The Effect of Molecular Hydrogen on Functional States of Erythrocytes in Rats with Simulated Chronic Heart Failure.

Molecular hydrogen has an anti-inflammatory and cardioprotective effect, which is associated with its antioxidant properties. Erythrocytes are subjected to oxidative stress in pathologies of the cardiovascular system, which is the cause of a violation of the gas transport function of blood and microcirculation. Therefore, our aim was to investigate the effects of H2 inhalation on the functional states of red blood cells (RBCs) in chronic heart failure (CHF) in rats. The markers of lipid peroxidation, antioxidant capacity, electrophoretic mobility of erythrocytes (EPM), aggregation, levels of adenosine triphosphate (ATP) and 2,3-diphosphoglyceric acid (2,3-DPG), hematological parameters were estimated in RBCs. An increase in EPM and a decrease in the level of aggregation were observed in groups with multiple and single H2 application. The orientation of lipoperoxidation processes in erythrocytes was combined with the dynamics of changes in oxidative processes in blood plasma, it was observed with both single and multiple exposures, although the severity of the changes was greater with multiple H2 inhalations. Probably, the antioxidant effects of molecular hydrogen mediate its metabolic action. Based on these data, we conclude the use of H2 improves microcirculation and oxygen transport function of blood and can be effective in the treatment of CHF.

Molecular hydrogen exposure improves functional state of red blood cells in the early postoperative period: a randomized clinical study.

Molecular hydrogen (H2) has been considered a preventive and therapeutic medical gas in numerous diseases. The study aimed to investigate the potential role of molecular hydrogen as a component of anesthesia in surgical treatment with cardiopulmonary bypass (CPB) of acquired valve defects on the functional state of red blood cells (RBC) and functional indicators of cardiac activity. This clinical trial was conducted with 20 patients referring to the Specialized Cardiosurgical Clinical Hospital, Nizhny Novgorod, Russian Federation, who underwent elective surgery with CPB. Twenty-four patients were randomly assigned to two groups. First group included 12 patients (research group) who received H2 at a concentration of 1.5-2.0% through a facemask using a breathing circuit of the ventilator together with anesthesia immediately after tracheal intubation and throughout the operation. Second group (control group) included 12 patients who were not given H2. Blood samples were withdrawn from peripheral veins and radial artery at four stages: immediately after the introduction of anesthesia (stage 1), before the start of CPB (stage 2), immediately after its termination (stage 3) and 24 hours after the operation (the early postoperative period) (stage 4). An increase in electrophoretic mobility, an increase in the metabolism of red blood cells, and a decrease in the aggregation of red blood cells relative to the corresponding indicators of the control group were observed in the research group. Patients in the research group had a decrease in oxidative stress manifestations most pronounced one day after the operation. There was a statistically significant difference between the indicators of myocardial contractile function in the research and control group on the 1st and 3rd days after surgery. H2 inhalation leads to improvement of functional state of red blood cells, which is accompanied by a more favorable course of the early postoperative period. These data show the presence of protective properties of molecular hydrogen.

Recent Advances in Manufacturing Innovative Stents.

Cardiovascular diseases are the most distributed cause of death worldwide. Stenting of arteries as a percutaneous transluminal angioplasty procedure became a promising minimally invasive therapy based on re-opening narrowed arteries by stent insertion. In order to improve and optimize this method, many research groups are focusing on designing new or improving existent stents. Since the beginning of the stent development in 1986, starting with bare-metal stents (BMS), these devices have been continuously enhanced by applying new materials, developing stent coatings based on inorganic and organic compounds including drugs, nanoparticles or biological components such as genes and cells, as well as adapting stent designs with different fabrication technologies. Drug eluting stents (DES) have been developed to overcome the main shortcomings of BMS or coated stents. Coatings are mainly applied to control biocompatibility, degradation rate, protein adsorption, and allow adequate endothelialization in order to ensure better clinical outcome of BMS, reducing restenosis and thrombosis. As coating materials (i) organic polymers: polyurethanes, poly(ε-caprolactone), styrene-b-isobutylene-b-styrene, polyhydroxybutyrates, poly(lactide-co-glycolide), and phosphoryl choline; (ii) biological components: vascular endothelial growth factor (VEGF) and anti-CD34 antibody and (iii) inorganic coatings: noble metals, wide class of oxides, nitrides, silicide and carbide, hydroxyapatite, diamond-like carbon, and others are used. DES were developed to reduce the tissue hyperplasia and in-stent restenosis utilizing antiproliferative substances like paclitaxel, limus (siro-, zotaro-, evero-, bio-, amphi-, tacro-limus), ABT-578, tyrphostin AGL-2043, genes, etc. The innovative solutions aim at overcoming the main limitations of the stent technology, such as in-stent restenosis and stent thrombosis, while maintaining the prime requirements on biocompatibility, biodegradability, and mechanical behavior. This paper provides an overview of the existing stent types, their functionality, materials, and manufacturing conditions demonstrating the still huge potential for the development of promising stent solutions.

Surface evaluation of titanium oxynitride coatings used for developing layered cardiovascular stents.

Stents are important medical devices used to increase the quality and life expectancy of patients with heart diseases and stroke, leading causes of death, worldwide. In order to minimize the risk of restenosis, different coating on bare metal stents (BMS) such as polymer coatings; titanium dioxide, titanium nitride or titanium oxynitride coatings; carbon coatings and others are used. The aim of this work was to develop novel stents coated with titanium oxynitride (TiOxNy) with optimal chemical, mechanical and biological properties having possibly good coverage rate of inner and outer stent surfaces. The improvement should be achieved by optimization and development of a magnetron sputtering deposition technology. The goal of the study is understanding of the existing potential for improvement of the deposition technology and the coating quality itself. For this study, different O2/N2 ratios, meaning 1/2, 1/5 and 1/10 (the ratios of reagent gasses are given for the values of mass flows into the chamber) has been selected. Stability in simulated body fluids, surface morphology and protein adsorption as well as preliminary cytotoxic behaviour of the samples on HUVEC cells has been analysed. SEM experiments have shown the potential in the improvement of coating-stent adhesion by all samples. TiOxNy 1:5 samples were found to have the lowest adsorption, the smoothest surface morphology and the smallest rate of salt deposition from simulated body fluids (SBFs). This kind of surface has been recommended for further optimization and application.

Nanoscale Electrical Potential and Roughness of a Calcium Phosphate Surface Promotes the Osteogenic Phenotype of Stromal Cells.

Mesenchymal stem cells (MSCs) and osteoblasts respond to the surface electrical charge and topography of biomaterials. This work focuses on the connection between the roughness of calcium phosphate (CP) surfaces and their electrical potential (EP) at the micro- and nanoscales and the possible role of these parameters in jointly affecting human MSC osteogenic differentiation and maturation in vitro. A microarc CP coating was deposited on titanium substrates and characterized at the micro- and nanoscale. Human adult adipose-derived MSCs (hAMSCs) or prenatal stromal cells from the human lung (HLPSCs) were cultured on the CP surface to estimate MSC behavior. The roughness, nonuniform charge polarity, and EP of CP microarc coatings on a titanium substrate were shown to affect the osteogenic differentiation and maturation of hAMSCs and HLPSCs in vitro. The surface EP induced by the negative charge increased with increasing surface roughness at the microscale. The surface relief at the nanoscale had an impact on the sign of the EP. Negative electrical charges were mainly located within the micro- and nanosockets of the coating surface, whereas positive charges were detected predominantly at the nanorelief peaks. HLPSCs located in the sockets of the CP surface expressed the osteoblastic markers osteocalcin and alkaline phosphatase. The CP multilevel topography induced charge polarity and an EP and overall promoted the osteoblast phenotype of HLPSCs. The negative sign of the EP and its magnitude at the micro- and nanosockets might be sensitive factors that can trigger osteoblastic differentiation and maturation of human stromal cells.

Rough Titanium Oxide Coating Prepared by Micro-Arc Oxidation Causes Down-Regulation of hTERT Expression, Molecular Presentation, and Cytokine Secretion in Tumor Jurkat T Cells.

The response of the human Jurkat T cell leukemia-derived cell line (Jurkat T cells) after 24 h of in vitro exposure to a titanium substrate (12 × 12 × 1 mm³) with a bilateral rough (Ra = 2.2-3.7 µm) titanium oxide coating (rTOC) applied using the micro-arc method in a 20% orthophosphoric acid solution was studied. A 1.5-fold down-regulation of hTERT mRNA expression and decreases in CD3, CD4, CD8, and CD95 presentation and IL-4 and TNFα secretion were observed. Jurkat T cell inactivation was not correlated with the generation of intracellular reactive oxygen species (ROS) and was not mediated by TiO2 nanoparticles with a diameter of 14 ± 8 nm at doses of 1 mg/L or 10 mg/L. The inhibitory effect of the rTOC (Ra = 2.2-3.7 µm) on the survival of Jurkat T cells (Spearman's coefficient rs = -0.95; n = 9; p < 0.0001) was demonstrated by an increase in the necrotic cell count among the cell population. In turn, an elevation of the Ra index of the rTOC was accompanied by a linear increase (r = 0.6; p < 0.000001, n = 60) in the magnitude of the negative electrostatic potential of the titanium oxide surface. Thus, the roughness of the rTOC induces an electrostatic potential and decreases the viability of the immortalized Jurkat T cells through mechanisms unrelated to ROS generation. This may be useful for replacement surgery applications of rough TiO2 implants in cancer patients.

Heart and Lungs Protection Technique for Cardiac Surgery with Cardiopulmonary Bypass.

INTRODUCTION: Cardioplegic cardiac arrest with subsequent ischemic-reperfusion injuries can lead to the development of inflammation of the myocardium, leucocyte activation, and release of cardiac enzymes. Flow reduction to the bronchial arteries, causing low-flow lung ischemia, leads to the development of a pulmonary regional inflammatory response. Hypoventilation during cardiopulmonary bypass (CPB) is responsible for development of microatelectasis, hydrostatic pulmonary edema, poor compliance, and a higher incidence of infection. Based on these facts, prevention methods of these complications were developed. The aim of this study was to evaluate constant coronary perfusion (CCP) and the "beating heart" in combination with pulmonary artery perfusion (PAP) and "ventilated lungs" technique for heart and lung protection in cardiac surgery with CPB. METHODS: After ethical approval and written informed consent, 80 patients undergoing cardiac surgery with normothermic CPB were randomized in three groups. In the first group (22 patients), the crystalloid cardioplegia without lung ventilation/perfusion techniques were used. In the second group (30 patients), the CCP and "beating heart" without lung ventilation/perfusion techniques were used. In the third group (28 patients), the CCP with PAP and lung ventilation techniques were used. Clinical, functional parameters, myocardial damage markers (CK MB level), oxygenation index, and lung compliance were investigated. RESULTS: There were higher rates of spontaneous cardiac recovery and lower doses of inotrops in the second and third groups. Myocardial contractility function was better preserved in the second and third groups. The post-operative levels of CK-MB were lower than in control group. Three hours after surgery CK-MB levels in the second and third groups were lower by 38.1% and 33.3%, respectively. Eight hours after surgery, CK-MB levels were lower in the second and third groups by 45.9% and 47.7%, respectively. 24 hours after surgery, CK-MB levels were lower in the second and third groups by 42.0% and 42.6%, respectively, and lower by 29.7% and 27.4% 48 hours after surgery, respectively. Normalization of CK-MB levels were registered earlier in second and third groups (within 24 hours) than the control group. Oxygenation index and lung compliance were significantly higher in the third group after CPB. CONCLUSION: Our technique improved myocardial and lung function in patients, but larger prospective randomized trials are needed to definitively assess the protective effects of this technique.