Objective. To evaluate the effect of NO added to the sweep gas of the oxygenator during cardiopulmonary bypass (CPB) on the liver and kidneys in pigs. Methods. An experiment was carried out on 10 pigs undergoing cardiac surgery using CPB. NO was added to the sweep gas of the oxygenator at a concentration of 100 ppm for the animals in the experimental group (CPB-NO, n = 5). Animals in the control group (CPB-contr, n = 5) did not receive NO in the sweep gas of the oxygenator. The CPB lasted 4 h, followed by postoperative monitoring for 12 h. To assess the injury to the liver and kidneys, the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin, creatinine, and neutrophil gelatinase-associated lipocalin (NGAL) were determined initially, at weaning from the CPB, and 6 and 12 h after weaning from the CPB. The glomerular filtration rate (GFR) was evaluated initially, at weaning from the CPB, and 6 and 12 h after weaning from the CPB. A pathomorphological study of the liver and kidneys was performed using semiquantitative morphometry. Results. The long four-hour period of CPB deliberately used in our experiment caused liver and kidney injury. In the CPB-contr group, an increase in the ALT concentration was found: 43 (34; 44) U/L at baseline to 82 (53; 99) U/L 12 h after CPB, p < 0.05. The AST concentration in the CPB-contr group increased from 25 (17; 26) U/L at baseline to 269 (164; 376) U/L 12 h after CPB, p < 0.05. We found no significant increase in the ALT and AST concentrations in the CPB-NO group. There were no significant differences in ALT and AST concentrations between the CPB-NO and CPB-contr groups at all the study time-points. In the CPB-contr group, an increase in the creatinine level was found from 131 (129; 133) µmol/L at baseline to 273 (241; 306) µmol/L 12 h after CPB, p < 0.05. We found no significant increase in creatinine level in the CPB-NO group. Creatinine levels in the CPB-NO group were significantly lower than in the CPB-contr group 12 h after weaning from CPB: 183 (168; 196) vs. 273 (241; 306) µmol/L; p = 0.008. The GFR in the CPB-NO group was significantly higher than in the CPB-contr group 6 h after weaning from CPB: 78.9 (77.8; 82.3) vs. 67.9 (62.3; 69.2) mL/min; p = 0.016. GFR was significantly higher in the CPB-NO group than in the CPB-contr group 12 h after weaning from CPB: 67.7 (65.5; 68.0) vs. 50.3 (48.7; 54.9) mL/min; p = 0.032. We found no significant differences between the study groups in the level of NGAL. We found several differences between the groups in the pathomorphological study. Conclusions. NO added to the sweep gas of the oxygenator reduces creatinine levels and increases GFR during prolonged CPB injury. Further research is required.

Pharmacological scores, such as inotropic score (IS) and vasoactive-inotropic score (VIS) were created to quantify doses of vasoactive and inotropic drugs. The number of studies where IS and VIS were used for evaluation of postoperative period of adult patients after cardiac surgery is small. Objective: to estimate IS and VIS as an approach for monitoring of the hemodynamic profile and clinical outcomes in the early postoperative period of cardiac surgery. Methods. The study involved 144 patients older than 18 years who underwent cardiac surgery under cardiopulmonary bypass (CPB). In perioperative period we measured cardiac output using a Swan-Ganz catheter with the calculation of central hemodynamic parameters, and also VIS and IS wcre calculated. We evaluated the prognostic value of these pharmacological scores in the development of complications of the early postoperative period, as well as their correlation with the duration of respiratory support, the length of stay in the ICU, and total hospital time. Results. IS ≥ 10 significantly associated with prolonged respiratory support, a long stay in the ICU and with a mortality rate of 28.6 %. Patients with IS ≥ 10 are characterized by a violation of tissue perfusion, main cause of which may be a low cardiac output syndrome. IS ≥ 10 can be used as criteria for the low cardiac output syndrome with impaired organ perfusion. The use of this pharmacological score as a predictor of adverse clinical outcomes and increased mortality is justified. The hemodynamic profile of patients with VIS ≥ 10 is characterized by the absence of signs of cardiac output decrease and normal organ perfusion. It has low prognostic significance for the adverse postoperative clinical outcomes and should not be used as perioperative criteria for low cardiac output. In addition, VIS ≥ 10 requires careful use as a predictor of adverse postoperative outcomes and mortality.

To evaluate the effect of NO added to the oxygenator during CPB on the liver and kidneys in pigs.Methods. The experiment was conducted on 10 pigs undergoing cardiac surgery using cardiopulmonary bypass (CPB). Animals of the experimental group (CPB-NO; n = 5) received NO with the gas mixture supplied to the oxygenator at 100 ppm. Animals of the control group (CPB-control; n = 5) did not receive NO via the oxygenator. The surgery lasted 4 hours and was followed by 12-hour postoperative monitoring. To assess the liver and kidney injury, the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin, creatinine, neutrophil gelatinase-associated lipocalin (NGAL) were determined at baseline, at weaning from the CPB, 6 and 12 hours after weaning from the CPB. A pathomorphological study of the liver and kidneys was also performed.Results. A long period of CPB deliberately used in our experiment caused liver injury. In the CPB-control group, an increase in the ALT concentration was found: 43 (34; 44) U/l at baseline to 82 (53; 99) U/l 12 hours after CPB, p < 0.05. AST concentration in the CPB-control group increased from 25 (17; 26) U/l at baseline to 269 (164; 376) U/l 12 hours after CPB (p < 0.05). We found no significant increase in ALT and AST concentrations in the CPB-NO group. There were no significant differences in ALT and AST concentrations between CPB-NO and CPB-control groups at all study time points. In the CPB-control group, an increase in the creatinine level was found from 131 (129; 133) μmol/l at baseline to 273 (241; 306) μmol/l 12 hours after CPB (p < 0.05). We found no significant increase in creatinine levels in the CPB-NO group. Creatinine levels in the CPB-NO group were significantly lower than in the CPB-control group 12 h after weaning from CPB: 183 (168; 196) vs 273 (241; 306) μmol/l (p < 0.008). We found no significant differences between the study groups by the NGAL level. Morphology revealed characteristic alterative changes in tissues, circulatory disorders, and inflammatory infiltration of varying degrees of severity, which in combination is a manifestation of the acute damaging effect of CPB. In the CPB-NO group, the severity of pathological changes, measured in points, was lower than in the CPB-control group, but no statistically significant differences were found.Conclusion. NO added to the oxygenator gas mixture reduces liver and kidney injury during prolonged CPB. Further research is required.

Objective: The study aimed to review the literature data on the recommended maximum concentrations of nitrogen dioxide during inhaled therapy with nitric oxide and to propose a general list of recommendations on safe therapy with inhaled nitric oxide. Methods: The systematic review was performed according to the PRISMA 2020 criteria. A search was carried out in databases Russian Science Citation Index, MedLine, Cochrane Library using the keywords “nitrogen dioxide”, “limit concentration”, “annual limit value”, “inhaled nitric oxide”. Results: The review included 28 articles, 20 sources from regulatory authorities setting hygiene standards, and 2 instructions for devices. Conclusion: For short periods of NO inhalation not exceeding one hour, the maximum permissible concentration of NO2 in the inhaled gas mixture may be defined as 5 ppm. In cases of NO inhalation not exceeding 24 hours, the maximum permissible concentration of NO2 in the inhaled mixture should be considered as 2 ppm. If the duration of NO inhalation exceeds 24 hours, the permissible concentration of NO2 in the inhaled gas mixture should be limited to 1 ppm. Received 29 November 2024. Revised 9 January 2025. Accepted 13 January 2025. FundingThis research was carried out within the state assignment “Development of a new device for supplying nitric oxide synthesized from atmospheric air into mechanical circulatory assist devices” No. 123021000129‑1. Conflict of interestThe authors declare no conflict of interest. Contribution of the authorsConception and study design: A.E. Bautin, A.A. Burov, Yu.V. ValuevaData collection and analysis: I.G. Chomakhashvili, K.Yu. Afanasyeva, D.A. Kozyrev, E.K. Barygin, G.N. Ablesimov, N.V. Badalyan, M.S. Zhuravleva, A.M. Pozhidaeva, A.A. Burov, Yu.V. ValuevaDrafting the article: I.G. Chomakhashvili, A.A. Burov, Yu.V. ValuevaCritical revision of the article: A.E. Bautin, A.O. Marichev, A.M. Radovskiy, A.A. BurovFinal approval of the version to be published: A.E. Bautin, I.G. Chomakhashvili, K.Yu. Afanasyeva, A.O. Marichev, A.M. Radovskiy, D.A. Kozyrev, E.K. Barygin, G.N. Ablesimov, N.V. Badalyan, M.S. Zhuravleva, A.M. Pozhidaeva, A.A. Burov, Yu.V. Valueva

INTRODUCTION: Plasma cell-free hemoglobin (Hbf) has a negative effect on the results of cardiac surgery. OBJECTIVE: Analysis of the dynamics of the Hbf during cardiosurgical operations with CPB. Identification of the main factors for increasing the Hbf. MATERIALS AND METHODS: A prospective, single-center, cohort study included 50 patients who underwent cardiac surgery with CPB. Hbf was monitored before surgery, during CPB (10 minutes after the start, then every 30 minutes) and every 6 hours for two days. RESULTS: An increase in Hbf levels was found in 90 % of surgical procedure. In 8 % of cases, hemolysis was mild (0.1 < Hbf ≤ 0.4 g/l), in 48 % — moderate (0.4 < Hbf < 1 g/l), severe (Hbf ≥ 1 g/l) was after 34 % of operations. After weaning from CPB Hbf rapidly decreases and after 12 hours drop to the preoperative level. Aortic cross-clamping is a risk factor with an odds ratio of 1.038 (p = 0.036). A positive correlation was established between the Hbf level and the duration of CPB (r = 0.76; p < 0.001). In ROC-analysis, a good predictive ability for development of severe hemolysis was demonstrated by the time of CPB: AUC 0.74 (p = 0.014) with a threshold value of 76 minutes. During CABG, severe hemolysis developed significantly less frequently than during valve corrections — 12.5 % versus 44.1 %, p = 0.026. Hbf content was significantly lower with an initial hemoglobin concentration < 140 g/l than in patients with an initial hemoglobin level ≥ 140 g/l — 0.7 (0.5; 0.95) g/l versus 0.9 (0.7; 1.28) g/l, p = 0.036. CONCLUSIONS: Hemolysis is typical for the cardiac surgeries with CPB. The time of aoral clamping and CPB, the type of surgcry, the hemoglobin content before surgcry have an impact on the severity of hemolysis.

BACKGROUND Toxic effects of nitric dioxide (NO₂) released under nitric oxide (NO) inhalation limit the application of nitric oxide high-dose therapy of clinical conditions accompanied by increased pulmonary vascular resistance. OBJECTIVE To identify the combinations of safe NO and O₂ concentrations in inhaled gas compound for nitric dioxide release in a model of NO insufflation through the «Tianox» apparatus into respiratory circuit. MATERIAL AND METHODS The study was performed on an experimental model. There were 360 measurements of NO₂ content in 72 various combinations of NO and O_2. RESULTS NO₂ release depended on NO and O₂ content in gas mixture. Multivariate regression analysis confirmed this fact. NO₂ concentration <2 ppm was recognized as a safe value. ROC-analysis confirmed predictive ability of NO and O₂ regarding toxic NO₂ concentrations. In case of inhalation therapy through the «Tianox» apparatus with any NO concentrations (10—80 ppm), O₂ content in gas mixture within 21—30% was safe. NO concentration <50 ppm is safe at any O₂ content in gas mixture (21—100%). CONCLUSION There is a fundamentally new source of NO in the Tianox device (synthesis from atmospheric air). We obtained data on possible safe combinations of inhaled O2 and NO regarding NO₂ release for effective clinical use of this device.