[Respiratory disorders of post-COVID-19 syndrome].

AIM: Assess the functional state of trespiratory system and effectiveness of therapeutic tactics for broncho-obstructive syndrome (BOS) in patients in the post-COVID period. MATERIALS AND METHODS: A two-center cohort prospective study included 10 456 and 89 patients, respectively. A comprehensive assessment of the respiratory system included clinical, laboratory and functional data, spirometry, body plethysmography, and a study of diffusive capacity of the lungs (DLCO). Therapy consisted of budesonide suspension or fixed combination beclomethasone dipropionate/formoterol (EMD BDP/FORM). RESULTS: The frequency of BOS in the cohort was 72% (7497 patients). In 13% (n=974) of cases, bronchial asthma was diagnosed for the first time, in 4.4% (n=328) - chronic obstructive pulmonary disease. Risk factors for the development and decrease in DLCO in the post-COVID period were identified. In the group of complex instrumental examination of lung function, the absence of violations of spirometric data and indicators determined by body plethysmography was determined. CONCLUSION: Risk factors for BOS in post-COVID period are atopy, a history of frequent acute respiratory infections, smoking, blood eosinophilia, moderate and severe forms of COVID-19. The advantage of a fixed combination of EMD BDP/FORM in MART mode compared with nebulized suspension budesonide + solution of salbutamol in treatment of BOS was shown. Risk factors for DLCO disorders were established: severe COVID-19, hospitalization in the intensive care unit, the need for additional oxygen therapy.

New Tissue-Engineered Vascular Matrix Based on Regenerated Silk Fibroin: in vitro Study.

The aim of the study was to make a vascular patch based on regenerated silk fibroin (SF) and study its physical and mechanical characteristics, biocompatibility and matrix properties in comparison with polyhydroxybutyrate/valerate/polycaprolactone with incorporated vascular endothelial growth factor (PHBV/PCL/VEGF) and commercial bovine xenopericardium (XP) flap in experiments in vitro. Materials and Methods: Tissue-engineered matrices were produced by electrospinning. The surface structure, physical and mechanical characteristics, hemocompatibility (erythrocyte hemolysis, aggregation, adhesion and activation of platelets after contact with the material) and matrix properties of vascular patches (adhesion, viability, metabolic activity of EA.hy926 cells on the material) were studied. Results: The surface of SF-based matrices and PHBV/PCL/VEGF-based tissue engineered patches had a porous and fibrous structure compared to a denser and more uniform XP flap. The physical and mechanical characteristics of SF matrices were close to those of native vessels. Along with this, tissue-engineered patches demonstrated high hemocompatible properties, which do not differ from those for commercial XP flap. Adhesion, viability, and metabolic activity of EA.hy926 endothelial cells also corresponded to the previously developed PHBV/PCL/VEGF matrix and XP flap, which indicates the nontoxicity and biocompatibility of SF matrices. Conclusion: Matrices produced from regenerated SF demonstrated satisfactory results, comparable to those for PHBV/PCL/VEGF and commercial XP flap, and in the case of platelet adhesion and activation, they outperformed these patches. In total, SF can be defined as material having sufficient biological compatibility, which makes it possible to consider a tissue-engineered matrix made from it as promising for implantation into the vascular wall.

[Screening analysis of proteolytic enzymes and their inhibitors in the leaflets of epoxy-treated bioprosthetic heart valves explanted due to dysfunction]. / Skriningovyi analiz proteoliticheskikh fermentov i ikh ingibitorov v stvorkakh époksiobrabotannykh bioproteznykh klapanov serdtsa, éksplantirovannykh po prichine disfunktsii.

Bioprosthetic heart valves (BHVs) are known for their lower thrombogenicity rates and excellent hemodynamic parameters similar to native valves. However, the lifespan of these medical devices is limited to 15 years due to the structural valve degeneration. One of the mechanisms underlying functional impairment and calcification of BHVs includes proteolytic degradation of biomaterials. However, proteases found in xenogeneic BHVs tissue remain poorly studied. In this study using the dot blot assay, we have performed a screening analysis of proteolytic enzymes and their inhibitors in the leaflets of five BHVs explanted due to their dysfunction. Five aortic valves (AVs) explanted due to calcific aortic valve disease were studied as a comparison group. The results of the study have demonstrated that at least 17 proteases and 19 of their inhibitors can be found in BHVs. In the AVs 20 proteases and 21 their inhibitors were identified. Small quantitative differences were noted between proteomic profiles of the BHVs and AVs. Matrix metalloproteinases (MMPs) were expressed in BHVs and AVs at comparable levels, but the level of tissue inhibitors of metalloproteinases-1/-2 and RECK protein in implant tissues was lower than in natural valves. Probably, excessive activity of MMPs cannot be counterbalanced by their inhibitors in BHVs and therefore MMPs can degrade prosthetic biomaterial. Moreover, the detection of a wide range of proteolytic enzymes and their inhibitors in the degenerated BHVs suggests the existence of several pathophysiological pathways that can lead to structural valve degeneration.

A Technology for Anti-Thrombogenic Drug Coating of Small-Diameter Biodegradable Vascular Prostheses.

The aim of the study was to develop a technology for anti-thrombogenic drug coating of biodegradable porous scaffolds and to evaluate the physicomechanical and hemocompatible properties of functionally active vascular prostheses with and without a drug coating. MATERIALS AND METHODS: Vascular prostheses from polyhydroxybutyrate/valerate and polycaprolactone with the incorporated vascular endothelial growth factor, the main fibroblast growth factor, and the chemoattractant SDF-1α were made by emulsion electrospinning. Additional surface modification of the prostheses was carried out by forming a hydrogel coating of polyvinylpyrrolidone capable of binding drugs as a result of complexation. Unfractionated heparin and iloprost were used as anti-thrombogenic drugs. RESULTS: We show that after the modification of vascular prostheses with heparin and iloprost, a 5.8-fold increase in the Young's modulus value was noted, which indicated a greater stiffness of these grafts compared to the unmodified controls. Platelet aggregation on the surface of heparin + iloprost coated vascular prostheses was 3.3 times less than that with the unmodified controls, and 1.8 times less compared to intact platelet-rich plasma. The surface of vascular prostheses with heparin and iloprost was resistant to adhesion of platelets and blood proteins. CONCLUSION: Drug (unfractionated heparin and iloprost) coating of the surface of biodegradable prostheses significantly improved the anti-thrombogenic properties of these grafts but contributed to the increased stiffness of the prostheses.

[Infective Endocarditis Causing Native and Prosthetic Heart Valve Dysfunction].

Infective endocarditis (IE) is the disease that has high inhospital mortality. Heart valves dysfunction - both native and prosthetic - is the primary IE complication requiring a surgical intervention. The IE causes and its course have been discussed in this review. In particular, the role of concomitant infectious foci in the formation and development of IE have been considered, the mechanisms of mutual transition of subacute and acute clinical forms have been described. Modern diagnostic principles and methods based on the Duke criteria system have been mentioned, as well as the difficulties that follow the patient's clinical status evaluation. The normobiotic microbiota participation, as well as the possibilities for their identification using blood culture and PCR technique, have been closely reviewed. According to modern researches and publications, there have been made the conclusion about the contribution of obligate anaerobic bacteria, fungi and viruses to the development of endocarditis. There have been described the hypothesis about the presumptive strategy for the cardiac dysfunction formation as a result of the IE causative agents cells metabolic activity based on a literature data analysis in the article: vegetation formed by Staphylococcus aureus can lead to the heart valve stenosis, and the influence of hyaluronidases, collagenases on a heart valve structure can lead to regurgitation. The pathogens cells ability to avoid the human immune system response is caused by the biofilms, fibrin vegetations formation and the enzymes production - cytotoxins (streptolysins, leukocidin, etc.). It has been suggested that the mediators of inflammation and leukocyte cells participate in the destruction of native and prosthetic tissues due to an IE pathogens inaccessibility for immunocompetent cells.

Endothelialization of Polycaprolactone Vascular Graft under the Action of Locally Applied Vascular Endothelial Growth Factor.

We have previously developed a polycaprolactone (PCL) vascular graft with incorporated vascular endothelial growth factor (VEGF). Functioning of the PCL/VEGF graft in rat circulatory system over 1, 3 and 6 months after implantation into abdominal aorta was tested. Graft patency and formation of vascular wall elements were assessed histologically and by immunofluorescence staining for von Willebrand factor, CD31, CD34, and collagens I and IV and DAPI staining. Local application of VEGF promoted endothelialization and improved patency of the graft. The wall of the PCL/VEGF graft underwent remodeling due to active cellular infiltration and the extracellular matrix deposition.

[Calcification Patterns of the Components of the Cardiovascular System and Their Substitutes: Composition, Stucture and Localization of Calcific Deposits].

Calcification of cardiovascular tissues and biological substitutes results in abnormal biomechanics, causing stenosis or tissues ruptures. Therefore, the understanding of calcification pathways will facilitate the development of strategies for calcification risk reduction. Even though calcification pathways have been studied since the mid-80s and are widely described in the medical literature, there is no consensus on the cause-and-effect relationships in this pathological process. The current review covers the composition, structural aspects and specific localization of calcific deposits in native heart valves and blood vessels, bioprosthetic heart valves treated with glutaraldehyde. Moreover, experimental data on the composition of in vivo and in vitro calcification are presented. These characteristics of calcific deposits provide new insights in the calcification pathways. According to the results of the literature review, one may conclude that cell death, microfracture of the surrounding tissues with the overall biochemical imbalance may potentiate the calcification process. Moreover, the progression of calcification process is associated with the accumulation of mechanical stress.

Biocompatibility and Structural Features of Biodegradable Polymer Scaffolds.

We performed a comparative analysis of physicochemical properties and biocompatibility of scaffolds of different composition on the basis of biodegradable polymers fabricated by casting and electrospinning methods. For production of polyhydroxyalkanoate-based scaffolds by electrospinning method, the optimal concentration of the polymer was 8-10%. Fiber diameter and properties of the scaffold produced by electrospinning method depended on polymer composition. Addition of polycaprolactone increased elasticity of the scaffolds. Bio- and hemocompatibility of the scaffolds largely depended on the composition formulation and method of scaffold fabrication. Polylactide introduced into the composition of polyhydroxybutyrate-oxyvalerate scaffolds accelerated degradation and increased adhesive properties of the scaffolds.

Use of polycaprolactone grafts for small-diameter blood vessels.

Current trends are toward actively developing approaches of tissue engineering, aimed at creating vascular grafts of small diameter. This is due to the existing in cardiovascular surgery demand for prostheses to be used in coronary artery bypass grafting. The present work was undertaken in order to assess possibilities of using smalldiameter vascular grafts made of biodegradable polymer polycaprolactone by means of electrospinning. The authors studied physico-mechanical properties and structure of polycaprolactone grafts, as well as their thromboresistance and patency after implantation into the vascular bed of rats. The obtained results demonstrated optimal physicomechanical properties of the vascular grafts, their biocompatibility, endothelialisation of the internal surface, and infiltration of the graft's wall by cells with the formation of new tissue, accompanied and followed by the development of an extensive intimal layer in the zones of the anastomoses. Hence, the study showed possibilities of using polycaprolactone grafts as vascular prostheses, however requiring their further modification which would promote and contribute to a decrease in hyperplasia of connective tissue in the graft's lumen.