Objective: to study associations of DNA polymorphism in acute community-acquired pneumonia (ACAP). Subjects and methods. The study enrolled 243 patients with ACAP; a control group included 178 healthy individuals. Genetic variability was investigated for the following candidate locuses: the ACE renin-angiotensin system gene, the CCR5 chemokine receptor gene and 4 xenobiotic detoxification genes (CYP1A1, CSTM1, GSTT1, and GSTP1). According to the earlier data on the effect of CYP1A1 alleles on predisposition to pneumonia, haplotypes were determined by 3 polymorphic sites of this gene. Results. Protective and predisposing geno- and haplotypes were described by the above loci and their combinations. Homozygotes for the deletion at the ACE locus (OR=1.8; p=0.013); GSTM1-pos-itive genotypes (OR=1.7; p=0.010) and homozygotes for 606T allele in the CYP1A1 gene (OR=1.6; p=0.020) were found to have a higher predisposition to pneumonia. A combination of the two latter genotypes (OR=1.9 at p=0.006; its frequency in the control was more than 20%) proved to be prognostically most effective. Conclusion: three polymorphic markers were identified in the CYP1A1, GSTM1, and ACE genes associated with the development and course of ACAP. Key words: gene polymorphism, xenobiotic detoxification genes, pneumonia.

Objective: to evaluate the efficiency of artificial ventilation (AV) after administration of the exogenous surfactants Curosurf and Surfactant BL in premature neonates with respiratory distress syndrome (RSD). Subjects and methods. The paper presents the results of evaluation of the efficiency of therapy with exogenous surfactants, by examining the blood gas composition and AV parameters. The study included 122 premature neonates with severe RSD. According to the type of a used surfactant, two groups of neonates were identified: Group 1 comprised 67 neonates who were given Curosurf and Group 2 consisted of 55 neonates who had Surfactant BL. Results. The study has revealed some differences between the drugs. Four hours after administration of Curosurf, the neonates with RSD showed heterodirectional changes in partial blood oxygen tension; no abnormal changes in this index were found in most neonates; however, hyperoxia or hypoxia appeared in some newborn infants. After administration of Surfactant BL, no hyperoxia was virtually detected. Hyperoxia did not depend on the baseline oxygen fraction in the inspired gas mixture in most cases. The found changes were transient. To choose ventilation parameters was based on an attempt to bring partial blood oxygen tension closer to the normal values. The main task of the treatment was achieved: this was to carry out sparing AV in premature neonates, allowing no mechanical injury to the immature lung or ventilation complications. Conclusion. pO2 variability after administration of exogenous surfactants calls for a considerate attitude to the choice of AV parameters and an individual approach to a patient. The specific features of the pharmacological action of exogenous surfactants should be taken into account when they are used. In this connection, blood gas composition should be frequently investigated – particularly within the first 24 hours after administration of the agents in order to timely modify AV parameters.

Objective: to search for an accessible, valid, and easy-to-use method for the diagnosis and monitoring of a neuronal lesion in severe brain injury (SBI). Subjects and methods. Thirty-three patients aged 18—55 years with isolated SBI (the Glasgow coma scores for admission consciousness were 6±2) were examined; the serum content of neuron-specific protein S-100B was further analyzed. Results and discussion. The cell damage marker concentration was substantially increased in the acute period of brain injury. When the pathological process followed a favorable course, S-100B was considerably decreased just on day 2 of the disease. When the changes were negative, S-100B concentrations remained virtually unchanged or even increased, which was indicative of secondary brain reperfusion/ischemic lesions. The mean baseline marker level varied with the type of brain injury diagnosed by computed tomography; the highest figures being noted in the groups where significant brain tissue lesion was detected. Key words: severe brain injury, prognosis, S-100B protein.

Objective: to study the time course of changes in oxidative status parameters and their relationship with inflammation mediators in the acute period of severe brain injury (SBI). Subjects and methods. One hundred and thirteen patients aged 17—67 years were examined. The injury was closed and open in 54 (47.8%) and 59 (52.2%) patients, respectively. Severe brain contusions were observed in 47 patients, diffuse axonal lesions were seen in 2, and intracranial hematomas were present in 64 patients. The Glasgow coma scores for admission consciousness loss were 6.8±0.25. A control group comprised 23 healthy individuals. The significance of differences was estimated by Student’s test, Wilcoxon-Mann-Whitney, test, Spearman’s correlation test. Venous blood samples were used to study total oxidative activity (TOA) and total antioxidative activity (TAA), diene conjugates, lactic acid, albumin, transferrin (TF), ceruloplasmin, C-reactive protein, and lactoferrin (LF) were measured in venous blood on disease days 1, 4, 7, 10, 14, and 21. The profile of plasma cytokines (IL-1j8, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, TNF-а, and IFN-y) was studied by flow fluorometry on a Cytomics FC 500 cytofluorometer (Beckman Counlter, USA) (reagents were from Bender Medsystems, Austria). Results. In SBI, there was an increase in oxidants, a reduction in antioxidant activity, and lipid peroxidation activation, which were closely related. The oxidation coefficient (TOA/TAA) was 40 times greater than the normal values on days 7 to 10. The oxidation parameters were found to be associated with inflammation and cytokine-mediated immunological reactions. The time course of changes in the study proteins was characteristic for systemic inflammation and there was an association with oxidative processes only for ceruloplasm. TF was found to have an association with IL-5 and IL-10, which reflects its involvement in immunological reactions. The association with hypoxia was established for IL-6 and LF. Ihe elevation or LF was directly caused by the neutrophil activating factor IL-8. Conclusion. Oxidative stress is an important factor in impairing hemostasis in SBI. The processes of oxidation and antioxidation are associated with inflammation and cytokine-mediated immunological reactions. Key words: severe brain injury, oxidative stress, cytokines, acute inflammation phase proteins.

Objective: to study the effect of sodium oxybutyrate on canine mesentery microcirculation and liver metabolism in hemorrhagic stroke. Materials and methods. The investigation was based on the examination of specimens taken from 72 dogs of both sexes, weight 15.5±1.5 kg. Hypovolemic hypotension was induced by free bloodletting via the femoral artery. Systolic blood pressure was lowered to 40 mm Hg and maintained at the same level during an hour by the Wiggers procedure. The magnitude of blood loss was 31—33 ml/kg. The dogs were divided into 4 groups: 1) intact (n=5); 2) one-hour hypovolemic hypotension (n=8); 3) control (n=31), in which physiological saline was intravenously injected at a concentration of 0.9—1.1 ml/kg an hour after hypovolemic hypotension; 4) experimental (n=28), in which 10% sodium oxybutyrate solution was intravenously injected at a concentration of 180—200 mg/kg an hour after hypovolemic hypotension. In Groups 1 and 2 dogs, as well as in the control and experimental groups, divided into 2 subgroups, in which laparotomy was carried out under local 0.25% novocaine solution in combination with intravenous sodium thiopental (15—20 mg/kg) an hour after the drug administration and an hour after blood reinfusion, then right liver lobe pieces were excised for histochemical and biochemical studies. In Groups 3 and 4, heparinized blood was reinfused an hour after administration of the agent. The animals were observed during an hour. In the dogs from the latter two groups, mesentery vascular microcirculation was evaluated at control time stages, by using biomicroscopy on a MBR-1 microscope-based unit. Results. Despite uncompensated blood loss, the use of sodium oxybutyrate in hemor-rhagic stroke improves microcirculation in the mesentery vessels. In the liver, it enhances the rate of reactions of oxida-tive phosphorylation and the pentose phosphate pathway, activates glucose uptake processes, prevents lactate accumulation, preserves glycogen stores, and elevates the content of high-energy phosphates. Conclusion. Administration of 10% sodium oxybutyrate solution at concentrations of 180-200 mg/kg an hour after hypovolemic hypotension prevents the progression of mesentery microcirculatory disorders and hepatic metabolic changes during the following hour of hemorrhagic stroke. Blood loss compensation during previous administration of sodium oxybutyrate promotes a fuller and more rapid recovery of mesentery microcirculation and hepatic metabolic processes in the early postresuscitative period. Key words: hemorrhagic stroke, sodium oxybutyrate, microcirculation, metabolism, liver.

Objective: to study the impact of increased inactive (N-terminal) pro-B-type natriuretic peptide (NT-proBNP) levels in cardiosurgical patients with coronary heart disease without drastically reducing left ventricular contractility on intraoperative central hemodynamics and the specific features of therapeutic measures for its stabilization. Subjects and methods. The inclusion criteria were elective surgery, age less than 70 years, a left ventricular ejection fraction of at least 30%, and no surgical complications. Sixty-one patients aged 54.6±1.2 years with a left ventricular ejection fraction of 51. 5 ± 1. 6 %. Before surgery, NT-proBNP was determined by electrochemiluminiscence («Elescys®proBNP»). Invasive hemodynamic monitoring was made with Swan-Ganz catheters. Results. The level of NT-proBNP was 13.2—3232 pg/ml. When the preperfusion values of the biomarker was more than 350 pg/ml, the magnitude of a peptide concentration increase affected that of an elevation of pulmonary artery wedge pressure (r=0.52; p=0.002) and that of a decrease in left ventricular pump coefficient (r=-0.44; p=0.01). At the end of operations, this patient group, as compared with the others, had a lower left ventricular pump coefficient (2.9±0.2 and 3.9±0.3 g/mm Hg/m2; p<0.05) and the dosages of dopamine and/or dobutamine were increased (4.3±0.3 and 3.1±0.3 ^g/kg/min; p<0.05). The degree of NT-proBNP elevations correlated with stroke volume index (r=-0.42; p=0.02), the dosages of dopamine and/or dobutamine (r=0.38; p=0.04) and epinephrine and/or norepinephrine (r=0.66; p<0.001). NT-proBNP levels of 1100 pg/ml or more was a significant predictor (p<0.0001) of extracorporeal circulation. When the level of NT-proBNP was less than 350 pg/ml, the clinical course of operations was satisfactory in 96.6%. Biomarker variations in the range of up to 350 pg/ml failed to affect cardiac pump function before and after extracorporeal circulation and the dosages of inotropic agents at the end of operations. Conclusion. The increased NT-proBNP level that characterizes B-type natriuretic peptide hypersecretion is a risk factor for cardiac dysfunction after myocardial revascularization under extracorporeal circulation. This value of the biomarker is 350 pg/ml for patients aged under 70 years with a left ventricular ejection fraction of at least 30%, the level of 1100 pg/ml or higher being a predictor of heart failure that requires assisted circulation.

Objective: to study the general regularities and pathogenetic significance of changes in primary and secondary inflammatory mediator ratios in the formation of a systemic inflammatory response in critically ill patients. Subjects and methods. Three hundred and eighty-seven critically ill inpatients from intensive care units were examined. Results. The systemic inflammatory response syndrome develops in critical conditions, which is characterized by the increased serum levels of primary (proinflammatory cytokines) and secondary (C-reactive protein, fibrinogen) inflammatory mediators, which was more substantial in infected patients. When the hyperproduction of proinflammatory cytokines was evident, there was no adequate proinflammatory response, as suggested by the negative IL-10 level changes. Correlations were established between the serum content of inflammatory mediators and the indices of external respiration function, respiration rate, and heart rate. Conclusion. The nature of changes in the quantitative (mediator concentrations) and qualitative (mediator ratio) indices enables one to estimate the intensity of a systemic inflammatory response and to predict its further progression. Key words: critical condition, systemic inflammatory response, inflammatory mediators.

Objective: to evaluate the efficiency and safety of various perioperative analgesia modes during total hip joint replacement (THR). Subjects and methods. A randomized controlled trial enrolled 90 patients who were divided into 3 groups according to the choice of a perioperative analgesia mode on day 1: general sevofluorane anesthesia, by switching to intravenous patient-controlled analgesia with fentanyl (PCA, GA group), a combination of general and spinal bupiva-caine anesthesia, by switching to PCA with fentanyl (SA group), a combination of general and epidural ropivacaine anesthesia with continuous postoperative epidural ropivacaine infusion (EA group). All the patients received non-opi-oid analgesics after surgery. Results. Prolonged epidural block ensures better postoperative analgesia at rest and during mobilization and a less need for opioids than other analgesia modes (p<0.05). With neuroaxial block, the preoperative need for sympatomimetics is much higher than that in the GA group (p<0.05). There is also a trend toward a higher incidence of cardiac arrhythmias and postoperative nausea and vomiting in the SA and EA groups. There are no differences in the frequency of hemotransfusion and postoperative complications and the length of hospital stay. Conclusion. Prolonged epidural block provides excellent perioperative analgesia during THR, but the risk-benefit ratio needs to be carefully assessed when an analgesia mode is chosen.

Objective: to modify initial sevorane anesthesia so that the incidence of excitement and apnoea should be reduced. Subjects and methods. Seven hundred and sixty-three patients were examined and divided into 4 groups: total intravenous anesthesia (TIA) with propofol and fentanyl and 3 inhalational sevorane-based anesthesia modes; one of them was modified by the authors. Initial anesthesia modes were compared by the following criteria: the time of consciousness loss (sec); that of creating the favorable conditions for laryngeal mask airway instillation (sec); the incidence of apnoea (% of the number of patients in this group); the duration of assisted ventilation (sec); excitement (% of the number of patients in this group); cough (% of the number of patients in this group). Results. The use of sevorane excludes the need for successive induction or breathing circuit prefilling. However, initial sevorane anesthesia is somewhat longer than intravenous induction with propofol and fentanyl and is more frequently accompanied by episodes of excitement, although the latter is insignificant. TIA in turn results in the development of apnoea more frequently, which is undesirable if anesthesia with preserved spontaneous breathing is to be further performed. The use of the subnarcotic doses of propofol (0.5 mg/kg) and fentanyl (50-^g bolus) during inhalation induction permits excitement to be prevented and a patient’s spontaneous breathing to be maintained. TIA modes and the authors’ modified inhalation induction procedure are comparable in the time of falling asleep and creating the optimal conditions for laryngeal mask airway instillation. Key words: inhalational anesthesia, sevofluorane, induction.

Objective: to study the mechanisms responsible for the deposition of fluid and toxins in severe surgical endotoxicosis. Materials and methods. The reasons for triggering the mechanisms of deposition of fluid and toxins were clarified in an experimental study on animals (10 dogs) that were divided into 2 groups. All the animals were daily monitored for blood and central lymph toxicities, total circulating blood volumes, and body weight changes during natural (Group 1) and accelerated (Group 2) lymphokinesis. Whether the interstitium could be unloaded from deposited fluid and toxins was investigated in 56 patients with severe endotoxicosis. Results. In severe surgical endotoxicoses, fluid and toxins are deposited in the first days of the disease. The main reason for triggering the mechanism of deposition is the level of toxemia. The depositing process proceeds in two stages. Thoracic duct cannulation with external lymph drainage is the most effective way of unloading the interstitium from fluid and toxins. Key words: endotoxicosis, toxin deposition, interstitial space.

The authors draw attention to the fact that complete cardiopulmonary bypass can be made in the emergency situation in order to perform an extracorporeal membrane oxygenation (ECMO) procedure in a 5-year-old boy weighing 15 kg, diagnosed as having Fallot tetrad. By taking into account the technological features of the system for ECMO, there is an additional need for a blood cell separator to be applied.

Objective: to evaluate the efficacy of mexicor used to protect cardiac metabolism in patients with myocardial infarction during thrombolytic therapy with streptokinase. Subjects and methods. Fifty-four patients (mean age 51.2±5.5 years) with myocardial infarction, who underwent thrombolytic therapy with streptokinase from 30 minutes to 2 hours after the onset of the disease, were examined and cured. During the basic treatment, 28 patients received the mexicor regimen: 5—6 mg/kg intravenously before thrombolysis, then 50 mg/day as continuous infusions for 3 days with its further use as 200-mg capsules thrice daily until they were discharged from hospital. The time course of changes in £ST, the parameters of cardiac hemodynamics, systemic circulation, the activities of creatine phosphokinase-MB and malondi-aldehyde, and the values of the antioxidant system were analyzed during and after thrombolysis. Results. It was established that after administration of mexicor, the patients showed a less pronounced tendency for hypodynamic circulation and postinfarction left ventricular dilatation at the thrombolytic stages and in the postperfusion period. The frequency of high-grade reperfusion arrhythmias (after B. Lown) was 2.18-fold less and the rate of ST-segment isoelectric line achievement was higher. During hospital mexicor treatment, the frequency of heart failure and postinfarct angina pectoris episodes was decreased from 30.8 to 17.7% and from 19.2 to 10.7%, respectively; recurrent infarctions occurred 2.68-fold less frequently. Conclusion. The use of mexicor during thrombolytic therapy for myocardial infarction promotes cardiac metabolic protection during and after thrombolysis. Administration of mexicor results in a more complete recovery of cardiovascular function, cardiac hemodynamics, and metabolism in patients after thrombolysis and favors a reduction in the number of disease complications in the hospital treatment stage. Key words: myocardial infarction, thrombolysis, reperfusion, mexicor, streptokinase.

Objective: to comparatively evaluate the efficiency of tracheostomy by various methods in different artificial ventilation periods in patients with multiple organ dysfunction after cardiosurgical intervention. Subjects and methods. In the first stage, the patients in whom tracheostomy was performed in a classical surgical manner (a control group; n=15) not earlier than 7 days after arterial ventilation (AV) were compared. A study group comprised 19 patients in whom tracheostomy was carried out on days 3—4 after AV. In the second stage of the study, tracheostomy was made not later than 4 days following AV: by the puncture-dilatation method in study group 2 (n=28) and by the classical surgical procedure in control group 2 (n=49). Results. The time and procedures of an intervention were found to have an impact on the bacteriological profile of a patient, the duration of switch to spontaneous respiration, and the tracheobronchial tree. The advantages and disadvantages of the puncture-dilatation technique of tracheostomy were noted from the standpoint of hemodynamics, gas transport, possible complications, and long-term Results. Conclusion. Early tracheostomy caused a reduction in the number of infectious complications of the tracheobronchial tree, early decannulation with switch to spontaneous breathing. The puncture-dilatation procedure of tracheostomy is characterized by the minimum hypoxic period at cannula installation and ensures prompt healing in the absence of purulent complications. The classical surgical tracheostomy remains to be the method of choice during massive anticoagulant therapy. The accumulation of long-term results should be continued. Key words: tracheostomy, multiple organ dysfunction, cardiac surgery.

The review describes the role of a change in the morphofunctional properties of red blood cells in the pathogenesis of severe concomitant injury, sepsis, and acute respiratory distress syndrome. The authors give data on the nonspecific mechanisms responsible for the provision and maintenance of oxygen transport at the microvascular level. Furthermore, the review summarizes the results of recent studies dealing with the contribution of microrheological disorders to the development of organ dysfunction in sepsis and other critical conditions. Whether microrheological disorders can be corrected is also considered. Key words: critical conditions, erythrocyte deformability, erythrocyte aggregation, perftoran, infusion therapy.

By analyzing the data available in the Russian and foreign literature and their many years’ experience, the authors review the state-of-the-art of the problem associated with ventilator-associated pneumonia in intensive care units. The etiology, epidemiology, and pathogenesis of ventilator-associated pneumonia, the possibilities and limitations of its prevention and diagnostic methods, successes and difficulties and treatment of this pathology are described in detail.