presented experience of quality management system functioning in 2020 highlights the significant roles of monitoring of the main processes and performance indicators analysis of scientific and medical organization in the ongoing COVID-19 pandemic. Such analysis is a necessary for decision-making because it allows the organization to fulfill the obligations, maintain conditions for increasing stakeholder satisfaction, monitor risks and assess opportunities associated with the environment and objectives of the organization, and ensure compliance with the standard requirements, regulations and legislation.

Abstract. Chronic heart failure is one of the main contributors to the Global Burden of Cardiovascular Diseases. Despite advances in modern treatment, acute decompensated heart failure (ADHF) incidence is high. Moreover, patients admitted for ADHF encounter renal impairment, which is another predictor of adverse outcome. There are number of biomarkers that allow clinicians to assess the prognosis of the disease in the early stages. The article presents an overview of contemporary biomarkers (utilizing multimarker approach), and identifies the most significant biological markers for evaluating ADHF and worsening renal function.

Modern methods of treating heart failure are similar to the palliative care, since they mostly relieve the symptoms of the disease. The discovery of resident cardiac stem cells gave impetus to the development of “second generation” cell therapy, which quickly moved from animal research to clinical trials with critically ill patients. Many cardiac side population cells have been identified to have stem cells characteristics and some additional individual characteristics, both in vitro and in vivo. The results of clinical studies demonstrated that the stem cell treatment is safe, however, this type of cell-based therapy did not restore cardiac function. Its effects were limited to mildly improving left ventricular systolic pressure and reducing the scar area. Despite that, the promising nature of these therapeutic approaches for heart diseases have contributed to the development of next-generation cell therapy.

The presented literature review is devoted to the cardioprotective capabilities of a new class of antihyperglycemic drugs - sodium-glucose cotransporter 2 inhibitors (SGLT2), which improve glycemic control through an insulin-independent mechanism of action associated with an increase in urinary glucose excretion. The article presents the results of large-scale clinical trials on the use of SGLT2 inhibitors in patients with and without diabetes, and with cardiovascular diseases or multiple cardiovascular risk factors. A number of the most frequently discussed cardiac specific mechanisms mediated by the SGLT2 inhibitor affecting the Abstract           state of the cardiovascular system are presented. Moreover, the article presents the results of a placebo-controlled clinical trial entitled “Empagliflozin reduces mortality in patients with type 2 diabetes at high cardiovascular risk” (EMPA-REG oUtcOmE) to analyze the cardioprotective capabilities of SGLT2 inhibitor empagliflozin in patients with type 2 diabetes and concomitant cardiovascular diseases. The article emphasizes the importance of further research to determine the degree of contribution of the above-mentioned mechanisms to the cardioprotective potential of SGLT2 inhibitors. PubMed database was used to identify relevant studies and systematic reviews.

Prosthetic vascular graft infections, followed by severe complications and high mortality rates, remain one of the main issues in cardiovascular surgery. Therefore, the development of antimicrobial coating for vascular prostheses that is capable of preventing the infection is a very relevant field. This review outlines the main factors of development of antibiotic-resistant bacteria, the main directions in the development of vascular prostheses with an antimicrobial coating, and the prospects for the application of antimicrobial peptides and cationic amphiphiles as antimicrobial coating to develop an infection-resistant vascular prosthesis.

Heart and vascular diseases are responsible for tens of millions of deaths annually, underscoring an urgent need to improve the existing clinical practice in order to benefit patients. Advancement of basic science and technology enables understanding of disease etiology and pathogenesis at a deeper level of complexity. This mini-review article provides a summary of recent methods of cell and molecular biology applicable for current cardiovascular research. Widespread application of these approaches in cardiovascular disease research will be a key factor in the prolonged longevity and life expectancy of the general population.

There is growing research focusing on endothelial cells as separate units of the blood-brain barrier (BBB), and on the complex relationships between different types of cells within a neurovascular unit. To conduct this type of studies, researches use vastly different in vitro BBB models. The main objective of such models is to study the BBB permeability for different molecules, and to advance the current level of understanding the mechanisms of disease and to develop methods of targeted therapy for the central nervous system. The analysis of the existing Abstract in vitro BBB models and their advantages/disadvantages was conducted using the clinical trial data obtained in Russian/foreign countries. In this review, the authors highlight the most relevant assessment parameters and propose a unified classification of in vitro BBB models. According to the performed analysis, there is a tendency to move from 2D BBB models based on semipermeable inserts to 3D BBB spheroid and microfluidic organ-on-chip models. Moreover, the use of human induced pluripotent stem cells instead of animal primary cells will make it possible to reliably scale the results obtained in vitro to conditions in vivo.

At the online meeting of experts held on April 24, 2021, the results of the international multicenter trial EMPEROR-Reduced were considered. Taking into account the beneficial cardiovascular and renal outcomes in patients with chronic heart failure and reduced left ventricular ejection fraction (<40%), and improvement in patient survival rates, a number of proposals and recommendations for widespread implementation of the trial results into practice of treating patients with chronic heart failure were adopted.