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.

The study included 90 patients who underwent heart valve surgery and combined procedures under CPB and pharmacological cardioplegia. Three groups were created: group 1 (control, n=30); group 2 (n=30) — NO inhalation (20 ppm) was conducted traditionally, that is, before and after CPB; group 3 (n=30) — NO inhalation was performed using a new technology — during the entire operation, with pulmonary artery perfusion and lung ventilation performed during CPB. Troponin I (cTn I) level, changes in the pulmonary function parameters, and clinical indicators were studied. Statistically significant lower levels of postoperative cTn I were registered in the patients of groups 2 and 3, at the same time, the levels were significantly lower in group 3 compared to group 2. The patients in group 1 (standardized anesthesia protocol) demonstrated an increase in the alveolar-arterial oxygen difference, an increase in intrapulmonary shunting, a decrease in blood oxygenation, and static lung compliance after СРВ. In both cases, NO inhalation retained the values of lung compliance and pulmonary oxygenating function after CPB, and in the patients of group 3, it also significantly reduced intrapulmonary shunting and alveolar-arterial difference after CPB. NO inhalation allowed a statistically significant decrease in the incidence of pulmonary dysfunction, acute respiratory failure, as well as the time of respiratory support in the ICU. The developed technology for the use of inhaled NO in surgery with CPB provides a clinically marked protective effect on the heart and lungs. The effectiveness of the protective action of NO depends on the duration of its administration and is most pronounced when used during the entire operation, including CPB time.

Objectives. To study the clinical efficacy and safety of using the method of synthesis of nitric oxide (NO) from atmospheric air in the postoperative period of cardiac surgery in children with precapillary pulmonary hypertension (PH). Materials and methods. A clinical study with retrospective control included 90 patients (28 newborns and 62 children older than 28 days), including 40 boys and 50 girls, median age 0.25 (0.28; 1.17) years. The following inclusion criteria were determined: signed informed consent of the patientʼs legal representative, underwent heart surgery, mechanical controlled ventilation (MCV), pulmonary artery systolic pressure (PAPsys) ≥ 35 mm Hg. Exclusion criteria: methemoglobinemia, left ventricular failure III — IV, hemorrhagic diathesis. 45 children were included in the study group (inhalation of NO obtained by synthesis from atmospheric air using the AIT-NO-01 device), 45 children were included in the retrospective control group (application of the NO delivery method from cylinders, NOXBOX Mobile device (Bedfont, UK)). There were no differences in anthropometric parameters and severity of baseline precapillary PH between the groups. Results. After one hour of NO inhalation using the AIT-NO-01, a decrease in PAPsys was noted. by 33.3 % (p < 0.001). In the retrospective control group, after one hour of NO inhalation, there was a decrease in PAPsys by 26.7 % (p < 0.001). PAPsys decreased by 10 % or more in 40 (89 %) of patients in the study group and in 38 (84 %) of patients in the retrospective control group, (p = 0.4). Inhalation of NO obtained by the synthesis method from atmospheric air was associated with a shorter duration of MCV compared with the method of supply from cylinders: 12 (2; 28) h versus 14 (12.2; 70.5) h, p = 0.01. The length of ICU stay and postoperative complications rate did not differ in the study groups. There were no differences in the risk and severity of the side effects of NO inhalation therapy (the synthesis of methemoglobin and NO2) between the two methods studied. Conclusion. NO inhalation therapy after cardiac surgery in children using the AIT-NO-01 device has the same effectiveness and safety compared with the method of NO supply from cylinders.

The study included 91 patients who underwent heart surgery under CPB. The patients were randomized into 3 groups: group 1 comprised 30 patients (control); group 2 consisted of 33 patients with an isolated supply of nitric oxide (40 ppm) to the extracorporeal circuit; group 3 included 28 patients with a combined supply of nitric oxide (40 ppm) and hydrogen (1.2 ppm) into the extracorporeal circuit. The intensity of lipid peroxidation processes was studied by the content of diene conjugates (DC), triene conjugates (TC), Schiff bases (SB) in blood plasma; erythrocyte aggregation was also examined. The studies were carried out at the following stages: stage 1 (initial) — after induction of anesthesia; stage 2 — before CPB; stage 3 — 5 min after CPB initiation; stage 4 — at the 30^th minute of CPB; stage 5 — at the 60^th minute of CPB; stage 6 — at the 90^th minute of CPB; stage 7 — at CPB termination; stage 8 — at the end of the operation. The content of DC increased statistically significantly at the 90^th minute of CPB to 1.093±0.573 rel. units (M±SD) in patients of group 1; to 0.322±0.047 rel. units in group 2; to 0.287±0.003 rel. units in group 3, while the DC content was statistically significantly lower in patients of groups 2 and 3 compared to group 1. A statistically significant increase in the content of TC compared to the initial value was observed at the 90^th minute of CPB in group 1 (up to 0.334±0.114 rel. units), while the content of TC was statistically significantly lower in patients of groups 2 and 3. A statistically significant growth in the content of SB occurred at the 90^th minute of CPB in patients of group 1 up to 33.324±15.640 rel. units. This indicator was statistically significantly lower in groups 2 and 3 relative to the patients of group 1. The dynamics of erythrocyte aggregation in patients of group 1 showed statistically significant growth of this indicator from the start of CPB to the end of the operation (from 44.8±1.4 to 73.1±2.2%). The statistically significant difference from the indicator at the beginning of the operation started at the 30^th minute of CPB and lasted until the end of the operation. In patients of group 2, it decreased statistically significantly during CPB (from 56.5±2.3% before the CPB initiation to 47.4±1.2% at the CPB termination); in patients of group 3, it was decreasing from the 60^th minute of CPB to the end of the operation and was statistically significantly lower than in patients of both groups 1 and 2. No postoperative complications were noted (acute heart failure, acute respiratory failure, multiple organ failure) in patients of groups 2 and 3. A statistically significant decrease in both the duration of mechanical ventilation and stay in the intensive care unit was registered in group 3 compared to group 2. The combined use of gaseous nitric oxide and hydrogen during CPB allowed a statistically significant decrease in the level of activation of lipid peroxidation and erythrocyte aggregation, which ensured a higher level of organ protection during cardiac surgery, faster activation of patients, and a shorter stay in the intensive care unit.

Introduction. Usually, gaseous nitric oxide (NO) is supplied to the patient by inhalation, adding to the inhaled gas mixture during spontaneous breathing, or supplying it to the inspiratory part of the ventilator. It is believed that the main point of its action is the pulmonary vasculature, where it exhibits an expanding effect, thus improving the oxygenation of arterial blood and reducing the pulmonary artery pressure. However, data from recent experimental clinical studies suggest that the addition of NO directly to the gas mixture supplied to the oxygenator makes it possible to systemically deliver NO into the bloodstream and, thereby, reduce the inflammatory response of the whole body caused by the extracorporeal circuit (cardiopulmonary bypass [CPB] or extracorporeal membrane oxygenation [ECMO]). Materials and methods. The search for publications was carried out in electronic databases PubMed, EMBASE. The last search term was December 30, 2020. The search term included the following words: “nitric oxide” and “artificial circulation” or “ECMO”. Only experimental and clinical randomized controlled blinded studies were selected for inclusion in the review. Results. The article analyzes data from recent studies related to the delivery of gaseous NO to the extracorporeal circuit, among which the issues of both NO delivery into the cardiopulmonary bypass line and the systemic and organ effects of nitric oxide delivered to the circuit are considered. The cardioprotective and anti-inflammatory effects of NO supplied to the extracorporeal circulation are considered in detail, as well as its effect on the lungs and kidneys. Conclusions. Further new randomized trials are needed to determine the place of the technology for supplying gaseous nitric oxide to the line of heart-lung machines or ECMO in modern cardiac surgery.

The aim of the study was to evaluate the impact of various technologies for the use of gaseous nitric oxide on the state of the lungs and heart during heart valve surgery under cardiopulmonary bypass (CPB).Methods. The study included 93 patients of both sexes. All patients underwent heart valve surgery and combined surgical interventions under CPB. The patients were divided into 4 groups. Group 1 (control, n = 30) used the standard protocol for anesthetic and perfusion management. Group 2 (n = 30) received inhalation of nitric oxide (20 ppm) within 3 days before surgery, as well as before and after CPB. Group 3 (n = 30) inhaled nitric oxide (40 ppm) throughout surgery with the medication delivered through inspiratory part of the ventilator and combined with perfusion of the pulmonary artery and reduced volume ventilation during CPB. Group 4 (n = 33) received nitric oxide (40 ppm) via oxygenator of the heart-lung machine. We assessed changes in the functional parameters of the lungs at different phases of surgery, performed a morphological examination of the lungs in the initial phase (before CPB), at the peak of ischemia, and after reperfusion. The state of the myocardium after surgery was assessed by troponin I (cTnI) activity at the beginning of the operation, after transfer to the ICU, at 12, 24 and 48 hours after the surgery. Myocardial damage index (MDI) was calculated according to the following formula: MDI = TnIlate / TnIearly. The clinical outcomes of the surgeries were evaluated.Results. There were no statistically significant differences in the functional state of the lungs with various options for inhalation delivery and administration via the CPB circuit. The most intact indicators of the functional state of the lungs were seen in patients of Group 3 who received inhaled nitric oxide throughout surgery and combined mechanical ventilation with the addition of nitric oxide and perfusion of the pulmonary artery during CPB. Morphological examination of the lungs showed that inhalation of nitric oxide before CPB does not prevent the development of morphological disorders. Morphological changes found in Group 3 were the smallest. The supply of nitric oxide into the CPB circuit statistically significantly improved the restoration of pulmonary blood flow during reperfusion. The cTnI level statistically significantly increased in all groups of patients, however, it was statistically significantly lower in Groups 2, 3, and 4 compared with Group 1 at the end of surgery, in Groups 3 and 4 compared with Groups 1 and 2 after 12 and 24 hours, and in Group 3 after 48 hours. The most favorable changes in the MDI were seen in Group 3; statistically significantly lower MDI was registered 12 and 48 hours after surgery in this group compared with Groups 1, 2, and 4. A lower complication rate, a shorter duration of ventilation and stay in the ICU were observed in Groups 3 and 4.Conclusion. Nitric oxide has a protective effect on the lungs and heart when used during anesthesia and cardiopulmonary bypass in heart valve surgery. It preserves the lung function and morphology and statistically significantly reduces cTnI level and myocardial damage index in the postoperative period. The extent of the protective effect depends on the nitric oxide exposure time and is most pronounced when nitric oxide is used throughout the surgery, including during CPB.