[CORRELATIONS BETWEEN EEG AND RHEOGRAPHIC INDICES OF CEREBRAL BLOOD FLOW IN CHILDREN ON NORTH-EAST OF RUSSIA].

The purpose of the work was an estimation of correlations between EEG spectral parameters and rheoencephalogram (REG) indicators of cerebral blood flow (CBF) in the group of children of 7-18 years old living in the North-East of Russia. Well-known data were confirmed about age-dependent EEG and REG-CBF indicators dynamics. It was not revealed strong coordination between EEG and REG age-dependent changes in this period of life. This may to our opinion speak of relative independence of development of those systems which reflect itself in EEG and REG--structural functional organization of the brain and cerebral metabolic rate. In a narrow age band 14.8-15.6 years old it was found highly significant positive correlation between EEG theta activity and REG amplitude-frequency parameter--indicating CBF. The hypothesis was suggested explaining this fact from the point of view of the down-regulation mechanism of the brain in the period of energy expensive synthetic processes in puberty period.

[Reflection of reserves of the brain energy mechanisms in cerebral blood flow dynamics in human under acute hypoxia].

Results of experimental researches of the cerebral blood flow (CBF) dynamics in human under acute hypoxia have been analyzed in the paper. It was found that changes of CBF under severe acute hypoxia are of nonlinear character and have several phases--the primary growth in the first minutes of hypoxia, relative stabilization and secondary growth. Secondary growth has no relation to changes of the hypoxemia level. It begins earlier under more severe hypoxia and in individuals with less resistance to oxygen deficit. Opposite to this, hypoxic training prolongs the time from the onset of hypoxia till the moment of the CBF secondary growth. The hypothesis was suggested that the CBF secondary growth reflects a phase of certain exhaustion of the brain's neuronal mitochondrial reserve capacity, which is accompanied by accumulation of vasoactive substances--precursors of ATP.

[Effects of acute normobaric hypoxia on free plasma amino acids metabolism in humans].

We demonstrated significant changes in levels of several plasma free amino acids--proline, hydroxyproline, glycine, and phenylalanine--in healthy volunteers in response to severe acute normobaric hypoxia (breathing nitrogen-oxygen mixture with 9% of O2). We assume that demonstrated an increase of free proline, hydroxyproline, and glycine in plasma in the 10th minute of hypoxia was caused by increased collagenolysis due to hypoxic activation of matrix metalloproteinases. Significantly increased levels of free phenylalanine in the 10th and 20th minutes of hypoxia were the consequences of autophagy activation. Our results suggest that acute severe normobaric hypoxia has specific effects on plasma free amino acids in healthy humans.

[Nitric oxide metabolites level in human serum in acute normobaric hypoxia].

The influence of acute normobaric hypoxia on NO metabolites level of the blood serum in volunteers at respiration of hypoxic gas mixture containing 8 % of O2 during 25 min was investigated. Health status of participants and the hypoxia intensity were monitored with a complex of indexes: EEC, ECG, blood pressure, oxygen saturation of haemoglobin, cardiac output, gas composition of exhaled air. Cluster analysis (k-means clustering) conducted among volunteers that have successfully passed the test has shown presence of two groups differing in NO metabolites level during experiment. Statistically significant differences on NO metabolites level between groups were observed before hypoxia exposure, on 10th minute of acute hypoxia (maximum difference) and on 5th minute of recovery. Differences on NO metabolites level between groups have been caused by changes in nitrates concentration whereas nitrites level did not differ. The least NO and nitrates levels have been revealed in volunteers that have been in volunteers that had interrupted performance of the test after 10 minutes of respiration of hypoxic gas mixture. Thus the moderate increase of NO metabolites level due to accumulation of nitrates at acute hypoxia testifies to good adaptive reserves of system of nitric oxide generation in organism.

[Individual systemic reactions of human organism under acute hypoxia].

Results of physiological and biochemical study including analysis of brain electrical activity dynamics, volumetric and linear parameters of cerebral blood flow, plasma stress hormones levels (adrenaline, noradrenaline, cortisol) and energy metabolism markers (glucose, lactate) at different stages of acute normobaric hypoxia are presented. The correlations are shown between alterations of main cerebral arteries tone and resistivity type vessels, as well as between changes in linear and volumetric cerebral blood flow providing a compensation of the oxygen deficit. Features of EEG dynamics were investigated that characterized CNS regulatory functions and brain electrogenesis disturbance under deep stages of hypoxia. By means of original evaluating methods of interaction structure between different EEG rhythm, EEG markers were obtained that revealed both brain intercentral interaction rearrangements and functional disintegration of systemic brain activity at various stages of acute hypoxia.

[Changes of external respiration, brain circulation and the EEG in acute hypoxia in the subjects with different hypoxic resistance].

Two groups of individuals were distinguished in experiments with acute hypoxic action (respiration of oxygen-nitrogen mixture with 8 % oxygen content) - with low (LHR) and high (HHR) resistance to hypoxia. In subjects of the LR group, slowing down of the pulse rate and lowering of arterial pressure in the shoulder artery were observed on the 5th-10th minute of hypoxia. In the HHR subjects, primary growth of the pulse rate was followed by its stabilization; no significant changes of the arterial pressure were observed. In LHR subjects, in the first 5-10 min of the hypoxia, a significantly lower level of the blood oxygen saturation was observed in comparison to the HHR. In the LHR group, there was a higher increment of amplitude-frequency index of the rheoencephalogram in comparison to the HHR, indicating a higher increment of the cerebral blood flow. The slowing down of the pulse rate in the LHR subjects was accompanied with increasing cerebral pulse volume, so that in spite of the pulse rate slowing, the minute volume of cerebral circulation increased. In the LHR subjects, two-phased dynamics of the EEG was observed: in the first phase there was a slow growth of theta- and delta-band EEG spectral power, in the second phase (on the 5th-10th min of hypoxia), sharp (200-300 % of the background level) growth of the EEG spectral power in those bands was observed. In the HHR subjects, gradual growth of EEG spectral power occurred with relative stabilization on the 10th-12th min of hypoxia. Possible role of the stress in the collapse-like reaction during acute hypoxia is analysed, which might cause increase of the oxygen request of the brain, higher growth of cerebral blood flow and more pronounced lowering of functional activity of the brain in the LHR subjects.

[Serum glucose level in acute severe hypoxia in human at rest].

Study of the effects of acute normobaric hypoxia was performed on a group of young healthy males (age 19-23, n = 10). Conditions of acute normobaric hypoxia were modeled by using oxygen-nitrogen mixture containing 8% of oxygen as a breath gas. That level of oxygen corresponds with its partial pressure at 7000 meters above sea level. A number of different analyses were conducted during experiment: levels of glucose, pyruvate, lactate in peripheral venous blood, hemoglobin, pH, hematocrit, partial pressures of 02 and CO2, hemoglobin saturation. It was shown that on 5th minute of hypoxia serum glucose level decreased significantly (p < 0.05). The average decrease was about 0.76 mmol/l in its maximum and lowest individual glucose levels were 4.0 mmol/l or higher. Serum glucose level returned to background values (assessed before the test) at 10th minute of experiment. In our opinion results of the study suggest that syncopal form of height hypoxia may be caused by the reasons other than hypoglycemia.

[Fatty acid of human plasma under the influence of acute strong normobaric hypoxia].

The influence of acute normobaric hypoxia on total pool of human plasma fatty acids was studied in experiment (respiration of hypoxic gas mixture containing 8% of O2, during 25 min). Health status of participants-volunteers and the hypoxia intensity were monitored with a complex of electrophysiological methods: EEC, ECG, measurement of blood pressure, SpO2, evaluation of cardiac output, gas analysis of exhaled air. Using gas chromatography we studied plasma fatty acids total profile (esterificated and non-esterificated) before hypoxia exposure, on 2nd, 5th, 10th, 20th minutes of acute hypoxia and on 5th and 15th minutes of recovery. It was shown that blood saturation value dropped to 52.1 +/- 7.1 % on 25th minute of hypoxia exposure. There were no statistically significant changes in concentrations of total fatty acids, saturated fatty acids, monounsaturated palmitoleic acid, polyunsaturated linoleic and linolenic acids. Significant (p < 0.05) decrease of concentration of oleic and arachidonic acids was displayed that persisted after 15 minutes of recovery period. It is possible to assume that these changes in unsaturated fatty acid concentration were caused by activation of free radical oxidation processes and production of oleic acid derivatives. The performed hypoxic test seemed to be sufficient in order to reveal hypoxia effects on metabolism of individual unsaturated fatty acids.

Cortical-subcortical interactions and the regulation of the functional state of the brain in acute hypoxia in humans.

The mechanisms regulating the functional state (FS) of the brain were studied in humans in conditions of dosed acute hypoxia (breathing a mixture of 8% oxygen in nitrogen for 15-25 min). The dynamics of the FS of the brain due to changes in the balance of the activities of brain regulatory structures in hypoxia were reflected in rearrangements of EEG spatial relationships (factor and cluster analysis of EEG crosscorrelation matrixes) and the redistribution of intracerebral locations of electrically equivalent dipole sources (EEDS), with increases in EEDS density in the projections of the medial and basal parts of the temporal lobes of the hemispheres (EEDS tomography data). Changes in cortical-subcortical interactions were characterized by a decrease in the tone of the activatory brain system, a decrease in the inhibitory control of subcortical structures by neocortical formations, and activation of limbic system and hypothalamic structures. Switching of the integrative regulatory mechanisms from the cortico-thalamic level to the limbic-diencephalic level may allow release of the energy-consuming nonspecific components of hypoxic stress and more stable regulation of physiological parameters by the major vital systems in conditions of increasing oxygen deficit.

Interaction of hypocapnia, hypoxia, brain blood flow, and brain electrical activity in voluntary hyperventilation in humans.

Changes in various physiological measures in voluntary hyperventilation lasting three minutes or more in humans were studied and compared. Three-minute hyperventilation, in which the rate of external ventilation increased by an average factor of 4.5-5, produced similar phasic changes in central and brain hemodynamics. The rate of circulation, indicated by rheographic data, initially increased during hyperventilation, reaching a maximum at 1-2 min of the test; there was then a reduction, to a minimum 2-3 min after the end of the test; this was followed by a further slow increase. The rate of cerebral blood flow during all 3 min of hyperventilation remained elevated in most subjects as compared with baseline and decreased during the 5 min following the end of the test. Transcutaneous carbon dioxide tension changed differently - there was a decrease to a minimum (about 25 mmHg) by the end of the test, lasting 1 min from the end of the test, this being followed by an increase to a level of 90% of baseline at 5 min after the test. Blood oxygen saturation remained at 98-100% during the test, decreasing to about 90% 5 min after the test; this, along with the decrease in cerebral blood flow, was a factor producing brain hypoxia. In different subjects, changes in the spectral power of oscillations in different EEG ranges on hyperventilation were "mirrored" to different extents by the dynamics of transcutaneous carbon dioxide tension. The duration and repetition of hyperventilation were important factors for understanding the interaction between brain hemodynamics, hypocapnia, hypoxia, and brain electrical activity. After several repetitions of 3-min hyperventilation over a period of 1 h, the increasing brain blood flow could decrease significantly on the background of relatively small changes in brain electrical activity. The data presented here were assessed from the point of view of the important role of brain tissue oxygen utilization mechanisms in adaptation to hypoxia and hypocapnia.

[Cortical-subcortical interactions and the brain functional state regulation under acute hypoxia in man].

Regulation mechanisms of the brain functional state (FS) were studied in man during acute hypoxic conditions (inhalation of 8% O2 hypoxic air for 15-25 minutes). Changes in balance of the brain regulatory structures activities caused by hypoxia determine FS dynamics that is reflected in the reorganization of the EEG spatial interrelations (by data of factor and cluster analysis of EEG cross-correlation matrices), as well as translocation of intracerebral position of electrical equivalent dipole sources (EEDS) coupled with EEDS density rising in medial and basal regions of the cerebral hemisphere temporal lobes (by EEDS-tomography data). Alterations of the cortical-sub-cortical interactions show a decline in the brain activating system tone, a decrease in the neocortical inhibitory control of subcortical processes, and activation of structures of limbic and hypothalamic regions. Switching of integrative regulatory control mechanism from "cortical-thalamic" system level to "limbic-dyencephalic" one could ensure both removal of powerful unspecific components of hypoxic stress and a greater stability of essential physiological parameters of the main vital functions regulation during oxygen deficiency accumulation.

[Interrelations of hypocapnia, hypoxia, cerebral blood flow and electrical activity of the brain under voluntary hyperventilation in humans].

Changes of different physiological parameters in human caused by hyperventilation of 3-min and longer duration were investigated and correlated. It was found that during 3-min hyperventilation, resulting in 4.5-5 fold increase of the respiration velocity, similar phasing changes of the central and cerebral haemodynamics occurred. The blood flow velocity according to the rheographic data during the hyperventilation first increases, reaching maximum at 1st - 2nd min of the test, and then decreases, reaching minimum at 2nd - 3rd min after it's end, and then slowly increases. Cerebral blood flow velocity during all the 3 min of the hyperventilation in most of the subjects keeps being increased, and after the test - decreased. At the same time transcutaneous pressure of carbon dioxide changes differently - decreases to minimum (approximately 25 mmHg) at the end of the test and then increases, reaching approximately 90% of the background level, at 5th min after the end of the test. Oxygen saturation of the blood during the test is found to be 98-100% and decreases to 90% at 5th min after it's end, which in overall with cerebral blood flow decrease appears to be the factor of the brain's hypoxia. In different subjects "mirror" changes of the EEG spectral power of different EEG ranges in relation to transcutaneous pressure of carbon dioxide dynamics were revealed by the hyperventilation. Taking into account the factors of duration or recurrence of the hyperventilation is important for the understanding the interrelations of cerebral haemodynamics, hypocapnia, hypoxia and electrical activity of the brain. It was found that after the recurrent hyperventilation of increasing amount (several times in hour by 3 min) cerebral blood flow might decrease markedly against the background of relatively small changes of electrical activity of the brain. The discussing of the data presented in the paper is carried out from the point of view of important role of tissue oxygen utilization mechanisms of the brain in adaptation to hypoxia and hypocapnia.

Characteristics of the formation of systems activity in the brain and autonomic functions in children in conditions of the European North (discussion paper).

Results obtained from complex medical-physiological investigations performed during 10 scientific expeditions in the Arkhangel'sk Region in 2003-2005 are presented. The effects of climatological-geographic, biogeochemical, and social conditions of the conditions obtaining in the Far North region of Russia on sexual maturation, formation of the structural-functional organization of the brain, autonomic functions, and immunological and biochemical status of schoolchildren were studied using state-of-the-art neurophysiological methods (computerized electroencephalography, computerized rheoencephalography, computerized electric dipole origin tomography, etc.), psychophysiological and psychometric methods (assessment of the state of cognitive and memory functions, Wechsler intellectual scale), along with biochemical assay of monoamine oxidase (MAO, the key enzyme in adrenergic neurotransmitter metabolism) and the liver enzyme butyrylcholinesterase (BuChE) and physicochemical analysis of the levels of macroelements and trace elements in the body.

Interaction between changes in local and temporospatial spectral EEG characteristics during exposure of humans to hypoxia.

The temporospatial and local characteristics of the EEG were studied in healthy subjects during the respiration of a hypoxic oxygen-nitrogen gas mixture containing 8% oxygen. Analysis of the spectral power density, coherence, phase shift, similarity of dominant frequencies in the EEG in different leads was performed separately for epochs containing and not containing visually apparent patterns of EEG spatial synchronization. In addition, assessment of spectral measures took account of the fact of the dominance of the frequency being analyzed in the EEG spectrum of the corresponding lead. The results of these studies showed that overall, hypoxia was accompanied by a decrease in EEG coherence in the alpha range and, for connections in the left mid-temporal lead, the delta range. The beta range showed an increase in the values of this measure, while the theta range showed different changes in coherence: increases in epochs containing spatial synchronization patterns and decreases from control levels in other epochs. Hypoxia was also associated with increases in the EEG phase shift in the frontal and temporal leads (in relation to the EEG recordings in the other leads) in the delta and theta ranges. In the beta range, conversely, there was a decrease in the mean phase shift. Consideration of the fact of dominance of one or another frequency in the spectra of local EEG traces is needed for correct interpretation of analyses of temporospatial measures. A mathematical model of the interaction between processes at different frequencies is presented to explain some of the observations in the current work.

[Individual specifics of oxygen consumption by the human organism in hypoxia].

Influence of hypoxia on a human organism was studied with the help of hypoxic gas mixtures (HGM) in the first series with 14 % content of oxygen in nitrogen (n = 6), in the second one--with 12 % (n = 10) in the third one--with 8 % (n = 14). Hypoxic exposition in all the series was 25 min. In 6 subjects engaged in all the 3 series, physical working capacity was assessed in two-step test on a veloergometer. In all the 3 series, oxygen consumption by the organism some time after the start of the hypoxic action exceeded the background normnoxic level. Maximal value of this excess on the average was the highest in HGM-12 series--40 +/- 12 %. Maximal increase of the respiration and central blood circulation velocity was the highest in HGM-8 series, 90 +/- 24 and 25 +/- 16 % respectively. Analysis of the EEG parameters, oxygen saturation and rheoencephalographic data indicates the probability of the cerebral metabolic rate of oxygen during hypoxia to beein normal (in most subjects) and even increased (in some subjects). In 3 subjects of 6, whose physical working capacity was assessed, maximal increase of oxygen consumption was observed in HGM-8 series--105 +/- 34 %. Their physical working capacity was higher than of those subjects, who showed maximal increase of oxygen consumption in HGM-12 series. Analysis of increase in oxygen consumption (paradoxical under hypoxic conditions) doesn't allow to ascribe it wholly to an increase of the respiration and central blood circulation. Obviously, the increase of oxygen and energy expenditures for biochemical adaptation to hypoxia, which has common features with adaptation to physical activity plays an important role under hypoxia.