Aim. To study the prevalence and risk factors (RF) for hospital-acquired pneumonia (HAP) after on-pump cardiac surgery in a modern cohort of patients.Material and methods. This retrospective analysis of the medical records of cardiovascular surgery patients, operated on in the period from January 1, 2022 to December 31, 2022. The study consistently included 417 patients who underwent on-pump cardiac surgery. The incidence and timing of HAP development were assessed. The influence of the main demographic, clinical, and perioperative factors on HAP risk was studied.Results. The pneumonia prevalence per year was 27,6%, including after the Frozen Elephant Trunk (FET) procedure — 32%, after coronary artery bypass grafting (CABG) — 29,5%, after combined CABG and heart valve surgery — 26,2%, after isolated valve surgery — 25,9%, after thoracic aortic hemiarch replacement — 19,5%. Pneumonia developed on the 4,6±2,9 day after surgery. The risk of pneumonia increased with atrial fibrillation (AF) before surgery (odds ratio (OR) 3,17; 95% confidence interval (CI): 1,67; 6,02, p=0,0002), on-pump duration (OR 1,01; 95% CI: 1,00; 1,01; p=0,0006), aortic cross-clamping (OR 1,01; 95% CI: 1,00; 1,01; p=0,0002) and mechanical ventilation (OR 1,03; 95% CI: 1,01; 1,05; p=0,005). Pneumonia predictors were on-pump duration ≥96 min (sensitivity 67,7%, specificity 64,6%, AUC=0,681, p=0,0006) and mechanical ventilation ≥14 h (sensitivity 63,1%, specificity 69,3%, AUC=0,641, p=0,005), as well as preoperative AF (sensitivity 61%, specificity 75%, p=0,0002).Conclusion. Preoperative AF, on-pump duration ≥96 min and mechanical ventilation ≥14 h serve as categorical and quantitative predictors of postoperative HAP in a modern cohort of patients.

Background and Aims:Cardiopulmonary bypass (CPB) and circulatory arrest (CA) can induce intestinal injury and consequently lead to multiple organ dysfunction. Nitric oxide (NO) has protective effects, but its effect on the intestine has not been studied. The study aimed to investigate intestinal injury variables and prove the intestinal protective effects of exogenous nitric oxide when modelling CPB and CA in an experiment. Methods:The study was performed on sheep (n = 24). There were four groups: CPB, CPB + NO, CPB + CA and CPB + CA + NO. Sheep in NO groups received intraoperative inhalation of NO at a dose of 80 ppm. Groups without NO underwent CPB and CA without NO delivery. Defaecation rate, dynamics of intestinal fatty acid binding protein (i-FABP), coefficient of microviscosity and polarity in the areas of lipid-lipid and protein-lipid interactions of erythrocyte membranes were assessed. One hour after CPB, the intestinal tissue was collected and assessed for tissue concentrations of adenosine triphosphate (ATP) and lactate. Results:The defaecation rate after CPB was higher in the CPB + NO group than in the CPB group. The concentration of i-FABP after CPB was lower in the CPB + NO and CPB + CA + NO groups than in the CPB and CPB + CA groups. Erythrocyte deformability before and after CPB revealed no significant dynamics in groups with NO. The ATP concentration 1 h after CPB was higher in the CPB + NO group than in the CPB group. The morphological picture in groups with NO was better. Conclusion:When modelling CPB and CA, NO had a positive effect on the functional and structural state of the intestine and also maintained erythrocyte deformability.

Myocardial revascularization has been known to not affect the prognosis in some patients. Coronary artery bypass graft (CABG) failure may develop one year after CABG surgery. This is accompanied by a high risk of developing myocardial infarction after complete myocardial revascularization in obstructive coronary artery disease (CAD) due to microvascular dysfunction. The study of microvascular dysfunction using intraoperative stress tests with adenosine triphosphate (ATP) allows for the assessment of the coronary bypass flow reserve (CBFR) and the risk of graft failure one year after surgery. The study included 79 CAD patients (238 grafts) who underwent dynamic single-photon emission computed tomography (SPECT) before CABG and dynamic transit time flow measurement (TTFM) during CABG at rest and at stress. The CBFR was calculated by the ratio of the mean graft flow (MGF) at stress to the MGF at rest. A multivariate regression model showed that the MGF at rest (p = 0.043), the MGF at stress (p = 0.026) and the CBFR (p = 0.0001) were significant independent predictors of graft failure. As a result of ROC analysis, the threshold CBFR < 1.67 units correlated with graft failure more closely (sensitivity 82%, specificity 90%) The CBFR is a significant independent predictor of graft failure for up to 16 months.

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

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.

Perioperative management of cardiac surgery leads to significant morphofunctional impairment of the lungs, cardiopulmonary bypass (CPB) being the principal contributor. The pathophysiological mechanisms associated with cardiopulmonary bypass include ischaemic-reperfusion injury, oxidative stress and systemic inflammation. Nitric oxide is able to limit the associated damage. Aim of the study: to investigate the effect of nitric oxide supply on morphofunctional state of sheep lungs under simulated cardiopulmonary bypass. Methods. 12 sheep of Altai breed were divided into 2 equal groups. Classical techniques of pulmonary ventilation and cardiopulmonary bypass were simulated in the CPB group. The sheep of the CPB + NO group were supplied with 80 ppm nitric oxide (via respiratory circuit or extracorporeal circulation circuit) during mechanical ventilation and cardiopulmonary bypass. The gas supply started immediately after tracheal intubation and continued until the end of the experiment. In both groups, the cardiopulmonary bypass time was 90 min, after which the sheep were switched to spontaneous circulation and observed for 60 min. Subsequently, blood was sampled, and the animals were withdrawn from the experiment with subsequent collection of histologic specimens. Results . Statistically significant intergroup differences in P / F-index level before the end of the experiment were found (p = 0.041). Nitric oxide supply was associated with decreased infiltrate density in the lung parenchyma (p = 0.006) and increased alveolar area (p < 0.001). Conclusion . Supply of NO during modelling of cardiopulmonary bypass in experimental animals improves the morphological and functional state of the lungs by reducing inflammation, vascular changes and damage to the respiratory part of the lungs (structure of alveoli, alveolar passages and pneumocytes). Clinical studies are needed to investigate pulmonoprotective properties of NO in humans.

BACKGROUND:Inhaled nitric oxide (iNO) showed to improve oxygenation at low doses by reducing intrapulmonary shunt and to display antiviral properties at high doses. To assess the safety and potential benefits, we designed an exploratory clinical trial comparing low-dose with intermittent high-dose iNO to only intermittent high-dose iNO in hypoxemic COVID-19 patients. METHODS:In this single-center interventional non-inferiority randomized trial (ClinicalTrials.gov, NCT04476992), twenty oxygen-dependent COVID-19 patients were randomly assigned to the high-dose (200 ppm for 30 min) + continuous low-dose (20 ppm) iNO group (iNO200/20) or the high-dose iNO group (iNO200). Methemoglobinemia (MetHb) assessed 48 h after iNO initiation was the primary endpoint. Reverse-transcription polymerase chain reaction for SARS-CoV-2, inflammatory markers during hospitalization, and heart ultrasounds during the iNO200 treatments were evaluated. RESULTS:MetHb difference between iNO groups remained within the non-inferiority limit of 3 %, indicating comparable treatments despite being statistically different (p-value<0.01). Both groups presented similar SpO2/FiO2 ratio at 48 h (iNO200 vs. iNO200/20 341[334-356] vs. 359 [331-380], respectively, p-value = 0.436). Both groups showed the same time to SARS-CoV-2 negativization, hospital length of stay, and recovery time. iNO-treated patients showed quicker SARS-CoV-2 negativization compared to a similar group of non-iNO patients (HR 2.57, 95%CI 1.04-6.33). During the 228 treatments, iNO200 and iNO200/20 groups were comparable for safety, hemodynamic stability, and respiratory function improvement. CONCLUSIONS:iNO200/20 and iNO200 are equally safe in non-intubated patients with COVID-19-induced respiratory failure with regards to MetHb and NO2. Larger studies should investigate whether iNO200/20 leads to better outcomes compared to non-iNO treated patients.

Актуальность. В кардиохирургии многократно продемонстрирован органопротективный эффект периоперационной доставки оксида азота в отношении сердца и почек, однако знания о ее способности профилактировать респираторные осложнения крайне ограниченны. Цель. Изучить эффективность периоперационной доставки оксида азота в профилактике респираторных осложнений при кардиохирургических операциях в условиях искусственного кровообращения у пациентов с повышенным риском неблагоприятных респираторных событий, доказать ее безопасность и выявить факторы риска послеоперационной острой дыхательной недостаточности. Методы. В проспективное рандомизированное контролируемое исследование включили 132 кардиохирургических пациента с повышенным риском неблагоприятных респираторных событий и разделили на две группы. Субъектам основной группы доставляли оксид азота в концентрации 80 ppm в течение всей операции и первых 6 ч послеоперационного периода. Первичной конечной точкой была величина отношения парциального давления кислорода в артериальной крови к фракции вдыхаемого кислорода через 24 ч после операции. Результаты. Доставка оксида азота приводила к увеличению отношения парциального давления кислорода в артериальной крови к фракции вдыхаемого кислорода (p < 0,001) через 24 ч после операции, была ассоциирована со снижением фракции легочного шунта (p < 0,001), частоты острой дыхательной недостаточности (p = 0,042) и послеоперационной пневмонии (p = 0,013). Доставка оксида азота не сопровождалась повышением уровня метгемоглобина ≥ 5 % и концентрации диоксида азота ≥ 3 ppm. Частота острой дыхательной недостаточности через 24 ч после операции была связана с гемотрансфузией (p = 0,033), продолжительностью искусственного кровообращения более 97 мин и продолжительностью искусственной вентиляции легких более 628 мин. Заключение. Периоперационная доставка оксида азота 80 ppm при кардиохирургических операциях в условиях искусственного кровообращения безопасна, улучшает оксигенирующую функцию легких и ассоциирована с уменьшением частоты легочных осложнений. Гемотрансфузия, продолжительность искусственного кровообращения и продолжительность искусственной вентиляции легких являются факторами риска острой дыхательной недостаточности через 24 ч после кардиохирургических операций у пациентов с повышенным риском неблагоприятных респираторных событий. Поступила в редакцию 23 сентября 2024 г. Исправлена 2 октября 2024 г. Принята к печати 7 октября 2024 г. Финансирование Исследование выполнено в рамках государственного задания по теме фундаментальных научных исследований № 122123000017-3. Конфликт интересов Авторы заявляют об отсутствии конфликта интересов. Вклад авторов Концепция и дизайн работы: Н.О. Каменщиков, И.В. Кравченко, Ю.К. Подоксенов, Б.Н. Козлов Сбор и анализ данных: И.В. Кравченко, М.А. Тё, Е.А. Чурилина, М.С. Козулин, А.М. Гусакова, Т.П. Калашникова Статистическая обработка данных: И.В. Кравченко, Ю.К. Подоксенов Написание статьи: И.В. Кравченко, Ю.К. Подоксенов Исправление статьи: Н.О. Каменщиков, Б.Н. Козлов Утверждение окончательного варианта статьи: Н.О. Каменщиков, Ю.К. Подоксенов, И.В. Кравченко, Б.Н. Козлов, М.А. Тё, Т.П. Калашникова, Е.А. Чурилина, М.С. Козулин, А.М. Гусакова

Актуальность. Оперативные вмешательства в условиях искусственного кровообращения и циркуляторного ареста осложняются нарушением микроциркуляции в тканях, при этом ведущим патогенетическим фактором ишемически-реперфузионного повреждения является митохондриальная дисфункция при гипоксии. В этой связи поиск методов органопротекции крайне актуален, а применение оксида азота ввиду его плюрипотентных свойств выглядит много­обещающим. Цель. Изучить митохондриальное повреждение в биоптатах почек под воздействием искусственного кровообращения и циркуляторного ареста при моделировании кардиохирургической операции и оценить органопротекцию оксидом азота в эксперименте. Методы. Исследование выполнено на баранах алтайской породы и включало моделирование искусственного кровообращения и циркуляторного ареста. В первой группе (n = 6) проводили интраоперационную донацию оксида азота. Во второй группе (n = 6) не осуществляли донацию оксида азота. Оценивали митохондриальное повреждение в биоптатах почек посредством измерения трансмембранного потенциала и Са2+-связывающей способности митохондрий, а также концентрации аденозинтрифосфата и лактата. Результаты. Терапия оксидом азота сопровождалась меньшей степенью митохондриальной дисфункции в биоптатах почек по сравнению с контрольной группой. Заключение. Энергетическое обеспечение тканей в условиях искусственного кровообращения и циркуляторного ареста в эксперименте улучшается на фоне донации оксида азота в концентрации 80 ppm. Поступила в редакцию 11 февраля 2024 г. Исправлена 28 марта 2024 г. Принята к печати 29 марта 2024 г. Финансирование Исследование выполнено в рамках государственного задания «Защита органов оксидом азота в сердечно-сосудистой хирургии: технологическая поддержка (устройства синтеза и доставки), механизмы реализации защитных эффектов и влияние на клинические исходы» (тема № 122123000017-3). Конфликт интересов Авторы заявляют об отсутствии конфликта интересов. Вклад авторов Концепция и дизайн работы: А.М. Бойко, Н.О. Каменщиков, Ю.К. Подоксенов, Л.Н. Маслов, Б.Н. Козлов Сбор и анализ данных: А.М. Бойко, Ю.С. Свирко, В.А. Луговский, А.В. Мухомедзянов, Б.А. Базарбекова Статистическая обработка данных: И.В. Кравченко Написание статьи: А.М. Бойко Исправление статьи: Н.О. Каменщиков, А.Г. Мирошниченко, Ю.К. Подоксенов, М.Л. Дьякова, К.А. Петлин, Д.С. Панфилов, Б.Н. Козлов Утверждение окончательного варианта статьи: все авторы

Introduction: One of the promising areas of nephroprotection in cardiac surgery is perioperative nitric oxide donation. The combined using of Goal-Directed Perfusion (GDP), Kidney Disease Improving Global Outcomes (KDIGO) and nitric oxide delivery strategies can reduce the incidence of acute kidney injury by targeting different links in the pathogenesis of kidney injury. Objective: To assess the nephroprotective properties of nitric oxide delivery in combination with KDIGO and GDP strategies during cardiac surgery with cardiopulmonary bypass in patients with chronic kidney disease.Methods: The study included 136 cardiac surgery patients with chronic kidney disease. The patients were randomized into 2 groups of 68 individuals each. The complex of non-pharmacological nephroprotection methods KDIGO and GDP was used in the control group. In the main group, perioperative delivery of nitric oxide was performed along with a set of KDIGO and GDP measures.Results: In the main group, the incidence of acute kidney injury was significantly lower compared to the control: 23.5% versus 39.7% (p = 0.043), respectively. Both groups did not differ in the concentration of renal injury biomarkers. In the control group, the concentration of exhaled nitric oxide significantly decreased 2 hours after surgery (p < 0.001), while in the main group no changes were recorded (p = 0.966). Conclusion: During cardiac surgery in patients with chronic kidney disease, delivery of nitric oxide in combination with the KDIGO and GDP measures reduced the incidence of acute kidney injury compared with the isolated using of non-pharmacological nephroprotective methods via leveling the perioperative deficiency of endogenous nitric oxide but did not affect the expression of kidney injury biomarkers. ClinicalTrials.gov ID NCT05757557 Received 31 October 2024. Revised 21 November 2024. Accepted 22 November 2024. FundingThe study was performed within the framework of the state assignment (topic No. 122123000017-3). Conflict of interestThe authors declare no conflict of interest. Contribution of the authorsConception and study design: M.A. Tyo, N.O. Kamenshchikov, Yu.K. Podoksenov, B.N. KozlovData collection and analysis: M.A. Tyo, I.V. Kravchenko, E.A. Churilina, Yu.S. SvirkoStatistical analysis: M.A. Tyo, I.V. KravchenkoDrafting the article: M.A. TyoCritical revision of the article: N.O. Kamenshchikov, Yu.K. Podoksenov, B.N. KozlovFinal approval of the version to be published: M.A. Tyo, Yu.K. Podoksenov, I.V. Kravchenko, E.A. Churilina, Yu.S. Svirko, B.N. Kozlov, N.O. Kamenshchikov

Performing cardiac surgery under cardiopulmonary bypass (CPB) and circulatory arrest (CA) provokes the development of complications caused by tissue metabolism, microcirculatory disorders, and endogenous nitric oxide (NO) deficiency. This study aimed to investigate the potential mechanisms for systemic organoprotective effects of exogenous NO during CPB and CA based on the assessment of dynamic changes in glycocalyx degradation markers, deformation properties of erythrocytes, and tissue metabolism in the experiment. A single-center prospective randomized controlled study was conducted on sheep, n = 24, comprising four groups of six in each. In two groups, NO was delivered at a dose of 80 ppm during CPB (“CPB + NO” group) or CPB and CA (“CPB + CA + NO”). In the “CPB” and “CPB + CA” groups, NO supply was not carried out. NO therapy prevented the deterioration of erythrocyte deformability. It was associated with improved tissue metabolism, lower lactate levels, and higher ATP levels in myocardial and lung tissues. The degree of glycocalyx degradation and endothelial dysfunction, assessed by the concentration of heparan sulfate proteoglycan and asymmetric dimethylarginine, did not change when exogenous NO was supplied. Intraoperative delivery of NO provides systemic organoprotection, which results in reducing the damaging effects of CPB on erythrocyte deformability and maintaining normal functioning of tissue metabolism.

Cardiac surgery is associated with high risks of complications, and these risks increase when it comes to aortic surgery because of the technical complexity of the surgeries, the use of cardiopulmonary bypass (CPB) and “circulatory arrest” (CA) that leads to ischemia-reperfusion damage. Abdominal complications in cardiovascular surgery are not the most common complications but are associated with high mortality. Protecting the gastrointestinal (GI) organs from ischemia-reperfusion injury is still a serious problem. According to a study of the organoprotective properties of nitric oxide (NO), its effectiveness in the treatment of diseases of the cardiovascular system, lungs, and kidneys has been proven, and observational results have shown that patients who were administered NO were less prone to complications from the gastrointestinal tract. The aim of the study was to evaluate the protective properties of NO for the intestines during simulated surgery under CPB and hypothermic CA. Methods. The study was conducted on sheep (n = 24). The animals were divided into 4 groups: the “CPB” group with the standard CPB protocol, the “CPB + NO” group with CPB and NO administration, the “CPB + CA” group with the standard CPB and CA protocol, and the group “CPB + CA + NO” with CPB and CA and NO administration. Instrumental and laboratory parameters were monitored at all stages of the experiment to assess the effectiveness and safety of CPB and CA simulation. In intestinal biopsy samples, the changes in the defecation rate, the concentration of a biochemical marker of intestinal ischemia (intestinal enterocyte fatty acid binding protein – i-FABP), and tissue concentrations of adenosine triphosphate (ATP) and lactate were assessed. Results . A higher rate of defecation was established (p = 0.046) in the “CPB + NO” group after CPB compared to the “CPB” group. The concentration of i-FABP in the CPB + NO group after CPB was lower compared to that in the CPB group (p = 0.002), and it was lower in the “CPB + CA + NO” group compared to the “CPB + CA” group (p = 0.033). 1 hour after CPB, the tissue concentration of ATP in intestinal biopsies in the “CPB + NO” group was higher than in the CPB group (p = 0.005). Conclusion . When modeling CPB and CA in the experiment, a positive effect of NO therapy on the intestine was noted: the functional state improved, the concentration of i-FABP decreased, and the concentration of ATP in intestinal biopsies increased.

The aim of the study was to evaluate the antimicrobial effect of single and repeated nitric oxide (NO) exposure on the major pathogens of nosocomial pneumonia isolated from the sputum of cardiac surgery patients.Materials and Methods. A 24-hour culture of microorganisms from pan-resistant isolates of Pseudomonas aeruginosa, Escherichia coli, Acinetobacter baumannii, and Klebsiella pneumoniae from the sputum of inpatient cardiac surgery patients with nosocomial pneumonia, as well as strains of P. aeruginosa and E. coli from the American Type Culture Collection (ATCC), were exposed to 200 ppm NO (experimental sample) or medical air (control sample) in a sealed chamber for 30 minutes. After a single or 4 repeated gas exposure at 4 h intervals, Petri dishes were placed in a thermostat at 37°C and the results were evaluated at 24 and 48 h or at 12, 24, 36 and 48 h, respectively. Grown colonies were counted using an automated colony counter and recorded as CFU/mL.Results. No growth of clinical isolates of P. aeruginosa and E. coli was observed 24 and 48 h after a single exposure to NO. Growth of A. baumannii was lower compared to controls at 24 h but continued at 48 h. No effect of a single exposure to 200 ppm NO on other microorganisms was observed. After 4 exposures to NO, the growth of ATCC E. coli was not detected, the growth of other experimental strains was significantly lower compared to the control (P<0.05).Conclusion. Our results provide a rationale for the use of multiple intermittent inhalation of 220 ppm NO for the treatment of patients with hospital-acquired bacterial pneumonia.

Enhancement of methods for protecting target organs during coronary artery bypass surgery determined the development of a technology for delivering nitric oxide (NO) to the systemic blood flow using a cardiopulmonary bypass (CB) apparatus, which makes NO available to all organs and tissues.The aim of the study was to access the effect of perioperative NO conditioning on the coefficients of microviscosity and polarity of sheep etythrocyte membranes during experimental surgical intervention using CB.Material and methods. Study was carried out on 20 sheep weighing 30–34 kg. Two groups were formed. In the CB group, 10 sheep underwent the standard clinical protocol of artificial lung ventilation (ALV) and CB. In the CB + NO group, 10 sheep received NO at a dose of 80 ppm through the circuit of ALV apparatus immediately after tracheal intubation. At the start of CB, NO was delivered to the extracorporeal circulation circuit at a dose of 80 ppm for 90 min. After disconnection from CB, NO supply continued through the ALV apparatus at a dose of 80 ppm for 60 min. The coefficients of microviscosity and polarity of sheep erythrocyte membranes were determined by spectrofluorimetry using pyrene probe.Results and discussion. The implementation of CB was accompanied by a statistically significant decrease in the microviscosity coefficient in the zones of proteinlipid contact of sheep erythrocyte membranes. In the zone of total lipids, the microviscosity coefficient did not change after CB implementation. The membrane polarity coefficient at the final stage of the surgery increased significantly in the zone of annular lipids and did not change in the zone of total lipids. NO supply to the circuit of the extracorporeal circulation neutralizes the revealed increase in the microviscosity and polarity of the annular lipids.Conclusions. The introduction of NO into the extracorporeal circulation circuit at the concentration of 80 ppm prevents a decrease in the coefficients of microviscosity and polarity of annular lipids of erythrocyte membranes that occurs during cardiac surgery.

Introduction: Surgical interventions under cardiopulmonary bypass and circulatory arrest are complicated by impaired microcirculation in tissues; during hypoxic period the mitochondria dysfunction becomes the leading pathogenetic factor of ischemia-reperfusion injuries. In this regard, the search for methods of organ protection seems to be an extremely urgent task. The using of nitric oxide can be a promising technique given its pluripotent properties.Objective: The study was aimed to examining of mitochondria injuries in kidney biopsies stipulated by cardiopulmonary bypass and circulatory arrest when simulating cardiac surgery, as well as to assessing the potentials of organ protection with nitric oxide in the experiment.Methods: The study was carried out on Altai breed sheep and included simulating of cardiopulmonary bypass and circulatory arrest. The first group (n = 6) was provided with intraoperative nitric oxide donation. The second group (n = 6) served as a control (without nitric oxide donation). Mitochondria injuries were assessed in kidney biopsies by measuring transmembrane potential and Ca2+-binding capacity of organelles, as well as by determining ATP and lactate concentrations.Results: Nitric oxide therapy was associated with less mitochondria dysfunction in kidney biopsies compared with the control group. There was a steady trend to the amelioration of the energy maintenance in the renal parenchyma in the nitric oxide donation group.Conclusion: A steady trend towards optimizing the energy supply of tissues under cardiopulmonary bypass and circulatory arrest was revealed in an experiment against the background of NO donation at a concentration of 80 ppm. Received 11 February 2024. Revised 28 March 2024. Accepted 29 March 2024. Funding: The The study was carried out within the framework of the state assignment “Protection of organs by nitric oxide in cardiovascular surgery: technological support (synthesis and delivery devices), mechanisms for implementing protective effects and impact on clinical outcomes” (topic No. 122123000017-3). Conflict of interest: The authors declare no conflict of interest. Contribution of the authors Conception and study design: A.M. Boyko, N.O. Kamenshchikov, Yu.K. Podoksenov, L.N. Maslov, B.N. Kozlov Data collection and analysis: A.M. Boyko, Yu.S. Svirko, V.A. Lugovskiy, A.V. Mukhomedzyanov, B.A. BazarbekovaStatistical analysis: I.V. KravchenkoDrafting the article: A.M. Boyko Critical revision of the article: N.O. Kamenshchikov, A.G. Miroshnichenko, Yu.K. Podoksenov, M.L. Diakova, K.A. Petlin, D.S. Panfilov, B.N. KozlovFinal approval of the version to be published: A.M. Boyko, N.O. Kamenshchikov, A.G. Miroshnichenko, Yu.K. Podoksenov, Yu.S. Svirko, V.A. Lugovskiy, M.L. Diakova, I.V. Kravchenko, A.V. Mukhomedzyanov, L.N. Maslov, B.A. Bazarbekova, K.A. Petlin, D.S. Panfilov, B.N. Kozlov

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. Acute kidney injury is a common complication of cardiac surgery with cardiopulmonary bypass. Ischemic-reperfusion injury, systemic inflammation, oxidative stress, and other factors that occur during cardiopulmonary bypass lead to disruption of energy supply and death of kidney tissue cells. Delivery of nitric oxide is a promising method of nephroprotection during cardiosurgical operations with cardiopulmonary bypass.Aim: To study the parameters of energy supply of the renal tissue during cardiopulmonary bypass with nitric oxide delivery in the experiment.Material and Methods. A prospective controlled experimental study was performed on 12 rams. Animals were included in 2 equal groups at a ratio of 1:1. In the main group, nitric oxide was delivered at a dose of 80 ppm immediately after tracheal intubation and within 90 minutes of cardiopulmonary bypass (main group, n = 6). In the control group, mechanical ventilation and cardiopulmonary bypass were performed according to standard protocols (control group, n = 6). Biopsy specimens of kidney tissue were taken 1 hour after weaning from cardiopulmonary bypass. Energy supply was assessed (according to the tissue concentration of adenosine triphosphate (ATP) and lactate).Results. Delivery of nitric oxide was not accompanied by tissue perfusion aberration during cardiopulmonary bypass (CPB). The level of free hemoglobin in both groups was statistically significantly higher 1 hour after cardiopulmonary bypass compared with the stages of intubation – p < 0.000... and the beginning of CPB – p < 0.000... The ATP value significantly differed between groups and amounted in the control group 3.7 ± 0.62 nmol/g; in the main group 6.8 ± 1.11 nmol/g, р = 0.00011. The lactate concentration did not differ statistically significantly between the groups and amounted to: in the control group 12.9 ± 3.71 nmol/g; in the main group 10.2 ± 2.14 nmol/g, р = 0.1502.Conclusion: Delivery of nitric oxide improved the parameters of energy supply of the renal tissue during cardiopulmonary bypass in the experiment.

HighlightsFor the first time, the incidence and timing of the development of postoperative pneumonia in patients undergoing surgical reconstruction of the aortic arch in the post-covid period were studied. Risk factors for pneumonia and predictors of the severe course of the disease in this cohort of patients were identified. The results obtained will make it possible to differentiate patients at risk of developing pneumonia from the general population of patients undergoing surgical reconstruction of the aortic arch for targeted perioperative prevention of this complication. AbstractAim. To study the incidence of nosocomial pneumonia (NP) after aortic arch surgery, and to determine the impact of perioperative factors on the risk for its development and severity of its course.Methods. A retrospective analysis of 66 case histories of patients who underwent aortic arch surgery in 2022 was carried out. The incidence and timing of the development of pneumonia were revealed, the severity of its course was assessed. The impact of the main demographic, clinical, perioperative factors on the risk for the pneumonia development and the severity of its course was studied.Results. The incidence of pneumonia after aortic arch surgery was 24.2%. A relationship between smoking (OR 1.17; 95% CI [0.23; 1.43], p = 0.007), smoking index (OR 0.99; 95% CI [0.92; 1.07], p = 0.002) and the risk of NP developing as well as between the duration of mechanical ventilation and the severity of NP was found with a univariate logistic regression analysis (OR 1.26; 95% CI [1.0; 1.59], p = 0.049).Conclusion. The risk for NP development in patients who underwent thoracic aortic surgery is associated with smoking and smoking intensity in the preoperative period. The predictor of the severe course of NP is the duration of mechanical ventilation.

Aim. To evaluate the efficiency and safety of nitric oxide delivery for kidney protection in the simulation of cardiopulmonary bypass and circulatory arrest in the experiment.Materials and Methods. We performed an experimental modeling of cardiopulmonary bypass with circulatory arrest in 20 sheep of the Altai breed weighing 30-32 kg. Circulatory arrest was performed at moderate hypothermia (30-32°C) for 15 minutes and was followed by reperfusion and warming up to 37°C. Animals were divided into 2 equal groups: 10 sheep which received nitric oxide (NO) through the inhalations supply and cardiopulmonary bypass machine at a dose of 80 ppm, and 10 control sheep. We further collected biological fluids and tissue specimens for subsequent assessment of the safety of NO use and its nephropro-tective properties.Results. The proposed method of NO therapy during the cardiopulmonary bypass with circulatory arrest was safe and did not lead to an increase in toxic metabolites. In sheep which received NO therapy, the average concentration of NO2 throughout the entire period of the experiment was 1.2 ± 0.19 ppm (with a maximum allowable concentration of 3.0 ppm), and the concentration of methemoglobin (MetHb) was 2.3 ± 0.34% (with a maximum allowable level of 5.0%). Neutrophilic gelatinase-associated lipocalin (NGAL) was significantly lower in sheep which received NO therapy (0.67 ± 0.255 ng/mL versus 2.23 ± 0.881 ng/mL in the control group, p = 0.0001). Acute kidney injury was mitigated in sheep which received NO therapy.Conclusion. Experimental delivery of NO at a dose of 80 ppm during the cardiopulmonary bypass and circulatory arrest is safe and is associated with reduced acute kidney injury.

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.