Objective: to study a number of free-radical reactions, the parameters of cholesterol exchange, and the extent of blood cell DNA damages in victims early after concomitant injury. Subjects and methods. The study covered 77 patients who had experienced severe mechanical injury. The patients’ condition on admission was an APACHE II of 19.1±5.4 scores. According to the outcome of the disease, all the patients were divided into 2 groups: 1) deceased patients and 2) survivors. The study was conducted on admission to an intensive care unit and on days 3, 5, 7, and 15. The extent of blood cell DNA damages and the proportion of apoptotic and necrotic blood cells were estimated by gel isolated cell elec-trophoresis (DNA rocket electrophoresis). The «Human 8-oxoGuanine DNA Glycosylate (OGG1) FLARE Assay» kit was used to measure the content of 8-hydroxy-2-deoxyguanosine in cell DNA. The cholesterol and overall antioxida-tive statuses and biochemical parameters were determined on an automatic biochemical Cobas Miras Plus analyzer. Very low-density lipoproteins (VLDL) and low-density lipoproteins (LDL) were calculated. Results and discussion. In severe concomitant injury, there were increases in DNA damages in the blood cells and in their apoptotic and necrotic processes, which were particularly pronounced on days 3—5. In the group of deceased patients, the increase of 8-hydroxy-2-deoxyguanosine was greater than the normal values on days 5 and 7. On admission, the systemic antioxidative status was greater than the normal values in the survivors and deceased patients and tended to diminish in both groups during an observation. The average statistical values of total cholesterol were lower at all stages of the study. At the stages of the study, the concentration of triglycerides and VLDL were in the normal range in all the patients. At week 1 of the observation, the level of LDL was normal or greater in the survivors than in the deceased. The changes in high-density lipoproteins were characterized by their decreased plasma levels throughout the observation of the victims. In both groups, the activity of alkaline phosphatase increased over time and was 1.5—2 times higher than the normal values on days 15. In the survivors, the admission activity of y-glutamyltransferase (y-GT) was in the normal range. The activity of the enzyme in this group tended to increase, so did the plasma level of total protein in these patients. Conclusion. In severe concomitant injury, there is an increase in DNA damage processes, which is associated with the enhanced cell death. The time course of changes in the levels of total cholesterol, LDL cholesterol, and total protein and in the activities of y-GT and 8-hydroxy-2-deoxyguanosine may be used as predictors. Key words: apoptosis, necrosis, DNA damage, 8-hydroxy-2-deoxyguanosine, cholesterol exchange, injury.

Objective: to study the efficiency of pre-administration of hypoxen in experimental cardiac contusion in order to lower the degree of posttraumatic myocardial dysfunction. Materials and methods: experiments were carried out on non-inbred albino male rats anesthetized with sodium thiopental. Cardiac contusion was reproduced by an original device that imitated a blow of the steering wheel to the anterior chest, as that observed when a moving car clashes against an obstacle. Some animals were traumatized after pre-administration of hypoxen. An electrocardiogram, left carotid blood pressure (BP), an integral rheogram, and the first derivative of a differential rheogram were recorded prior to cardiac contusion simulation and in different posttraumatic periods. Stroke volume (SV), cardiac output (CO), and total peripheral vascular resistance were calculated. Results. Preinjection of hypoxen completely prevented the development of sinus arrhythmia, paroxysmal ventricular tachycardia, and intraatrial and intraventricular conduction disturbances, irrespective of the baseline BP. In a subgroup of animals with a baseline low BP, the agent reduced the incidence of bradycardia by 1.5 times, heterotopic rhythms by 5.3 times, ventricular premature contractions by 6 times, atrioventricular (AV) block by 5.3 times and diminished the changes in the terminal of a ventricular complex by 6.3 times. In a subgroup of animals with baseline normal BP, bradycardia and heterotopic rhythms were recorded 2 and 7 times more infrequently recorded; ventricular premature beats, AV block, and ST-segment displacement were present in none case. Preinjection of hypoxen improved myocardial contractility, as evidenced by 17—25% SV increases within an hour posttraumatically. However, significant arterial hypotension and lowered CO due to bradycardia in most experimental animals during the preinjection of hypoxen before injury and throughout the posttraumatic period caused a ten-fold increase in mortality rates as compared with the non-hypoxen group. Conclusion. The hemodynamic effects of hypoxen can substantially limit the possibility of using the agent to diminish the degree of posttraumatic cardiac dysfunction. Key words: experimental cardiac contusion, central hemodynamics, hypoxen.

Objective: to evaluate the possibilities of using transcranial Doppler study in pregnant women and pueperas with preeclamp-sia. Subjects and methods. Two hundred and thirty-two pregnant women diagnosed as having varying preeclampsia were prospectively studied. A comparison group comprised 90 apparently healthy women in the third trimester of pregnancy. All the respondents underwent transcranial duplex scanning of the medial cerebral artery with the linear velocity values being determined. A number of the values reflecting the level of perfusion and intracranial pressures, hydrodynamic resistance in the system, cerebrovascular responsiveness and the state of the vascular wall were calculated. Correlation analysis was made between the parameters of cerebral circulation and the severity of preeclampsia, proteinuria, the severity of hydrops, and the parameters of central and peripheral hemodynamics. Results. The findings suggest that there is impaired cerebral perfusion in pregnant women and puerperas with varying preeclampsia, the severity of cerebral circulatory disorders being in proportion with that of preeclampsia. There is a close correlation between cerebral circulation and the individual criteria determining the severity of preeclampsia. The linear values of the Doppler spectrum, namely linear flow characteristics, are prognos-tically most significant. Conclusion. The introduction of transcranial Doppler study into obstetric care has permitted the authors not only to study cerebral circulatory disorders in healthy and pregnant women and puerperas with preeclampia in detail, but also to establish a number of highly significant prognostic criteria for the severity of this life-threatening complication of gestation. The results of transcranial Doppler study assist practitioners in timely and accurately solving the problems in the diagnosis of preeclampsia and in evaluating its severity. Cerebral circulatory values may be successfully used to ascertain the efficiency of therapeutic interventions and the expediency of pregnancy prolongation. Key words: transcranial Doppler study, preeclampsia, eclampsia, cerebral circulation, severity criteria, prediction.

Objective: to determine the nature and specific features of development of endogenous intoxication in pregnant women with arterial hypertension. Subjects and materials. Humoral extracellular fluid volume regulation, partial renal functions, placental hormonal function, membranous lipid peroxidation activity, antiradical defense, the parameters of central hemodynamics, endogenous intoxication, and a biochemical coagulogram were studied and differential blood count with the leukocytic ratio indices was estimated in 172 pregnant females with arterial hypertension and 54 healthy pregnant ones in the third trimester. The statistical package «Stadia» was applied. Results. Arterial hypertension caused by pregnancy was ascertained to involve pathogenetically different types: low-, normal-, and high-renin ones. In pregnant women with arterial hypertension, the general pathogenetic homeostatic changes were placental hormonal imbalance, activated membranous lipid peroxidation, impaired lymph outflow, sodium and water retention, hepatic and renal failure, and endogenous intoxication. Conclusion. Placental ischemia appearing as placental hormonal imbalance (extrarenal pressor system) was accompanied by a compensatory humoral response: arterial hypertension and metabolic disturbances. Changes in medium-weight molecule 280, leukocytic intoxication index, erythrocytic sorption capacity, and Paramecium test, by confirming the presence of endogenous intoxication in pregnant females with arterial hypertension, were caused by a type of arterial hypertension (by the hemodynamic profile and the type of impaired partial renal functions). Key words: pregnancy, arterial hypertension, endogenous intoxication.

Objective: to establish the common regularities and etiological features of lipid metabolic changes in critical conditions of various etiology. Subjects and materials: 102 patients with sepsis, severe mechanical injury, and moderate gestosis were examined. The patients were divided into groups according to the etiology and severity of a condition. The patients’ age was also kept in mind in severe mechanical injury. The plasma concentrations of triglycerides (TG), total cholesterol, high-density lipoprotein cholesterol (HDLC), low-density lipoprotein cholesterol (LDLC), and very low-density lipoprotein cholesterol (VLDLC) were determined. Results. There were atherogenic changes in lipid metabolism, which were characterized by a rise in the level of TG and accordingly VLDLC with decreased HDLC concentrations. In sepsis and gestosis, the changes in TG and VLDLC levels occurred in the range of the concentrations exceeding the physiological normal values. In sepsis, the positive changes in these parameters were associated with a good clinical outcome. In mechanical injury, the increase in TG and VLDLC levels occurred in the physiological normal range and it was more significant in fatal outcome. Conclusion. Atherogenic changes in lipid metabolism are a common regularity in critical conditions, they are characterized by an increase in TG and VLDLC levels with decreased HDLC concentrations, show various trends, and occur in different ranges of concentrations depending on the etiology and severity of a condition. Key words: dyslipidemia, atherogenesis, critical conditions, severe mechanical injury, gestosis, sepsis.

Objective: to determine the mechanisms responsible for impairments in the space-time organization of erythropoiesis (SPOE) in experimental sepsis. Materials and methods. The diurnal changes in the titer of erythropoietin, the content of red blood cells, and their distribution by volume, the peripheral blood levels of hemoglobin and reticulocytes, life span, the production of erythrocytes, malonic dialdehyde (MDA), the statokinetic erythroid cell index, and bone marrow 59Fe incorporation were studied in 240 Wistar rats with multimicroial sepsis and 80 intact animals. Results. In sepsis, SPOE desynchronism was found to be due to increases in MDA and in the population of microcytes with shorter life span. The maximum duration was increased for erythropoiesis and decreased for erythrocytic production with the decreased peripheral blood level of ery-throcytes and hemoglobin. The progressive rise in the titer of erythropoiesis was accompanied by decreases in the statoki-netic index and bone marrow 59Fe incorporation with a simultaneous increase in the population of microcytes and with a reduction in the life span of erythrocytes. Conclusion. Endotoxicosis was established to play the leading role in the mechanisms of SPOE desynchronism. Activation of lipid peroxidation in the red blood cell membranes enhances their rigidity, by initiating the development of anemia and microcirculatory disorders. The decreases in erythrocytic production, statokinetic index, and bone marrow 59Fe incorporation with an inadequately high titer of erythropoiesis suggest the inhibition of ery-thropoietin-dependent processes in the target cells, which promotes the progression of septic anemia. Key words: bio-rhythms, erythropoiesis, erythropoietin, anemia, sepsis.

Objective: to reduce the incidence of postoperative complications after high-risk abdominal surgery. Subjects and methods. The study enrolled 69 patients undergoing operations on the upper abdomen. The patients were randomized into 2 groups: 1) those who received total intravenous anesthesia with prolonged thoracic epidural anesthesia (a study group); 2) those who had total intravenous anesthesia with postoperative analgesia with promedol and ketorolac (a control group). The course of anesthesia and the period of early postanasthesia adaptation, the quality of postoperative analgesia and the parameters of external respiratory function, acid-base balance, and gas composition in the arterial blood were studied; the pattern of postoperative complications was also analyzed. Results. Epidural anesthesia considerably reduced the consumption of narcotic analgesics and myorelaxants at surgery, which was followed by the accelerated early postanesthesia adaptation of patients. Postoperative analgesia adequacy was much higher in the study group patients. Postoperatively, there were significant external respiratory dysfunctions of the restrictive type in both groups; however, they were much less pronounced in the study group. In the postoperative period, the control patients were observed to have significant and persistent hypoxemia, presumably associated with the development of microatelectases. There was a reduction in the incidence of respiratory and surgical complications in the study group. Conclusion. Prolonged epidural anesthesia versus anesthesia with narcotic analgesics used during high-risk abdominal surgery accelerates early postanesthesia adaptation and ensures a more adequate postoperative analgesia, resulting in a reduction in the severity of external respiratory dysfunction and impaired blood gas composition, by leading to a decrease in the incidence of postoperative complications. Key words: epidural anesthesia, surgery, external respiratory function, hypoxemia, complications.

The authors consider V. A. Negovsky's philosophical views of the processes of human dying and reanimation, which are presented in his philosophical articles. Particular emphasis is laid to the definition of death, the separation of the concepts of clinical and biological deaths, to the introduction of the concept of social death and the problem «life after death».

10th Anniversary Symposium «Sepsis 2007», Paris, September 27—29, 2007 

Objective: to study the specific features of purine metabolism in clinically significant acute cerebral ischemia. Subjects and materials. Three hundred and fifty patients with the acutest cerebral ischemic stroke were examined. The parameters of gas and electrolyte composition, acid-base balance, the levels of malonic dialdehyde, adenine, guanine, hypox-anthine, xanthine, and uric acid, and the activity of xanthine oxidase were determined in arterial and venous bloods and spinal fluid. Results. In ischemic stroke, hyperuricemia reflects the severity of cerebral metabolic disturbances, hemodynamic instability, hypercoagulation susceptiility, and the extent of neurological deficit. In ischemic stroke, hyperuri-corachia is accompanied by the higher spinal fluid levels of adenine, guanine, hypoxanthine, and xanthine and it is an indirect indicator of respiratory disorders of central genesis, systemic acidosis, hypercoagulation susceptibility, free radical oxidation activation, the intensity of a stressor response to cerebral ischemia, cerebral metabolic disturbances, the depth of reduced consciousness, and the severity of neurological deficit. Conclusion. The high venous blood activity of xanthine oxidase in ischemic stroke is associated with the better neurological parameters in all follow-up periods, the better early functional outcome, and lower mortality rates. Key words: hyperuricemia, stroke, xanthine oxidase, uric acid, cerebral ischemia.

The paper descries a specific view on the mechanism responsible for development of the resistance of an inflammatory process in the female genital tract to drugs and on the role of a free radical process activation factor in the pathogenesis of the disease. Emphasis is laid on the importance of measures to diminish cell membrane permeability, by correcting their structural and functional states with antioxidants. Key words: inflammatory processes in the female genital organs, lipid peroxidation, antioxidative defense, cell membrane structural and functional state.

Objective: to study the plasma levels of steroid hormones and the rates of neurological recovery in the early postresuscitative period after 10-min cardiac arrest in albino male and female rats in the control group and in the study group receiving estradiol + dehy-droepiandrosterone. Materials and methods. Forty-eight animals of both sexes that had experienced under ether anesthesia a 10-min cardiac arrest due to intrathoracic ligation of its vascular fascicle were examined. After standard cardiopulmonary resuscitation, placebo was intramuscularly injected in 31 animals and 17 animals received estradiol and dehydroepiandrosterone in a dose of 0.1 mg and 5 mg per 100 g of ginodian depot (Shering, Germany) used for prolonged correction of the postcastration syndrome in women. Then the general and neurological statuses were evaluated in the animals. Enzyme immunoassay was used to determine the plasma concentration of 7 sex steroids in normalcy (18 intact animals), in the control animals in the untreated animals (n=31) on days 2 and 16 following resuscitation and in the hormone-treated (n=17) animals only on day 16. Results. The processes of dying and cardiovascular resuscitation did not differ significantly in the male and female groups. During the days which followed, there was a more rapid neurological recovery in female rats as compared with male rats in both the control group and the hormonal treatment group with the accelerated external recovery in the latter. There were significant gender differences in the plasma hormonal profile in normalcy and in the postresuscitative period in the controls, which were leveled after treatment. Conclusion. The gender differences in the results of postresuscitative recovery are associated with the specific features of the profile of endogenous reproductive steroids in the organism. Functional recovery following clinical death may be accelerated by exogenous sex steroids. Key words: gender differences, clinical death, reproductive steroids, neurological deficit.

Objective: to study changes in the microcirculatory bed and in the levels of nitric oxide in the rat brain and retina during a long (35-day) postresuscitative period. Materials and methods. A model of clinical death from acute circulatory arrest was used to evaluate the cerebral and retinal microvessels in the rat brain and retinal histological specimens (stained with hematoxylin-eosin and Indian ink) and to record the content of stable end metabolites of nitric oxide (nitric ions) in the study organs, by employing the Griss reaction. Results. The cerebral circulatory changes were characterized by significantly impaired vascular patency, decreased capillary network density, and a lower capillary diameter, which was most pronounced within the first 24 hours after resuscitation. The microcirculatory retinal circulatory disorders featured the staging of the course: vasodilatation and decreased capillary network density within the first 24 hours after resuscitation, followed by a progressive increase in the density of the capillary network from day 14, as compared with the control, and capillary diameter normalization. The study of nitric oxide metabolites in the cerebral cortex and retina of the experimental animals revealed their accumulation increase, that was statistically significantly 1.5 times greater or more than the control values, within 5 postresuscitative weeks. Conclusion. The long (35-day) postresuscitative period exhibited a heterodirectional change in the size and density of the cerebral and retinal microcirculatory network along with a parallel increase in the level of nitric oxide metabolites in the tissues of the rat cerebral cortex and retina. Key words: postresuscitation disease, cerebral microcirculation, ocular microcirculation, nitric ions.

Objective: to study the safety and clinical and economic efficiency of early activation of children operated on under extracorporeal circulation (EC). Subjects and methods. Sixty-eight children aged 4—14 years (8.6±0.4 years) operated on under EC for congenital heart diseases (CHD) were examined. In accordance with the time of switching to spontaneous respiration and tracheal extubation, 2 groups were identified: 1) those who received postoperative artificial ventilation (AV) for 2.9±0.2 hours (a study group); 2) those who had AV for 8.7±0.7 hours (a control group). Both groups did not differ in age, cardiac diseases, their severity, anthropometric characteristics, EC duration, aortic ligation time, and abnormality pattern. In the study group, anesthesia was maintained with fentanyl (5.3±0.1 ^g/kg/hr), diazepam (0.15±0.01 mg/kg/hr), and inhaled ftorotan or enflurane. Diazepam was discontinued in the postperfusion period. The control group received fentanyl (7.6±0.4 ^Bg/kg/hr), diazepam (0.3±0.02 mg/kg/hr), droperidol (0.4±0.04 mg/kg/hr), and/or sodium oxybutyrate (81±5 mg/kg/hr). Myoplegia was provided by pancuronium or pipecuronium that was continuously infused until EC was completed in Group 1 and intermittently injected until the end of surgery in Group 2. Results. There were no indications for tracheal reintubation in both groups of patients. The early postoperative period was uncomplicated in 97.2% of the children in the study group and in 28.1% in the control group (p<0.05). The incidence of pulmonary complications was 2.8 and 46.9%, respectively (p<0.05). In the children from Groups 1 and 2, the duration of a resuscita-tive period was 44.2±1.7 and 77.3±4.9 hours, respectively (p<0.05), and that of the whole postoperative period was 12.6±0.3 and 18.0±1.1 days (p<0.05). In the study group, the total final expenditures, including the cost of anesthesia and treatment for postoperative complications, decreased by 127.5% as compared to the control group (p<0.05). Conclusion. Early activation causes a substantial reduction in the number of pulmonary complications and in the duration of all postoperative treatment stages in children with CHD, which permits the cost of cardiosurgery to be significantly decreased under the conditions of a regional clinical hospital. The procedure of total anesthesia that provides activation within 6 hours may be based on the use of the least expensive drugs (fentanyl, diazepam, ftorotan, pancuronium or pipecuronium). Key words: early activation, artificial ventilation, congenital heart diseases, pulmonary complications, cost effectiveness.

Objective: to evaluate the efficiency of continuous venovenous hemofiltration in patients with generalized peritonitis complicated by multiple organ dysfunction. Subjects and methods. Thirty-seven patients with acute generalized peritonitis were examined. Continuous hemofiltration was used during traditional therapy in Group 1 (n=17); the remaining patients (a control group) received only traditional therapy. The time course of changes in the parameters of toxemia and a hemo-stasiogram were studied. Results. The study indicated better homeostatic parameters, regression of multiple organ dysfunctions, and lower mortality rates in the use of the above procedure. There was a reduction in the count of platelets during hemofiltration, which restored after the end of the procedure. Key words: generalized peritonitis, multiple organ dysfunctions, hemofiltration.

The present views of the pathogenesis of neuronal dysfunction in critical conditions are analyzed, by taking into account of impairments of cellular NAD+ metabolism, the activity of NAD+-converting enzymes, including ADP-ribosyl cyclase/CD38, the possibilities of developing new neuroprotective strategies. Key words: neuronal dysfunction, ADP-rybosyl cyclase/CD38, NAD+, critical condition.