This study aims to determine the effectiveness of administering 80 ppm nitric oxide in reducing kidney injury, mitochondrial dysfunction and regulated cell death in kidneys during experimental perfusion. Twenty-four sheep were randomized into four groups: two groups received 80 ppm NO conditioning with 90 min of cardiopulmonary bypass (CPB + NO) or 90 min of CPB and hypothermic circulatory arrest (CPB + CA + NO), while two groups received sham protocols (CPB and CPB + CA). Kidney injury was assessed using laboratory (neutrophil gelatinase-associated lipocalin, an acute kidney injury biomarker) and morphological methods (morphometric histological changes in kidney biopsy specimens). A kidney biopsy was performed 60 min after weaning from mechanical perfusion. NO did not increase the concentrations of inhaled NO₂ and methemoglobin significantly. The NO-conditioning groups showed less severe kidney injury and mitochondrial dysfunction, with statistical significance in the CPB + NO group and reduced tumor necrosis factor-α expression as a trigger of apoptosis and necroptosis in renal tissue in the CPB + CA + NO group compared to the CPB + CA group. The severity of mitochondrial dysfunction in renal tissue was insignificantly lower in the NO-conditioning groups. We conclude that NO administration is safe and effective at reducing kidney injury, mitochondrial dysfunction and regulated cell death in kidneys during experimental CPB.

The article describes a clinical case of inhalation therapy with high doses of nitric oxide (NO) in a comorbid patient with a severe course of COVID-19. An air stream containing NO was generated using the PLAZON device. High-dose NO inhalation therapy was administered as a life-saving option due to the lack of effect from treatment delivered in accordance with the current national clinical guidelines for the treatment of COVID-19. The safety and clinical efficacy of the technique was demonstrated.

INTRODUCTION: Acute kidney injury is one of the common complications in cardiosurgical operations with cardiopulmonary bypass (CPB). A number of studies have shown that donation of exogenous nitric oxide (NO) reduces episodes of аcute kidney injury. However, subcellular mechanisms of realization the nephroprotective properties of NO remain unknown. OBJECTIVE: To study the safety of the technology of plasma-chemical synthesis of nitric oxide and to evaluate the effect of the delivery resulting nitric oxide on mitochondrial damage to the renal tissue in the simulation of cardiopulmonary bypass. MATERIALS AND METHODS: Experiment included 12 rams of the Altai breed. Animals were divided into 2 groups: 6 animals were modeled CPB; 6 animals were simulated CPB with NO delivery. Mitochondrial damage was assessed by calcium-binding capacity and transmembrane potential of mitochondria 1 h after weaning from the CPB. The safety of the NO delivery according to the proposed method was assessed by the concentration of nitrogen dioxide on inspiration, the level of methemoglobin. The efficiency of NO delivery according to the proposed method was assessed by the level of stable NO metabolites: endogenous nitrite, nitrate and total concentration of NO metabolites. RESULTS: In the group of animals with NO delivery the average level of transmembrane potential of mitochondria was (171.66 ± 20.41 vs 126.66 ± 18.61; p = 0.00256) and calcium-binding capacity of mitochondria was (1466.66 ± 216.02 vs 866.66 ± 216.02; p = 0.000712) of renal parenchyma. Methemoglobin levels above the recommended thresholds in clinical practice were not recorded in the CPB+NO group. The values of total concentration of NO metabolites and nitrate in the CPB+NO group compared to the CPB group are statistically significantly higher, p = 0.00006; p = 0.0035, respectively. CONCLUSIONS: Plasma-chemical synthesis of nitric oxide is a safe technology, and the use of the resulting nitric oxide in cardiopulmonary bypass leads to a decrease in the severity of mitochondrial dysfunction in the kidney parenchyma.

The objective was to study the effect of the delivery of exogenous nitric oxide on the severity of apoptosis, pyroptosis, and necroptosis of the renal parenchyma after simulating cardiopulmonary bypass and cardiopulmonary bypass with circulatory arrest.Materials and Methods. 24 Altai breed rams were randomized into 4 equal groups. In the CPB and CPB+NO groups, we simulated cardiopulmonary bypass without circulatory arrest. In the CPB+CA and CPB+CA+NO groups, we simulated cardiopulmonary bypass with circulatory arrest. In the CPB+NO, CPB+CA+NO groups, NO was given perioperative in concentration of 80 ppm. In the CPB, CPB+CA groups, we supplied a standard oxygen-air mixture without NO.Results. In the CPB+CA+NO group, the TNF-α concentration was statistically significantly lower: 899 [739; 1019] ng/g compared to the CPB+CA group 1716 [1284; 2201] ng/g, p = 0.026. The remaining markers of programmed cell death did not differ between groups.Conclusions. Perioperative nitric oxide delivery reduces the expression of the extrinsic pathway of apoptosis of renal parenchyma cells in simulating operations with artificial circulation and circulatory arrest. Perioperative nitric oxide delivery at a dose of 80 ppm does not increase the processes of apoptosis, pyroptosis, and necroptosis in renal parenchyma.

Introduction: Organoprotective effects of perioperative nitric oxide delivery towards the heart and kidneys have been demonstrated many times in cardiac surgery but information about its ability to prevent respiratory complications is extremely limited. Objective: This study aimed at evaluation of the efficacy and the safety of perioperative nitric oxide delivery for preventing respiratory complications during cardiac surgeries involving cardiopulmonary bypass in patients with an increased risk of adverse respiratory events and the identification of the risk factors towards postoperative acute respiratory. Methods: A prospective randomised controlled study included 132 cardiac surgical patients with increased risk of postoperative respiratory failure who were divided into two groups. The main group received nitric oxide at a concentration of 80 ppm throughout the operation and the first 6 hours at the postoperative period. The primary endpoint was the ratio of the partial pressure of oxygen in arterial blood to the fraction of inspired oxygen in 24 hours after the operation. Results: Patients receiving perioperative nitric oxide demonstrated significant improvements in oxygenation (paO2/FiO2 ratio, p < 0.001) in 24 hour post-surgery period that was associated with a decrease in pulmonary shunt fraction (p < 0.001), a decline of acute respiratory failure incidence (p = 0.042), and postoperative pneumonia (p = 0.013). Delivery of nitric oxide did not entail an increase in methemoglobin concentration above 5% and nitrogen dioxide above 3 ppm. In 24 h after surgery, revealed cases of acute respiratory failure were associated with blood transfusion (p = 0.033), as well as an excess of cardiopulmonary bypass duration of more than 97 min and mechanical ventilator duration of more than 628 min. Conclusion: Perioperative delivery of 80 ppm nitric oxide in cardiac surgeries involving cardiopulmonary bypass is safe and effective since it results in improved pulmonary oxygenating function and decreased pulmonary complications. In patients with an increased risk of adverse respiratory events, identified risk factors of acute respiratory failure include blood transfusion, prolonged cardiopulmonary bypass, and extended mechanical ventilation. Received 23 September 2024. Revised 2 October 2024. Accepted 7 October 2024. FundingThe study was carried out within the framework of the state assignment under the topic of basic scientific research No. 122123000017-3. Conflict of interestsThe authors declare no conflict of interest. Contribution of the authorsConception and study design: N.O. Kamenshchikov, I.V. Kravchenko, Yu.K. Podoksenov, B.N. KozlovData collection and analysis: I.V. Kravchenko, M.A. Tyo, E.A. Churilina, M.S. Kozulin, A.M. Gusakova, T.P. KalashnikovaStatistical analysis: I.V. Kravchenko, Yu.K. PodoksenovDrafting the article: I.V. Kravchenko, Yu.K. PodoksenovCritical revision of the article: N.O. Kamenshchikov, B.N. KozlovFinal approval of the version to be published: I.V. Kravchenko, Yu.K. Podoksenov, M.A. Tyo, T.P. Kalashnikova, E.A. Churilina, M.S. Kozulin, A.M. Gusakova, B.N. Kozlov, N.O. Kamenshchikov

INTRODUCTION: Acute kidney injury (AKI) is a common and serious complication after cardiac surgery performed under cardiopulmonary bypass (CPB). Patients with chronic kidney disease (CKD) are particularly vulnerable to cardiac surgery-associated AKI. Nitric oxide (NO) has great potential for implementing multi-organ protection in cardiac surgery. OBJECTIVES: To test the hypothesis that perioperative nitric oxide conditioning has a good safety profile and reduces the incidence of acute kidney injury during cardiac surgery under cardiopulmonary bypass in patients with chronic kidney disease. MATERIAL AND METHODS: An interim analysis of the results of the single-center prospective randomized controlled trial DEFENDER was conducted. Currently, the study included 96 patients with CKD who underwent cardiac surgery under CPB. Patients was randomized into 2 equal groups consisting of 48 people each. In the experimental group, during the operation and 6 hours after it, 80 ppm NO was delivered through the ventilator and CPB circuits. In the control group, during the operation and 6 hours after it, a standard oxygen-air mixture without NO was delivered through the ventilator and CPB circuits. The end points of the study were: the difference between groups in the incidence of AKI, the incidence of postoperative complications, outcomes and the safety profile of NO therapy. RESULTS: In the experimental group, the incidence of AKI was significantly lower compared to the control group (16,7 и 35,4 %, p = 0.036). In the experimental group, nitrogen dioxide concentration in the gas-air mixture and methemoglobin level were not above the reference range. The groups did not differ in the frequency of blood transfusions, the amount of postoperative bleeding, or the number of platelets on the first day after surgery. CONCLUSIONS: Perioperative nitric oxide conditioning has a good safety profile and reduces the incidence of acute kidney injury during cardiac surgery with CPB in patients with chronic kidney disease.