The authors consider the role of genetic studies in modern medicine. The high death rates due to critical conditions (sepsis, multiple organ dysfunction, acute respiratory distress syndrome, nosocomial infections) initiate a search for prognostic models. The paper presents the results of the investigations made at the V.A. Negovsky Research Institute of General Reanimatology jointly with the V. N. Vavilov Institute of General Genetics. The panel of genetic markers, which is associated with the increased risk of both community-associated and nosocomial pneumonia (combinations of polymorphic variants in the xenobiotic detoxification gene (CYP1A1), cytokines (IL-6), and renin-angiotensin-converting enzyme (ACE), has been revealed. Genetic factors are essential in determining a response to drugs; 20—95% of the individual variability in the efficiency of their metabolism has been ascertained to result from genetic variability. An associative study has revealed differences in the efficiency of antibacterial therapy in terms of the GSTP1 and ABCB1 genes. Thus, it can be said that the possibilities of molecular genetic methods open prospects for developing the new area in reanimatology — critical care genetics. Identification of groups at increased risk for life-threatening conditions is particularly important in preventing their development and detecting their early markers for the timely determination of the required volume of specialized medical care. Key words: multifactorial diseases, gene polymorphism, xenobiotic detoxification genes, community-associated pneumonia, nosocomial pneumonia.

Objective: to improve treatment results in miners, by studying the specific features of the course of their critical conditions caused by severe traumatic injuries, and to develop differentiated intensive therapeutic regimens for detected abnormalities. Subjects and methods. A total of 1107 subjects were examined during the study. Central hemodynamic function was explored in 371 healthy miners with various lengths of underground mining; a control group included 30 healthy volunteers unexposed to occupational hazards. Examinations were made in 386 severe brain injury victims, including 218 victims with no length of underground work and 115 injured miners with an underground work length of more than 5 years. A control group comprised 53 apparently healthy donors. One hundred and twenty-two miners with severe thermal injury were examined. A control group consisted of 39 apparently healthy volunteers. One hundred and six victims with acute respiratory distress syndrome in the presence of severe concomitant injury were examined under mechanical ventilation. Sixty-three injured miners formed a study group; a comparison group included 43 subjects with no length of underground mining. Conclusion. Upon longer exposure to occupational hazards, the prenosological changes occur in the miners' organs and systems, which display a regular phasic pattern, fit in the picture of general adjustment syndrome, and determine the specific features of critical conditions. The peculiarities of the critical conditions caused by severe traumatic injuries in miners are the early development and high frequency of complications, the more severe course and late recovery of the body's lost functions, unlike the victims unexposed to occupational hazards. Differentiated intensive therapy for critical conditions in miners with severe traumatic injuries makes it possible to improve treatment results and to reduce death rates. 

Acute respiratory distress syndrome (ARDS) is a common complication of many diseases. Its polyetiological pattern determines the specific features of lung morphological changes and the clinical course of ARDS. Objective: to analyze the pathogenesis of ARDS in the context of the general pathological processes underlying its development. Material and methods. More than 200 lungs from the people who had died from severe concomitant injury or ARDS-complicated pneumonia were investigated. More than 150 rat experiments simulated various types of lung injury: ventilator-induced lung injury with different ventilation parameters; reperfusion injuries (systemic circulation blockade due to 12-minute vascular fascicle ligation, followed by the recovery of cardiac performance and breathing); microcirculatory disorder (injection of a thromboplastin solution into the jugular vein); blood loss; betaine-pepsin aspiration; and closed chest injury. Different parts of the right and left lungs were histologically examined 1 and 3 hours and 1 and 3 days after initiation of the experiment. Lung pieces were fixed in 10% neutral formalin solution and embedded in paraffin. Histological sections were stained with hematoxylin and eosin and using the van Gieson and Weigert procedures; the Schiff test was used. Results. The influence of aggression factors (trauma, blood loss, aspiration, infection, etc.) results in damage to the lung and particularly air-blood barrier structures (endothelium, alveolar epithelium, their basement membrane). In turn the alteration of cellular and extracellular structures is followed by the increased permeability of hemomicrocirculatory bed vessels, leading to the development of non-cardiogenic (interstitial, alveolar) pulmonary edema that is a central component in the pathogenesis of ARDS. Conclusion. The diagnosis of the early manifestations of ARDS must account for the nature of an aggression factor, the signs confirming the alteration of the lung and particularly air-blood barrier structures, pulmonary oxygenizing dysfunction, the development of noncardiogenic pulmonary edema; the absence of left ventricular failure signs. Key words: acute respiratory distress syndrome, pathogenesis.

to improve treatment results in premature infants with neonatal respiratory distress syndrome (NRDS), by establishing developmental mechanisms and elaborating methods for its early diagnosis, treatment, and prevention. Material and methods. The paper analyzes the results of a clinical observation and laboratory, instrumental, immunological, morphological, and radiological studies of 320 premature neonates at 26—35 weeks gestational age. The following groups of neonates were identified: 1) 40 premature neonatal infants without NRDS and with the physiological course of an early neonatal period (a comparison group); 2) 190 premature neonates with severe NRDS in whom the efficiency of therapy with exogenous surfactants, such as surfactant BL versus curosurf, was evaluated; 3) 90 premature newborn infants who had died from NRDS at its different stages. Results. The poor maternal somatic, obstetric, and gynecological histories in the early periods of the current pregnancy create prerequisites for its termination, favor the development of severe acute gestosis, and cause abnormal placental changes. Each gestational age is marked by certain placental changes that promote impaired uterineplacentalfetal blood flow and premature birth. Alveolar and bronchial epithelial damages, including those ante and intranatally, microcircula tory disorders play a leading role in the tanatogenesis of NRDS. Intranatal hypoxia and amniotic fluid aspiration are one of the important factors contributing to alveolar epithelial damage and NRDS in premature neonates. Exogenous surfactants prevent the development of hyaline membranes and are useful in the normalization of ventilation-perfusion relationships and lung biomechanical properties. Conclusion. This study could improve the diagnosis and treatment of NRDS, which assisted in reducing the duration of mechanical ventilation from 130±7.6 to 65±11.6 hours, the number of complications (the incidence of intragastric hemorrhages decreased from 28.8 to 9%), the stay length of the neonates in an intensive care unit, and early neonatal mortality rates from 9.3 to 0.9‰ and in improving demographic indicators. 

The paper generalizes the 15 years’ experience of the V. A. Negovsky Research Institute of General Reanimatology, Russian Academy of Medical Sciences, in conducting fundamental studies of the morphological, functional, and clinical patterns of the development of acute respiratory distress syndrome (ARDS), by using up-to-date medical technologies. The developed and clinically introduced new scientifically grounded methods for the prevention, diagnosis, and combination, differentiated treatment of ARDS could reduce the number of complications, the duration of mechanical ventilation, the length of stay in the intensive care unit, and mortality rates. Key words: acute respiratory distress syndrome, V. A. Negovsky Research Institute of General Reanimatology, Russian Academy of Medical Sciences.

Objective: to analyze the research areas determining the pathogenesis and correction of critical conditions in obstetric care in the past 15 years on the basis of the dissertations made at the V. A. Negovsky Research Institute of General Reanimatology. Subjects and methods. Nine hundred and twenty-nine pregnant women, parturients, and puerperas were examined; the latter were allocated to comparison groups in terms of age, weight, comorbidity, performed intensive therapy and underwent both retrospective and prospective analysis from 1981 to 2010. The comparison group comprised 44 nonobstetric patients while examining multiple organ dysfunction (MOD) in the purperas. The latter with massive blood loss were separately identified when evaluating the impaired oxygen status in patients with systemic inflammatory response syndrome and MOD. According to the pathology and indicators under study, the puerperas with MOD were examined in a few steps (2 to 7). Water sectoral disorders were detected in three steps: on days 1, 3, and 5; these were identified in four steps in case of eclamptic coma (EC), regional anesthesia, and impaired oxygen status. Results. The findings are suggestive of significant impairments in central hemodynamics (CHD) in the severe forms of gestosis, which are caused by reductions in cardiac index and circulating blood volume, the basis for these is hypovolemia. Dyshidrosis appears as an increased extracellular sector mainly due to interstitial hyperhydration. The low values of arterial blood oxygen, its delivery and uptake, oxygen extract coefficient and the high value of oxygen debt (OD) confirmed blood shunting or circulatory centralization, which was indicative of visceral hypoxia. Determination of the level of cerebral blood flow (CBF) in puerperas with coma showed its diminution due to reduced blood flow in the cortical structures. Regional anesthesia in complicated pregnancy and delivery stabilized CHD, dropped the level of proteinuria, and failed to have a negative impact on the fetus and to cause extragenital manifestations. Conclusion. The proposed algorithms for treating critical conditions in obstetric care contributed to the normalization of CHD parameters, the recovery of water sectoral balance and immune status, resulted in lower mortality rates in MOD, and could increase CBF and minimize OD, reducing the duration of comatous state in EC and the length of stay in intensive care units. 

Endogenous intoxication as a typical pathological process has been and remains one of the key problems in virtually all fields of medicine and mainly in reanimatology. Accumulation of endogenous toxic substances is an integral component of any critical condition and accompanies severe injury, generalized infections, abdominal organ derangement. Loss of the function of detoxifying systems in multiple organ dysfunction leads to progressive endotoxicosis and worsening gas exchange disorders, including detoxification in the organs themselves, thus closing the vicious circle of tanatogenesis. Endogenous intoxication is a multidisciplinary problem that is the area of many different fields of practical medicine, experimental pathophysiology, and biomedical technology. Thus, current efferent therapeutic techniques for critical conditions and extracorporeal detoxification in particular are being introduced into clinical practice. The V. A. Negovsky Research Institute of General Reanimatology, Russian Academy of Medical Sciences, has been studying the theoretical and applied issues concerning the problem of endotoxicosis for many years. This review attempts to generalize the main results the Institute’s activity in this area. Key words: endogenous intoxication, efferent therapy, detoxification.

The paper gives the results of a number of Russian studies in the past 10 years on the pathogenesis of severe concomitant injury accompanied by shock and blood loss and development of its new treatment options. In particular, it considers new experimental and clinical data on changes in hormonal status, lipid metabolism, hemorheology, microcirculation, oxidant-antioxidant balance, neuroimmune endocrine system, and oxygen transport. At the same time the respective pathogenetic principles in the treatment of patients and victims are justified, with special emphasis on the use of antihypoxants and prospects for efferent therapeutic techniques. There are also papers on the pathogenesis and correction of hypoxia in individual categories of trauma patients, those with blunt chest injury and mine blast victims in particular. 

The paper postulates whether the phenomenon of integration of metabolism in man and his microbiome exists. The author’s previously hypothesized fact that small molecules from microbes are involved in human homeostasis [1, 2] has found confirmation in subsequent experimental and clinical studies. The interactions of bacterial metabolites with the human body, which are natural and harmonious in health, are shown to become distorted in different diseases, which may be present in critical conditions at the most and the worsening disintegration results in multiple organ dysfunction and a fatal outcome. Thus, the performed investigations have established that there is a relationship between the severity and outcome of disease and the metabolic profile of low-molecular-weight aromatic compounds from microbes in the patient’s blood and that there are key molecules that are involved in the integrative interaction with human cells among the exometabolites of aerobic and anaerobic bacteria (the main representatives of the human microbiota); the mechanisms of this interaction at the cellular and subcellular levels have been studied. In the author’s opinion, a study of integration mechanisms and the role of microbial aromatic metabolites (MAM) and a search for MAM-oriented therapeutic methods open up new avenues to improve the results of patient treatment in different fields of medicine and mainly in reanimatology. Key words: critical conditions, metabolism, microbial aromatic metabolites, phenylcarboxylic acids, sepsis, intestinal microbiome.

The topic of anesthesia is constantly touched upon in the treatises of the V. A. Negovsky Research Institute of General Reanimatology, Russian Academy of Medical Sciences. The Institute's researchers have studied and perfected general and regional anesthesia, intraoperative protection modes during ambulatory surgical interventions. In 2010, a perioperative critical care laboratory was set up for further investigations of the issues and problems of anesthesiology. The laboratory's main scientific areas are to investigate the negative effects of mechanical ventilation during general anesthesia and ways of their overcome; to study the mechanisms of hypoxic preconditioning, and to attempt to put the discovered phenomenon into clinical practice. Progress and prospects in the selected areas are discussed 

The review considers the pathogenesis of terminal and postresuscitation conditions associated with the pathoneurophysi-ological mechanisms of postresuscitation encephalopathies, the body’s reaction to extreme exposures in relation to individual and typological features, and sex differences. It gives new evidence for the impact of ischemia on the water structure, red blood cell membrane, and cell genome. There is an experimental rationale for the treatment of postresuscitation disease in the context of the systemic synthesis and integration of the body, which ensures the latter’s active participation in its own recovery. Key words: terminal and postresuscitation states, encephalopathy.

The paper analyzes the results of the investigations made at the V. A. Negovsky Research Institute of General Reanimatology, Russian Academy of Medical Sciences, on the pathophysiology and applied aspects of cardiac performance and the anesthetic maintenance of cardiac operations. The main tasks presented to its investigators were to improve electric cardiac defibrillation and cardioversion, to elaborate the optimal infusiotransfusion therapy tactics during cardiac surgery, to optimize intraoperative myocardial protection, to maintain lung functions under extracorporeal circulation, to search for the most effective and safe schemes of general and epidural anesthesia in cardiosurgical patients, and to substantiate algorithms for their postoperative activation. The findings could solve the problem of treating circulatory disorders in the practice of critical care medicine on a new plane. At the same time new areas of a further scientific search have been identified. 

The paper presents the results of a comprehensive study of postresuscitation brain changes at the level of neuronal populations. The study has revealed the general patterns and individual, typological, and sex features of changes in the neuronal populations and determined the association of neurological recovery with morphological changes of these populations. The factors influencing the resistance of neurons to ischemia/reperfusion have been found. The postresuscitation brain changes at the level of neuronal populations have been shown to be of concern in the pathogenesis of posthypoxic encephalopathies. Key words: postresuscitation period; neuronal populations; general patterns of neuronal morphological changes; individual, typological, and sex features.

The paper deals with the problem of anesthetic maintenance during surgical correction of coronary blood flow. The basis for this is the results of the investigations conducted at the V. A. Negovsky Research Institute of General Reanimatology, the objective of which was to improve the results of surgical treatment in patients with different forms of coronary heart disease (CHD), by optimizing the anesthetic maintenance of open heart surgery. Clinical and special examinations were made in 367 patients who had undergone surgical treatment (aortocoronary bypass surgery; formation of a mammary coronary anastomosis; resection and plastic repair of left ventricular aneurysms; thrombectomy from the heart chambers) for CHD and its complications. The main methodological approach to this study is to personalize intensive therapy and general anesthesia, which are relied on both evidence-based medicine and an individual pathophysiological approach. The paper details how to choose the basic mode of general anesthesia depending on the form of CHD and myocardial contractile function. Furthermore, the authors propose methods for optimizing the perioperative period: postoperative analgesia; correction of the aggregate state of blood; operative hemodilution; prevention and correction of critically reduced blood oxygen capacity 

The paper provides the results of the 1990—2010 experimental and clinical studies on the optimization of the efficiency of electrical ventricular defibrillation using the Russian bipolar quasi-sinusoidal impulse. The comprehensive study of the influence of major cardiac and extracardiac factors, such as heart failure, the type and duration of fibrillation, its amplitude and frequency characteristics, chest resistance, electrode sizes, administration of antiarrhythmic drugs, and phase 2 impulse amplitude on the efficiency and safety of defibrillation, could formulate a number of new propositions and solve some methodological and methodic issues. The dose-dependent effectiveness of the quasi-sinusoidal impulse has been first investigated in patients with induced, spontaneous primary and secondary fibrillation and ventricular tachycardia. Low-energy (Key words: defibrillation, bipolar quasi-sinusoidal impulse.

Objective: to study the time course of changes in brain natriuretic peptide (BNP) levels in patients with coronary heart disease, who undergo myocardial revascularization under extracorporeal circulation and to assess a relationship of the level of the biomarker to the clinical data in the early postoperative period. Subjects and methods. Fifty-two patients aged 62.2±1.1 years with a left ventricular ejection fraction (LVEF) of 51.1±1.4% were examined. The concentration of BNP was determined by immunofluorescence assay (Triage Meter Plus, Biosite Diagnostics, USA) before (BNP1) and at the end (BNP2) of surgery, in the morning of the first (BNP3) and second (BNP4) postoperative days. Central hemodynamics was invasively monitored using Swan-Ganz-type catheters. Results. The values of the biomarker were normal (51.6±3.5 pg/ml) in most cases. In the other patients, the level of the peptide was increased up to 165.8±16.1 pg/ml. The relationship between preoperative LVEF and BNP1 was moderate (r=-0.54; p<0.0001). BNP2 correlated closely with BNP1 (r=0.88; p<0.0001). Analysis of the clinical characteristics of the early postoperative period showed that BNP1 had a marked impact on cardiac index (CI) (r=-0.55; p=0.002) and dopamine dosage at the end of surgery (r=0.4; p=0.002), as well as on CI on postoperative day 1 (r=-0.5; p=0.008). In addition, BNP1 significantly affected the length of stay in an intensive care unit (ICU) (r=0.3; p=0.03). BNP2 was related to CI values (r=-0.4; p=0.03) and dopamine dosage (r=0.47; p=0.0004) at the end of surgery. Thus, BNP1 and BNP2, which were closely related, influenced the majority of the clinical characteristics under study. However, only did BNP1 affect the integral indicator «length of ICU stay». BNP3 and BNP4 were closely related and had no significant relationship to BNP1 and BNP2 or impact on the clinical parameters characterizing the postoperative period. Conclusion. The preoperative level of the peptide is related to the characteristics of cardiac performance and the postoperative length of ICU stay. The early postoperative values of BNP are correlated with CI and dopamine dosage both at the end of surgery and on postoperative day 1. The maximum BNP1 values exceeding the baseline ones by more than 4 times are recorded 18—22 hours postsurgery. Then the level of the peptide begins to drop. The clinical and pathophysiological significance of postoperative BNP changes calls for further investigations.