Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) may be a critically important method for supporting patients with acute STsegment elevation coronary syndrome (STEMI) undergoing percutaneous coronary intervention (PCI) in high-risk settings.Objective: to demonstrate the effectiveness of ECMO in a patient with severe cardiovascular insufficiency against the background of myocardialischemia in conditions of ongoing intensive careClinical observations: a case of the use of VA-ECMO before PCI in a 63-year-old patient with multiple occlusive stenotic lesions of the coronary bed is described. Due to the high risk of complications during planned PCI and ongoing CPR, it was decided to start VA-ECMO to provide mechanical circulatory support. Balloon angioplasty was performed with stenting of the LCA trunk and permanent residence with 2 stents in conditions of extracorporeal life support. After stenting, an effective sinus rhythm was independently restored. On the 4th day, decannulation and excommunication from ECMO were performed. On the 7th day, the patient was transferred from the ICU to the cardiology department. The patient was discharged on the 18th day.Conclusion: the use of ECMO contributed to the stabilization of the patient’s vital signs in conditions of acute myocardial ischemia and made it possible to perform effective recanalization against the background of resuscitation measures.

RELEVANCE. In conditions of increased sensitivity of damaged brain tissue to disruption of homeostasis, it is important to achieve stabilization of the vital functions of the body as soon as possible. Given the excess afferent impulse, adequate sedation and analgesia are an integral component of intensive care for patients with traumatic brain injury. The use of halogenated anesthetics is associated with a lower risk of complications associated with long-term sedation with intravenous drugs. In the example of two patients with severe traumatic brain injury, the effectiveness and safety of sevoflurane for prolonged inhalation sedation was noted. This study was approved at a meeting of the Local Ethics Committee of the Federal Scientific and Clinical Center for Resuscitation and Rehabilitation, an extract from protocol No. 5/21/1 dated December 23, 2021, as well as at a meeting of the LEC of the N. V. Sklifosovsky Research Institute for Emergency Medicine of the Moscow Health Department, meeting No. 1-2022 dated January 11, 2022. AIM OF STUDY. To demonstrate the safety of inhalation sedation in patients with traumatic brain injury using clinical observations as an example. MATERIAL AND METHODS. An analysis of two clinical observations of patients with severe traumatic brain injury was carried out. The effectiveness and safety of prolonged inhalation sedation was assessed by indicators: intracranial pressure, dynamics of mean arterial pressure and blood saturation in the jugular vein bulb, as well as the total duration of artificial ventilation and stay in the intensive care unit. Clinical observation No. 1. Patient B., 41 years old, was admitted with cerebral insufficiency (GCS 8) with damage to the soft tissues of the head. As a result of the examination, the patient wasdiagnosed with “Closed craniocerebral injury.” Fracture of the bones of the vault and base of the skull. Severe brain contusion. Traumatic subarachnoid hemorrhage, acute subdural hematoma in the left frontotemporal region 3 cm3”. Considering the size of the trauma (65 cm3) and the life-threatening dislocation syndrome, the patient underwent surgical intervention: “Decompressive craniotomy, removal of contusion areas. Installation of a ventricular intracranial pressure sensor.” The early course of the postoperative period was complicated by the development of infectious complications, which led to the need for prolonged sedation in the intensive care unit. On the 3rd day, a lower tracheostomy was performed. The total time of sedation was 3 days, and the duration of artificial ventilation was 10 days. On the 21st day, the patient was decannulated and transferred to a specialized department. Clinical observation No. 2. Patient K, 42 years old, was admitted to the hospital with a depressed level of consciousness (GCS 6). Based on the results of the examination, a diagnosis was made: “Penetrating traumatic brain injury with severe brain contusion, a focus of crush contusion in the right temporal lobe, acute subdural hematoma of the right frontal-temporo-parietal region 100 cm3 and a fracture of the bones of the vault and base of the skull, facial skeleton, micropneumocephaly”. Considering the size and location of the hematoma, the patient underwent surgery including decompressive craniotomy, removal of an acute subdural hematoma, and a Spiegelberg intracranial pressure sensor was installed. In the early postoperative period, severe hemodynamic instability associated with vascular insufficiency of central origin was noted. The use of inhalational sedation sevoflurane did not lead to the development of intracranial hypertension and escalation of vasopressor therapy. The total time of use of sevoflurane was 36 hours. Spontaneous breathing was restored by the 18th day. The patient’s stay in the ICU was 31 bed days. CONCLUSION. Based on the data obtained, we may conclude that the use of inhalation sedation in this category of patients is safe, as well as the absence of a significant effect of sevoflurane on the level of intracranial pressure and central hemodynamic parameters. However, secondary complications that developed in patients do not allow us to draw an unambiguous conclusion about the effect of this method of sedation on the duration of artificial ventilation and stay in the intensive care unit. Only the accumulation of a sufficient volume of clinical material will reveal all the advantages and disadvantages of this method.

The aim of the study. To study the effect of ley-enkephalin synthetic analogue on the dynamics of inflammatory response markers and organ dysfunction in patients with severe combined trauma.Materials and methods. A prospective clinical study with historical control from two clinical centers — N. I. Pirogov State Clinical Hospital No. 1 and N.V. Sklifosovsky Clinical and Research Institute for Emergency Medicine — included men and women with severe combined trauma and the ISS scores values of 18–44, aged 18 to 70 years. Diagnostic and therapeutic approaches in all patients followed current international, national& local protocols and 2022 clinical recommendations of the Russian Society of Surgeons «Combined and multiple trauma in combination with shock (Polytrauma)». In the study group, treatment was supplemented with extended (72 hours from the admission) infusion of the test drug through a syringe dispenser following the study protocol. Effects of the test drug prolonged infusion were evaluated for the following laboratory parameters: levels of cortisol, procalcitonin, interleukin 6, NTproBNP and leukocyte count. Laboratory tests were performed at 4 time points: prior to test drug infusion, 24 hours and 72 hours after initiation of infusion, and on Day 7. The study evaluated patient’s dynamics using APACHE II, SOFA and SAPS II scales and percentage of patients developing organ dysfunction (renal, respiratory, cardiovascular), rates of sepsis complications and mortality.Results. Patients who received the test drug had significantly lower concentrations of systemic inflammatory response markers, i. e. PCT (P=0.001) and IL-6 (P=0.010) after 24 hours of follow-up vs the control group patients. The incidence of ARDS has also decreased in the study group (P=0.011 vs control). Acute kidney injury (AKI) rate was insignificantly higher in the control group (P=0.349). The duration of hospital stay in the control group was 35 (17; 51) days vs 18 (14; 30) days in the study group (P=0.140)Conclusion. The use of ley-enkephalin synthetic analogue inhibits production of such key systemic inflammatory response markers as PCT and IL-6, and reduces PCT concentrations within 24 hours in patients with severe combined trauma. ARDS developed less frequently in the study group, but there was no significant difference in the incidence of AKI, AHF and infectious complications between the groups.

The aim of the study was to evaluate the usefulness and safety of sevoflurane in patients in the acute phase of severe traumatic brain injury (TBI).Materials and methods. A prospective, randomized, pilot clinical trial was conducted at the Sklifosovsky Research Institute for Emergency Medicine (Moscow) in adults with acute severe TBI, aged 18 years and older, undergoing intensive intracranial pressure (ICP)-guided therapy. To achieve the desired sedative effect, the inhaled anesthetic sevoflurane was administered in the main group, and standard doses of intravenous propofol were administered in the control group. ICP and cerebral oxygen extraction fraction (OEF) were monitored in all patients. Hemodynamic and respiratory support parameters, transcranial Doppler ultrasound scan, brain bioelectrical activity, brain CT scan, laboratory parameters, markers of inflammation, patients' need for sedation and mechanical ventilation, and length of ICU stay were also evaluated.Results. The use of inhalation sedation contributed to the reduction of ICP on day 2 (9.5 mmHg in the sevoflurane group and 17.3 mmHg in the propofol group, P=0.003) and day 3 (10 mmHg and 14.2 mmHg, respectively, P=0.005). BIS monitoring showed no significant difference in depth of sedation between groups on day 2 (60 vs. 48.5, P=0.070) and day 3 (61 vs. 46, P=0.095). Inhalation sedation reduced cerebral OEF on the injury side compared to propofol on day 2 (23.3 vs. 30.2%, P=0.006) and day 3 (22.7 vs. 31.2%, P<0.001). After 24 hours of sedation therapy, there was a significant difference in P/F (PaO₂/FiO₂) ratios between the groups. On days 1, 3, and 7, the sevoflurane group had P/F ratios of 340, 324, and 323 mmHg, while the propofol group had significantly lower ratios of 271, 278, and 275 mmHg (P<0.001). Pneumonia was documented in 9 cases in the sevoflurane group vs. 18 cases in the propofol group (P=0.028), and a similar trend was observed in the total number of infectious complications: 13 vs. 21 cases, respectively (P=0.046).Conclusion. Sevoflurane in the acute phase of severe TBI was not only safe, but also improved several vital functions, including ICP, blood pressure, P/F ratio, and also slowed brain metabolism via reduced oxygen consumption without affecting the depth of sedation according to BIS monitoring data. All of the above suggests that inhalation sedation may improve the prognosis for patient recovery. However, multicenter randomized clinical trials are needed to identify and verify all positive and negative effects of inhalation sedation in this patient population.

We studied the effect of 2-h inhalation of argon-oxygen mixture (Ar 70%/O2 30%) after photochemically induced stroke and on days 2 and 3 after stroke modeling on the severity of neurological deficit and brain damage (by MRI data) in Wistar rats. Neurological deficit was assessed within 14 days using the limb placement test. MRI and histological study of the brain with an assessment of the size of damage were performed on day 14 after ischemia. Significant differences were obtained in limb placement scores on days 3, 7, and 14, as well as in the volume of ischemic focus by MRI in comparison with the control (ischemia+N2 70%/O2 30%). Inhalation of argon-oxygen mixture for 2 h a day over 3 days after photoinduced stroke decreased the volume of brain damage by 2 times and reduced the severity of neurological deficit.

Introduction. Pain in the intensive care unit is a common problem in patients with acute pancreatitis of various etiologies. Given the severity of the pain syndrome, as well as the low effectiveness of nonsteroidal anti-inflammatory drugs or antispasmodic therapy, it is often necessary to resort to the administration of opioid analgesics or epidural analgesia. Each of these pain management methods has certain disadvantages and contraindications, which makes it urgent to search for a safe and effective method of relieving pain in patients with pancreatitis or pancreonecrosis.Goal. To determine the effectiveness blockade of the nerves of the fascial space of the muscles’ erector spine in acute pancreatitis. Clinical observation. Patient X., 58 years old, was arrived to the emergency department of the V.M. Buyanov State Clinical Hospital with severe pain in the epigastric region (10 points out of 10 on the visual-analog scale).Conclusions. ESPB in a patient with acute biliary pancreatitis complicated by pancreonecrosis allowed to control pain syndrome quickly and safely. Further randomized clinical trials will allow to implement and optimize the technique, improving the clinical outcome.

In addition to high mortality, craniocerebral injuries have another danger, a long rehabilitation period and a high percentage of disability with the development of cognitive impairment. This is primarily associated with the processes of neuroinflammation, which development, according to recent data, leads to a long-term impairment of consciousness. The anti-inflammatory effects of xenon inhalation anesthetic, which have been repeatedly shown in previous studies, have the potential to beneficially affect the level of consciousness in these patients by targeting key links of neuroinflammation.AIM OF STUDY To evaluate the effect of oxygen-xenon mixture inhalation on the level of consciousness recovery and the severity of spastic activity in patients after traumatic brain injury.MATERIAL AND METHODS A prospective randomized clinical trial of the effect of inhaled xenon sedation on the level of consciousness and spastic activity in patients with post-coma long-term impairment of consciousness was conducted. Patients were randomized into two equal groups. In group I (comparisons, n=15) (in addition to the standard treatment after a traumatic brain injury), each patient included in the study underwent 7 sessions of inhalation of an air-oxygen mixture with an oxygen content of at least 30 vol% for 30 minutes. In group II (study, n=15) (in addition to standard treatment), each patient included in the study inhaled an oxygen-xenon gas mixture (xenon content 30 vol%) for 7 days 1 time per day. Before and after the course of treatment (on the 7th day), patients were assessed using the CRS-R scale and the modified Ashworth scale.RESULTS The final evaluation included 12 patients from the comparison group and 12 patients from the study group. Three patients were excluded from each group as a result of critical incidents not related to the type of the therapy. In the comparison group on the 7th day, the level of consciousness was score 9 [7; 11] and did not differ statistically significantly from the baseline (p>0.05), which was score 8 [6; 10]. Spastic activity also did not change statistically significantly. In group II, the initial level of consciousness was 9 [7; 10], and on the 7th day — score 15 [12; 17], which was statistically significantly higher both in relation to the level of consciousness by the 1st day (p=0.021) within the group, and in relation to it on the 7th day in group I (p=0.038). When comparing spastic activity on the 1st and 7th days, we did not obtain a statistically significant difference in any of the groups.CONCLUSION Our method of xenon inhalation made it possible to have a beneficial effect on the level of consciousness of patients after traumatic brain injury, but this did not affect the final level of spastic activity in any way.

ABSTRACTS Ischemic stroke occupies a leading position among the causes of mortality and disability. Long-lasting motor and cognitive impairments, a decrease in the level of consciousness over time aggravate the course of the disease, leading to immobilization syndrome and comorbidity load, which contributes to the development of life-threatening conditions in this category of patients. In this regard, the search for new neuroprotective strategies used at an early stage and capable of minimizing the severe consequences of stroke for the patient in particular and society as a whole seems extremely relevant. The paper presents the effect of inhaled xenon for sedation in patients with severe ischemic stroke on the level of consciousness and severity of neurological disorders, and also shows its effect on S100B protein, a marker for blood brain barrier damage. AIM OF STUDY To evaluate the effect of inhaled xenon for sedation in comparison with propofol intravenous sedation on the dynamics of the level of consciousness, the severity of neurological dysfunction and changes in the concentration of astroglial-derived S100B protein in severe ischemic stroke. MATERIAL AND METHODS The research was conducted on two groups of patients comparable in age, gender, comorbid background, as well as the severity of the underlying disease. In both groups, the condition of patients required the start of mechanical ventilation immediately after admission to the intensive care unit. Group I (control, n=12). After intubation and the start of ventilation, patients were sedated with propofol at a dose of 1-2 mg/ kg / hour for 24–72 hours. Group II (xenon, n=12). After intubation and the start of ventilation, patients underwent xenon inhalation at a concentration of 40 vol. % for the first 6 hours. If it was necessary to continue sedation after the end of xenon inhalation, propofol was used in doses similar to Group I. Neurological status was assessed on days 1, 3 and 8 using the Glasgow Coma Scale (GCS), the Full Outline of UnResponsivness (FOUR) score and the National Institutes of Health Stroke Scale (NIHSS). The critical analysis of the value of S100B as a marker of brain damage was carried out before the start of sedation, on the 3rd and 8th days. RESULTS Xenon inhalation (40 vol. %) in comparison with propofol intravenous sedation significantly increases the level of consciousness in patients with severe ischemic stroke (p=0,026), reduces neurological disorders assessed using NIHSS (p=0,007) on day 7, and also reduces serum S100B levels on day 3 (p<0,05) after ischemic stroke. CONCLUSION Our open randomized clinical trial of xenon inhalation versus propofol intravenous sedation revealed the neuroprotective properties of xenon anesthesia in patients with severe ischemic stroke. Based on the obtained clinical and laboratory data, it can be concluded about the effective implementation of the neuroprotective effects of xenon in the administration scheme used in the research.

Aquaporins 4 and 5 are proteins that form water channels in the cell membrane, participate in the transfer and migration of immune cells, being expressed on many cell types including CNS astrocytes, kidney cells, lungs, and the immune system. We have previously shown that AQP 5 genetic polymorphism is associated with different outcomes of abdominal sepsis. Since another common aquaporin protein, AQP 4, is also expressed on the surface of immunocompetent cells, determining cell motility, it was suggested that AQP 4 may also be important in the pathogenesis of sepsis, and that AQP 4 polymorphism may predetermine sepsis severity and outcome. AQP 4 rs1058427 genetic polymorphism has not been studied earlier. The aim of the study was to determine the effects of region 3` polymorphism in the AQP 4 gene on the clinical course and outcome of sepsis. Materials and methods. The prospective study included 290 ICU patients from three clinical hospitals in Moscow aged 18–75 years with clinical signs of sepsis (SEPSIS-3, 2016). Results. It was found that the minor T allele of the AQP 4 rs1058427 gene provides strong protection against septic shock, as among GG genotype carriers septic shock developed in 66%, but in presence of the minor T allele dropped to half of cases ( P =0.009, Fisher’s exact test, OR=1.99, 95% CI: 1.12–3.55, N =290). There was a significant association between AQP 4 rs1058427 genetic polymorphism and 30-day hospital mortality in a subgroup of patients with more severe organ dysfunction and higher comorbidity burden (cardiovascular diseases, type II diabetes mellitus) requiring extracorporeal treatment modalities and ventilator support for 5 or more days ( N =66). Carriers of the minor T allele showed better survival rates as compared AQP 4 rs1058427 GG genotype carriers (5 deaths out of 10 and 47 deaths out of 56, respectively, P =0.003, Fisher’s exact test, N =66, OR=5.22, 95% CI: 1.25–21.82, P =0.009, log-rank criterion). Conclusion. The minor AQP 4 rs1058427 T allele is associated with protection against septic shock and better survival in sepsis in a group of ICU patients with high comorbidity burden requiring extracorporeal life support interventions.

The leading role of neuroinflammation as the culprit of a long-term impairment of consciousness in patients after injuries to the central nervous system forces us to look for new effective strategies for resolving this pathological process. Xenon reducing the intensity of the inflammatory response due to the impact on several links is potentially able to have a beneficial effect on this category of patients. Using laboratory equipment, we evaluated the effect of half-hour daily inhalations of a 30% air mixture with 30% xenon for 7 days on the level of markers of neuronal damage and regeneration of nervous tissue. AIM To study the effect of inhalation of an air-xenon mixture on the dynamics of markers of neuroinflammation and restoration of nervous tissue in patients after traumatic brain injury (TBI). MATERIAL AND METHODS We conducted a prospective randomized clinical trial evaluating the effect of inhaled xenon for sedation on the level of consciousness and spasticity in patients with prolonged post-coma impairment of consciousness. Patients were randomized into 2 equal groups. In Group I (Comparison, n=15) in addition to the standard treatment for TBI, each patient included in the study underwent 7 sessions of inhalation of an air mixture with an oxygen content of at least 30 vol.% for 30 minutes. In Group II (Xenon, n=15) in addition to the standard treatment, each patient included in the study underwent a half-hour inhalation with an air-xenon gas mixture (with a xenon content of 30 vol.% and oxygen — 30 vol.%) for 7 days, 1 time per day. The levels of interleukin-6, α-1 acid glycoprotein (AGP), S100 b protein and brain-derived neurotrophic factor were assessed before the first treatment and then once a day for 6 days. RESULTS The final evaluation included 12 patients from the Comparison Group and 12 patients from the Xenon Group. The greatest difference in the concentration of interleukin-6 between the Comparison and Xenon Groups was noted on the 5th day - 12.31 (10.21; 15.43) pg/ml vs. 7.93 (3.61; 9.27) pg/ml, respectively; however, the findings only tended to be statistically significant (p=0.07). When assessing the AGP level, the maximum difference was noted on the 4th day. In the Comparison Group, the AGP level was 0.81 (0.74; 0.92) pg/ml versus 0.614 (0.4; 0.79) pg/ml in the Xenon Group. And again, the data showed only a trend towards statistical significance (p=0.09). The highest level of brain-derived neurotrophic factor in the Xenon Group was observed on the 3th day — 0.1271 (0.046; 0.2695) pg/ml, which was statistically significantly higher than the one in the Comparison Group — 0.062 (0.036; 0.121) pg/ml (p=0.04). The concentration of S100 b protein during the entire observation period in both groups did not exceed 0.005 pg/ml. CONCLUSION Xenon inhalation according to the method proposed by the authors had a beneficial effect on the processes of neural tissue regeneration, however, with regard to neuroinflammation, its effects were not so pronounced.

High concentration of sepsis-associated aromatic microbial metabolites (AMM) stands as a prognostically unfavorable factor, indicating the progression of multiple organ dysfunction and an increased risk of death in patients with sepsis and septic shock. This study is based on a hypothesis that excess of sepsis-associated AMM in patients with sepsis is caused by metabolic alterations (dysfunction) in the intestinal microbiota.The aim of this study was to compare the potential of normobiota and pathobiota to bio-transform sepsis-associated metabolites of aromatic amino acids tyrosine and phenylalanine, such as phenyllactic acid(PhLA) and 4-hydroxyphenyllactic acid (4-HPhLA).Materials and methods. Samples of intestinal contents of patients with septic shock (N=10, pathobiota) and healthy volunteers (N=9, normobiota) were placed in test tubes with the omnipurpose thioglycol medium. The clinical model of excessive inflow of sepsis-associated AMM into the intestine (for example, from blood or sites of inflammation) was reproduced in the in vitro experiment by adding PhLA or 4-HPhLA in clinically significant concentrations (25 mkM) into each test tube with pathobiota and normobiota. After incubation in a thermostat (37°, 24 hours), AMМ concentrations were measured in the samples with pathobiota and normobiota using GC-MS analysis.Results. Concentration of AMM decreased within 24 hours in the tubes with normobiota after PhLA or 4-HPhLA were added. In the tubes with pathobiota, no decrease in AMM concentrations was documented after loading with PhLA or 4-HPhLA. Concentrations of PhLA (P=0.002) and 4-HPhLA (P0.001) were statistically significantly higher in pathobiota samples compared to normobiota.Conclusion. The in vitro experiment demonstrates that after excessive load with sepsis-associated metabolites (PhLA, 4-HPhLA), the microbiota of healthy people is capable to bio-transform such metabolites to the end products of microbial metabolism, while pathobiota of septic patients exhibits altered biotransformational potential. This data demonstrate that microbiota dysfunction may contribute to the pathogenesis of sepsis.

Severe combined trauma is characterized by high mortality both among young people (above 20 %) and among the older age group (about 45 %). Correction of metabolic disorders is the most difficult task, especially in the first hours after injury.Objective. To demonstrate the effectiveness of early initiation of veno-venous hemodiafiltration on the example of successful treatment of a patient with severe combined trauma (ISS is 57 points).Clinical observation. Patient A., 19 years old, was taken to the surgical intensive care unit by an ambulance team with a directional diagnosis of ‘severe combined injury’ as a result of falling from a height of the 6th floor in a state of alcoholic intoxication. Considering the impossibility of correcting waterelectrolyte and metabolic disorders by conservative methods, it was decided to start extracorporeal treatment early in the volume of prolonged venovenous hemodiafiltration with citrate-calcium anticoagulation (Ci-Ca CVVHD). In addition, the patient received therapy within the framework of the current recommendations for the treatment of severe combined trauma. Against the background of the ongoing treatment, there was a distinct positive trend. Vasopressor support was discontinued on day 3, and on day 15 the patient was transferred to independent breathing. In total, one CVVHD session was conducted, with a total duration of 62 hours. The patient’s stay in the intensive care unit was 29 days, in the profile distance – 4 days with subsequent discharge.Conclusions. The use of the CVVHD method in a patient with severe combined trauma in the early period without the phenomena of acute kidney injury contributed to the relief of metabolic disorders with the stabilization of the homeostasis system. However, in order to form conclusions and expand indications for the use of extracorporeal detoxification methods in patients with severe combined trauma, further study of this issue is necessary.

ЦЕЛЬЮ Обзора является анализ данных литературы о перспективах и безопасности продленной седации ингаляционными анестетиками с применением устройства для ингаляционной седации испарителя AnaConDa в отделениях интенсивной терапии и реанимации. Анализ результатов исследований показал, что применение продленной ингаляционной седации в отделении реанимации пациентам, находящимся в критическом состоянии, способствует ранней активизации и реабилитации благодаря хорошей управляемости, сокращает время пребывания на искусственной вентиляции легких, оказывает нейропротекторное, кардиопротекторное, противовоспалительное, антиконвульсантное, бронходилатирующее действие, обеспечивая ряд положительных эффектов при относительно простой и безопасной технике выполнения. Можно заключить, что исследователям еще только предстоит установить преимущества или недостатки седации ингаляционными анестетиками по сравнению с седацией внутривенными препаратами в повседневной клинической практике.

One of the main problems facing intensivists when treating patients with COVID-19 is severe and critical acute respiratory distress syndrome (ARDS) with the underlying viral pneumonia. The current guidelines of the Russian Ministry of Health (Version 15 of 22.02.22) do not include drugs with a lung protective effect. This issue could be solved by administration of a synthetic analogue of leu-enkephalin.Aim. Study the efficacy of a synthetic analogue of leu-enkephalin in ARDS in patients with COVID-19.Materials and methods. The study included 35 patients divided into 2 groups. Group 1 (main) patients (n=15) in addition to standard therapy received a continuous infusion of synthetic analogue of leu-enkephalin at a rate of 5 µg/kg/hour for 5 days. Patients from group 2 (control, n=20) were treated according to the Temporary Guidelines of the Ministry of Health (V.15), but without the synthetic analogue of leu-enkephalin. The radiological data, frequency, severity and evolution of respiratory complications, changes in P/F (PaO2/FiO2) ratio, as well as changes in the scores of prognostic APACHE II, SOFA, and NEWS scales were evaluated.Results. In patients taking the studied drug, the percentage of lung damage did not change with the median (IQR) of 0 [–8; 0], while in the control group it increased by approximately 10% with the median (IQR) of +10,0 [+2; +20] (P=0.001). The proportion of patients in group 1 with positive disease evolution within 5–9 days after treatment initiation was significantly higher and reached 46.7 [24.8; 69.9]%, whereas in group 2 it was 15.0 [5.2; 36.0]% (P=0.04). Also, in group 1, starting from day 4, the median P/F ratio was significantly higher than in group 2 reaching 220 [185;245] versus 127 [111;158], respectively (P=0.014). The need for non-invasive lung ventilation in group 1 on day 7 averaged 7%, while in group 2 it was as high as 45.0%, which was significantly higher than in the main group (P=0.013).Conclusions. The use of synthetic analogue of leu-enkephalin according to the specified regimen had a significant impact on the main parameters of the viral pneumonia severity. The results serve as a rationale for the development of a novel effective treatment strategy to supplement the current standard COVID-19 management.

U podavlyayushchego chisla pacientov, perenesshih ostroe narushenie mozgovogo krovoobrashcheniya, vyyavlyayutsya ostatochnye yavleniya, iz nih u 50% — kognitivnye narusheniya, ogranichivayushchie samoobsluzhivanie v bytu, trudovuyu deyatel'nost' i social'nuyu adaptaciyu v celom i privodyashchie k invalidnosti dazhe pri otsutstvii znachitel'nyh dvigatel'nyh narushenij. Cel'yu issledovaniya bylo podobrat' naibolee effektivnuyu prodolzhitel'nost' ingalyacii ksenona s 0,5 MAK (maksimal'noj al'veolyarnoj koncentraciej) dlya snizheniya vyrazhennosti nevrologicheskih i kognitivnyh narushenij pri eksperimental'nom insul'te. Na 70 krysah smodelirovana fokal'naya ishemiya-reperfuziya po metodu Longa s posleduyushchej ingalyaciej ksenona 0,5 MAK v techenie 30, 60 ili 120 min. Nevrologicheskij deficit ocenivali s pomoshch'yu serii iz semi testov «Postanovka konechnosti na oporu», kognitivnye funkcii — testom «Vodnyj labirint Morrisa». Ekspoziciya ksenona 0,5 MAK v techenie 30 min privodila k rostu chisla ballov v teste «Postanovka konechnosti na oporu» na 40% (r = 0,055) i umen'sheniyu latentnogo vremeni v teste «Vodnyj labirint Morrisa» na 17,6% (r = 0,08) po sravneniyu s kontrol'noj gruppoj, ekspoziciya v techenie 60 min — v 2 raza (r = 0,01) i na 44,4% (r = 0,04), v techenie 120 min — tozhe v 2 raza (r = 0,01) v oboih testah sootvetstvenno. Sdelan vyvod, chto ingalyaciya ksenona 0,5 MAK pri ekspozicii 30 min ne privodit k znachitel'nomu uluchsheniyu sostoyaniya zhivotnyh i ih sposobnosti k obucheniyu, o chem svidetel'stvuet otsutstvie statisticheski znachimyh razlichij. Ekspoziciya zhe ksenona v techenie 60 min znachitel'no umen'shaet nevrologicheskij i kognitivnyj deficit v gruppe issledovaniya, a uvelichenie vremeni ekspozicii ksenona do 120 min okazyvaet sopostavimyj effekt.

The relevance of the problem of ischemic stroke is difficult to overvalue in modern terms. The data on the frequency of occurrence and outcomes, especially among young people, force us to look for new strategies to minimize its consequences. Recent experimental studies have shown pronounced neurocardio-nephroprotective properties of lithium salts.Aim of study. To evaluate the effect of lithium chloride on the lethality and severity of cognitive and neurological deficits in the modeling of ischemic stroke in rats.Materials and methods. The study used mongrel male rats weighing 312±12.5 g. The model of Longa’s focal ischemia was used as a basis. The animals were divided into 5 groups: false-operated, control (model of ischemic stroke with the introduction of 0.9% NaCl) and three groups with the introduction of lithium chloride in various concentrations (4.2 mg/kg, 21 mg/kg and 63 mg/kg). The drug was administered daily for 14 days with a parallel assessment of neurological deficits.Results. According to the results of the experiment, the following data were obtained with respect to lethality in the studied groups: false — operated 0 out of 8, control group — 13 out of 22 (lethality 59%), group 3 (LiCl 4.2 mg/kg) — 8 out of 14 (lethality 57%), p>0.05 with respect to control, group 4 (LiCl 21 mg/kg) — 6 out of 15 (lethality 40%) p>0.05 with respect to control and in group 5 (LiCl 63 mg/kg) — 4 out of 15 animals died (lethality 27%) p=0.0317. Lithium chloride at doses of 21 mg/kg and 63 mg/kg resulted in a decrease in the severity of neurological deficits on the second day of the experiment. On the 15th day of the experiment, there were no differences in the severity of neurological disorders. Also, the dosage of 63 mg/kg contributed to better memory retention during the assessment of cognitive functions.Conclusion. Lithium chloride at a dosage of 63 mg/kg significantly (p=0.037) reduced the mortality and severity of neurological deficits in the simulation of experimental ischemic stroke in rats compared to the control group.

The majority of stroke patients have cognitive symptoms and about 50% of them live with neurological deficits that critically limit social adaptation capacities even in the absence of significant motor impairments. The aim of this study was to select the optimal length of 0.5 MAC xenon exposure in order to alleviate the neurological and cognitive impairments in experimental stroke. The focal ischemia-reperfusion injury was modeled in rats (n = 70) ising Longa method. The intervention was immediately followed by inhalation of 0.5 MAC xenon for 30, 60 or 120 min. The neurological deficit was assessed using a 'Limb placement' seven-test battery and the cognitive functionalities were assessed by the Morris water maze test. A 30 min 0.5 MAC xenon exposure provided a 40% increase in the limb placement scores and a 17.6% decrease in the Morris water maze test latency compared with the control group (р = 0.055 and р = 0.08, respectively). With a longer 60 min exposure, the trends became significant, the scores improving 2-fold and by 44.4% compared with the control group (р = 0.01 and р = 0.04, respectively), whereas 120 min exposures afforded 2-fold improvements in both tests (р = 0.01). We conclude that, although 30 min post-stroke inhalations provide negligible benefits in terms of neurological status and learning capacity, prolonged exposure times of 60–120 min afford significant improvement in neurological and cognitive indicators and largely alleviate the deteriorating ischemic damage.

Дисрегуляция артериального давления вносит значительный вклад в течение и исход сепсиса. Одним из генов, влияющих на состояние сосудистой стенки, эндотелий и тонус артериол, является ген рецептора 1 к ангиотензину II (AGTR1). Поэтому целью нашей работы являлось определение вклада в течение и исход сепсиса генетического полиморфизма AGTR1 rs275651. В исследование были включены пациенты ОРИТ (отделения реанимации и интенсивной терапии), n=286, трех ГКБ (городских клинических больниц) в возрасте 18-92 лет с сепсисом. В общей группе (n=286) септических пациентов наблюдалась разница по частоте развития септического шока в зависимости от генотипа AGTR1 rs275651. У носителей генотипа AGTR1 TT реже развивался септический шок по сравнению с пациентами генотипов AGTR1 AT, AA (60% против 73%, р=0,47, ТМФ (точный метод Фишера), OR=1,8, 95% CI: 1,1-3,3). В подгруппе пациентов с сахарным диабетом второго типа (n=79) были выявлены различия в летальности. Так, носители генотипа TT AGTR1 rs275651 характеризовались меньшим уровнем летальности по сравнению с носителями генотипов ТA, AA (60% против 88%, р=0,018, OR=5,0, 95% CI: 1,34-18,9, ТМФ). Частота развития септического шока у носителей более распространенного генотипа AGTR1 TT также была ниже в подгруппе пациентов с диабетом (57% против 92%; p=0,02, OR=9,2 95% CI: 1,97-42,9, ТМФ). Таким образом, полиморфные варианты промоторной области гена AGTR1 влияют на частоту развития септического шока, а также на течение и исход сепсиса у пациентов с сахарным диабетом. Dysregulation of blood pressure significantly impacts the course and outcome of sepsis. The AGTR1 gene encodes angiotensin II receptor type 1, which affects the vascular tone and contributes to septic shock. Our study aims to define whether the AGTR1 polymorphism contributes to the course and outcome of sepsis. The study included patients (n=286) from three ICU (Intensive Care Unit) aged 18-92 years with sepsis. In all patients (n=286) with sepsis the incidence of septic shock differed depending on AGTR1 genotype: carriers of the AGTR1 TT genotype had a less incidence of septic shock compared with patients with the AGTR1 AT, AA genotypes (60% vs. 73%, P = 0.47, FET (Fisher`s Exact Test), OR=1.8, 95% CI: 1.1-3.3). In group of patients with diabetes mellitus (n=79), we also found differences in sepsis course and outcome based on the AGTR1 rs275651 genotypes. The subgroup of TT AGTR1 rs275651 genotype carriers demonstrated significantly lower mortality compared with TA, AA genotypes carriers (60 % vs. 88 %, Р=0,018, OR=5,0, 95% CI: 1,34 -18,9, FET). The incidence of septic shock was also less in AGTR1 TT genotype-carriers in subgroup patients with diabetes (57% vs 92%, P=0,02, OR=9,2, 95 % CI: 1.97-42.9, FET). We found an association of the functional polymorphism AGTR1 rs275651 with course and outcome of sepsis in ICU patients with diabetes mellitus: carriers of the more common TT genotype had less incidence of septic shock and lower mortality compared to carriers of the minor A allele.

Введение. В современном мире проблема инсультов постепенно выходит на лидирующие позиции. Отсутствие эффективных медикаментозных методов коррекции острого нарушения мозгового кровообращения приводит к необходимости поиска новых препаратов с нейропротекторным потенциалом, способных если не предотвратить, то значимо минимизировать последствия и тяжесть ишемического инсульта. Цель исследования - оценка влияния различных доз хлорида лития на фосфорилирование GSK-3β и выживаемость животных на модели ишемического инсульта. Методика. В исследовании были использованы беспородные крысы - самцы, разделённые на 5 групп: ложнооперированные (n=9), контрольная группа (ишемический инсульт с введением раствора NaCl 0,9% в объеме, эквивалентном вводимым лекарственным средствам в других группах, n=5), и группы с введением хлорида лития в дозах 4,2 мг/кг (n=5), 21 мг/кг (n=5) и 63 мг/кг (n=5). Ишемический инсульт моделировали по методу Лонга. По истечении 7 сут от начала эксперимента животные подвергались гуманной эвтаназии с извлечением головного мозга и дальнейшим определением уровня фосфорилированной формы GSK-3β (p-GSK-3β) методом вестерн-блоттинга. Нейропротекторный эффект солей лития реализуется благодаря прямому ингибированию ключевой киназы аптотического механизма клеточной сигнализации - гликоген-синтазы киназы-3β (GSK-3β) с переводом её в фосфорилированую форму (p-GSK-3β). На 7-е сут также был проведен анализ показателей летальности в группах. Для множественных сравнений рассчитывали критический уровень значимости при использовании поправки Бонферрони. Результат. Хлорид лития в дозе 4,2 мг/кг оказывал минимальное влияние как на уровень p-GSK-3β (p=0,8), так и на летальность по отношению к контрольной группе (p>0,017). Доза 21 мг/кг, в свою очередь, значимо повышала уровень p-GSK-3β (p=0,008), но не снижала летальность (p>0,017) по отношению к группе контроля. При использовании дозировки 63 мг/кг уровень p-GSK-3β был максимально приближен к группе ложнооперированных животных (p=0,007), а летальность на 7 сут была значимо ниже (p>0,017). Заключение. Хлорид лития обладает отчётливым дозозависимым нейропротекторным эффектом. Нейропротекторный эффект солей лития реализуется благодаря прямому ингибированию ключевой киназы аптотического механизма клеточной сигнализации - гликоген-синтазы киназы-3β (GSK-3β) с переводом её в фосфорилированую форму (p-GSK-3β) Реализация нейропротекторного эффекта данного препарата потенциально способна улучшить прогнозы течения ишемического инсульта. Background. Ischemic stroke is becoming a major medical concern worldwide. Reasons for this include the aging population, which experiences an increasing frequency of cardiovascular problems. Additionally, social factors, e.g., smoking, fatigue, substance abuse, lead to strokes in young and middle-aged people. The lack of effective medical methods for correcting acute cerebral circulatory disorders underscores the need for new drugs whose neuroprotective potential can prevent or significantly minimize the consequences and severity of ischemic stroke. Aim. To evaluate the effect of different doses of lithium chloride on GSK-3ß phosphorylation and on animal survival in a model of ischemic stroke. Methods. 29 male rats were divided into five groups: Sham-operated (n=9); control, ischemic stroke with administration of a volume of 0.9% NaCl solution equivalent to the volume of the administered drugs in other groups (n=5); and groups with administration of lithium chloride at doses of 4.2 mg/kg (n=5), 21 mg/kg (n=5), and 63 mg/kg (n=5). Ischemic stroke was produced by the Long method. After 7 days, the animals were subjected to humane euthanasia. The brain was excised, and the phosphorylated form of GSK-3β (p-GSK-3β) was measured by Western blotting. The neuroprotective effect of lithium salts occurs due to a direct inhibition of the key kinase of the apoptotic mechanism of cell signaling, glycogen-synthase kinase (GSK-3β), that is transformed into a phosphorylated form. Also, the group mortality rates were analyzed on day 7. For multiple comparisons, a critical level of significance was calculated using the Bonferroni correction. Results. Lithium chloride, 4.2 mg/kg, had a minimal effect on both p-GSK-3ß (p=0.8) and mortality compared to the control group (p>0.017). A dose of 21 mg/kg significantly increased p-GSK-3ß (p=0.008), but did not reduce mortality (p>0.017), relative to the control group. At a dose of 63 mg/kg, p-GSK-3ß was similar to that of the sham operated animals (p=0.007), and the mortality on day 7 was significantly lower (p>0.017). Conclusion. Lithium chloride produces a dose-dependent, neuroprotective effect. This protective effect occurs due to a direct inhibition of the key kinase of the apoptotic mechanism of cell signaling, glycogen-synthase kinase (GSK-3β), that is transformed into a phosphorylated form. This neuroprotection is potentially able to improve the prognosis of ischemic stroke.

Currently, a number of experimental studies have demonstrated compelling evidence of neuro-, cardio-, and nephroprotective properties of medications containing lithium chloride.Aim of the study. To evaluate the effect of various concentrations of lithium chloride on ischemic stroke volume and perifocal edema in rats after cerebral ischemia.Material and methods. Male mongrel rats weighing 315±13.5 g were used in the study. The focal ischemia model according to Longa et al. was employed. The animals (n=35) were divided into 5 groups: sham-operated, control group (ischemic stroke model with NaCl 0.9% administration) and three groups who received lithium chloride in different concentrations (4.2 mg/kg, 21 mg/kg and 63 mg/kg). Lithium chloride was administered immediately after cessation of middle cerebral artery occlusion and then every 24 h until euthanasia. To assess the degree of brain damage, the animals underwent magnetic resonance imaging (MRI) on day 2, and brain sections stained with 2,3,5-triphenyltetrazolium chloride were evaluated after euthanasia on day 7. Intergroup differences were assessed using the Mann-Whitney criterion.Results. According to MRI data, lithium chloride at a dose of 4.2 mg/kg had no significant effect on ischemic stroke volume and perifocal edema versus the control group on day 2 (P=0.9). With lithium chloride at 21 mg/kg, stroke volume and perifocal edema were significantly lower than in the control group (by 25%, P=0.04 and 18%, P=0.03, respectively). Lithium chloride at a dose of 63 mg/kg was more likely to reduce stroke volume (by 45%, P=0.004) and perifocal edema (by 35%, P=0.007). When determining lesion volume on day 7, the data were comparable to those obtained on day 2. With the 21 mg/kg dose, stroke volume was 20% lower than in the control group (P=0.04). Lithium chloride, 63 mg/kg, reduced stroke volume by 40% (P=0.004).Conclusion. Lithium chloride dose affects necrotic focus formation and manifestations of perifocal cerebral edema after middle cerebral artery occlusion. The maximum reduction in the volume of ischemic stroke and perifocal edema was observed when the 63 mg/kg dose was used.