Genetic predisposition partially accounts for the clinical variability of the course of an infectious process. A total of 750 people, including 419 (81.1%) male patients aged 42.9±0.9 years, admitted to the clinics of the V. A. Negovsky Research Institute of General Reanimatology (Moscow, Russia), were genotyped to establish the influence of genetic factors on their susceptibility to critical conditions. Materials and methods. Tetra-primer allele-specific polymerase chain reaction was used to investigate single-nucleotide polymorphisms (SNP) in the xenobiotic detoxification and oxidative stress genes (CYP1A1 (three sites), AhR, ABCB1, SOD2, GCLC and CAT) and in the vascular homeostasis genes (ACE, AGT, AGTR1, NOS3, VEGFα and MTHFR). Results. A total of 268 nosocomial pneumonia (NP) cases were registered in a patient group. Individual SNP analysis has shown that among the patients with NP the risk of acute respiratory distress syndrome (ARDS) is associated with the carriage of the following genotypes: CYP1A1 rs2606345-Т/Т (p=0.0027, OR=2.38; 95% CI: 1.35—4.17) and AhRrs2066853-G/A-A/A (p=0.0012, OR=2.94; 95% CI: 1.54—5.60). The frequency of the C allele of the AGTR1 gene (re5186) was much higher among the survivors (in the NP group). The assessment of a multiplicative genetic model of genes that had demonstrated the highest single-locus effects because of a ARDS risk, as well as in-hospital mortality, could establish the complex genotype including a combination of risky alleles of the detoxi- fication and vascular homeostasis genes (CYP1A1 rs2606345-T — AhR rs2066853-A and ACE rs4340-D — AGT rs699-C — AGTR1 rs5186-C), which was associated with the increased risk of both NP and ARDS, as well as with the likelihood of a fatal outcome. Conclusion. An understanding of the risk factors of NP and ARDS will aid in predicting the outcome of the underlying disease and in developing possible preventive measures.

The success of the treatment of a patient depends on the proper identification of the pathological process and its complications on time. The procedure of the diagnostics is carried out accord� ing to a nosological principle, which is the basic principle of medicine. The other basic principles are also to be taken into account during the procedure of the verification of a certain pathological processes. First, it is necessary to determine the origin of the pathological process and the class it belongs to in accordance with the international classification of diseases (cardiovascular diseases, respiratory diseases, cancerous dis� eases, infectious disease etc.).The most important require� ment for diagnosis is identification of the etiology of the dis� ease. For example, in case of an infectious disease this determines the accuracy of the diagnosis and subsequent ade� quate antibiotic therapy. One of the main basic principles is pathogenetic. The pathogenesis (mechanisms of develop� ment) of the disease is a kind of pathologic process. The pathologic process of inflammation is a basis of infectious dis� eases and infectious complications. A necessary requirement

The problem of predicting the development and outcomes of acute respiratory distress syndrome (ARDS) remains to be solved. Objective: to estimate the informative value of the plasma levels of surfactant protein A (SP2A) as a prognostic biomarker for the development and outcome of ARDS in patients with severe pyoseptic complications in critical conditions. Subjects and methods. This investigation was conducted at the Research Institute of General Reanimatology (RIGR), Russian Academy of Medical Sciences, in 2010—2012. It enrolled 80 patients (including 25 analyzed ones) in accordance with the inclusion and exclusion criteria, as well as 30 apparently healthy donors. ARDS and its stages were diagnosed using the RIGR criteria. Plasma SP2A levels were determined by enzyme immunoassay using a Human Surfactant Protein A ELISA, RD191139200R kit (BioVendor, USA). The findings were statistically analyzed using a Statistica 7.0 package.Sensitivity and specificity of SP2A testing were determined by ROC analysis. The difference between groups at pResults. In patients with ARDS plasma SP2A level was higher than in those without ARDS within the whole study independing on a day of testing. There were no significant dif2 ferences between plasma SP2A levels in the patients with Stages 1 and 2 ARDS. On day 1, the plasma SP2A content of 24.5 ng/ml had a sensitivity of 60.0% and a specificity of 85.7% in predicting the development of ARDS on days 4—5 of intensive care unit admission (the area under the curve 0.74; 95% confidence interval, 0.527—0.872; p=0.0031). On study day 1, the SP2A level of 38.8 ng/ml had a sensitivity of 65.0% and a specificity of 80.0% in predicting a fatal outcome in patients with ARDS (the area under curve 0.74; 95% confidence interval, 0.577—0.866; p=0.0026). Conclusion. On a day when a severe pyoseptic complication was diagnosed, the SP2A level of 24.5 ng/ml served as a sensitive and specific prognostic biomarker for the development of ARDS on days 4—5 of an intensive care unit stay. Within the first 24 hours (on the day when ARDS was diagnosed), the plasma SP2A content of 38.8 ng/ml was a sensitive and specific prognostic biomarker for death prediction in ARDS. Key words: acute respiratory distress syndrome, surfactant protein A, biomarker, prediction, outcomes.

Objective: to study the clinical efficiency of undifferentiated and differentiated use of escalation and de-escalation procedures for optimizing positive end-expiratory pressure (PEEP) during mechanical ventilation in patients with acute respiratory distress syndrome (ARDS) resulting from direct and indirect damaging factors. Subjects and methods. During a prospective study, 24 examined patients (16 men, 8 women; their age was 22 to 65 years) with ARDS of different genesis were divided into 2 groups. Group A (n=11; 7 men, 4 women) and Group B (n=13; 9 men, 4 women) included patients with ARDS arising from both direct (gastric content aspiration, blunt chest injury with lung contusion, and acute bilateral bacterial pneumonia) and indirect (abdominal sepsis, severe nonthoracic injury, and acute massive blood loss) damaging factors. The results of treatment via differentiated or undifferentiated, according to the cause of ARDS, use of escalation and de-escalation procedures for PEEP optimization were assessed in Groups A and B patients. Results. The differentiated, according to the cause of ARDS, use of escalation and de-escalation procedures for PEEP optimization makes it possible to more effectively improve the parameters of pulmonary gas exchange and biomechanics and to reduce the length of respiratory support and stay in the intensive care unit, the incidence of ventilator-associated pneumonia, and mortality rates in patients with ARDS resulting from direct and indirect damaging factors. Conclusion. It is advisable to apply the differentiated, according to the cause of ARDS, approach to choosing escalation or de-escalation procedures to optimize PEEP in patients with ARDS of different genesis. Key words: acute respiratory distress syndrome, direct damaging factors, indirect damaging factors, mechanical ventilation, positive end-expiratory pressure, escalation PEEP optimization procedure, de-escalation PEEP optimization procedure, lung opening manoeuver.

The review presents the current view of the etiology and pathogenesis of hormonal and metabolic changes in critically ill patients. To build up a system accessible to clinicians to establish an early diagnosis of hypermetabolism syndrome will be able to make differential correction of endocrine and metabolic disorders until decompensated multiple organ failure develops. Key words: critical condition, metabolism, hypercatabolism, somatotropin, insulin-like growth factor.

The review article deals with the problem of ischemic preconditioning, the universal physiological mechanism of cell protection from hypoxia. Preconditioning is the term used to describe a phenomenon of the enhanced tolerance of a cell to a damaging factor due to its preliminary effects of stressful stimuli. The article describes the phenomenon of ischemic preconditioning and summarizes the results of a study of the possible mechanisms of this effect in organs and tissues. It discusses the key role of the enzyme glycogen synthase 3fl in the regulation of the mitochondrial pore and that of the latter in the protection of a cell from hypoxia. Experimental data are given on the testing of different drugs as pharmacological agents that initiate/inhibit preconditioning. Reasons for the selective efficacy of some antihypoxants and antioxidants are analyzed in the context of the ischemic preconditioning theory. Conventional anesthetics and analgesics as potential inductors or inhibitors of the process in question are discussed. Key words: ischemic preconditioning, hypoxia, anesthetics, cyto-protection.

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 study the production of surfactant apoprotein D in preterm neonates with acute respiratory distress syndrome (ARDS) during artificial ventilation (AV). Subjects and methods. The paper presents the results of studying the production of surfactant protein D (SP-D) in various biological fluids in 44 preterm neonates. Two groups of newborn infants were identified according to the clinical manifestations of ARDS. The study group comprised 25 infants with the severe course of the disease, in this connection the preventive administration of the exogenous surfactant Curosurf and AV were made in all the neonates at birth. The control group included 19 preterm babies without signs of ARDS. Results. The study has demonstrated that in parturients and preterm neonatal infants, surfactant apoprotein D is detectable in various biological fluids: amniotic fluid, the gastric aspirate obtained just after birth, residual umbilical cord blood, serum following 8 hours of birth, and bronchoalveolar fluid. Despite the low gestational age of the neonates, the lung surfactant system is able to produce SP-D, as evidenced by its high content in the amniotic fluid and residual umbilical cord blood of preterm neonates. The production of apoprotein D in preterm neonates considerably reduces in the next few hours after birth. Conclusion. The findings suggest that fetal tissues generate SP-D, which improves pulmonary gas exchange in preterm neonates in the first hours after birth and that alveolar-capillary membrane dysfunctions are transient in the neonates on AV. Key words: preterm neonates, acute respiratory distress syndrome, surfactant, surfactant apoprotein D.

Objective: to study whether posthypoxic brain dysfunctions may be corrected by low-intensity laser irradiation an hour after hypovolemic hypotension at late postresuscitation stages (following 30 days). Material and methods. Experiments were carried out on high-anxious male albino rats weighing 280—300 g. The study model was one-hour hypovolemic hypotension (blood pressure 40 mm Hg), followed by blood reinfusion. The integrative brain function was evaluated from the indices of the rat orientative-trying behavior in the elevated cross labyrinth test. The depressive component of the rats’ behavior was examined in the forced swimming test. Plasma norepinephrine levels were measured. Laser irradiation was performed 30 days after blood reinfusion. Results. Laser irradiation used at late postresuscitation stages leads to the normalization of plasma norepinephrine levels, the reduction of anxiety in the rats, and their improved orientative-trying behavior. Conclusion. The positive impact of laser irradiation on the rat orientative-trying behavior is associated with its anxiolytic effect, in which the recovery of autonomic homeostasis plays a considerable role. Key words: blood loss, postresuscitative period, behavior, laser, posthypoxic encephalopathy, norepinephrine.

Objective: to determine the optimum alveolar opening parameters for the improvement of postoperative pulmonary oxygenizing function in patients with a left ventricular ejection fraction (LVEF) of less or more than 40% after aortocoronary bypass surgery (ACBS). Subjects and methods. Twenty patients with a LVEF of less than 40% after ACBS and with postoperative pulmonary oxygenizing dysfunction (PaO2/FiO2 less than 250) (Group 1) were examined. A control group consisted of 20 patients with a LVEF of more than 40% (Group 2). Gas exchange, respiration biomechanics, and central hemodynamic (CH) parameters were monitored (a Vigilance monitor (Edvard LifeScience)). Alveolar mobilization was carried out on Drager Evita-2 apparatuses in the BIPAP mode, by taking into account the previous artificial ventilation (AV) parameters. The low pressure phase corresponded to the positive end-expiratory pressure (PEEP) with volume AV, the high pressure phase was Pplato; the duration of both phases — that of inspiration and expiration (the high pressure phase was inspiration time; the low pressure phase was expiration time). Then the values of Pplato and PEEP were simultaneously increased by 2 cm H2O with a duration of 10 breathing cycles, by continuously monitoring Vt and SaO2 over this interval. By continuously monitoring Vt, a stepwise increase in PEEP and Pplato was continued until there was a Vt reduction or a negative impact of AV on CH. All alveoli were considered to be open when the maximum Vt and SaO2 were achieved. Conclusion. In Group 1 patients with Pinsp of 27—30 cm H2O, PEEP of 10—12 cm H2O, there are increases in PaO2/FiO2 and Cst. In Group 2, the increase of PaO2/FiO2 and Cst is observed with Pinsp of 30—35 cm H2O and PEEP 12—14 cm H2O. With these AV indices, there is an allowable hemodynamic reduction that results in no negative consequences and development of cardiovascular events. After switching to AV in an individually chosen mode, all hemodynamic parameters return to the baseline level. Consequently, the proposed AV mode and ventilation parameters are safe and effective for the prevention of early postoperative respiratory failure in cardiosurgical patients. Key words: recruiting ventilation, positive end-expiratory pressure, alveolar opening.