Human Systemic Reactions to a Dosed Exposure to Hypoxia: A Multiparameter Study

Human physiological reactions to acute hypoxic hypoxia were studied. Analysis of simultaneously recorded parameters of various physiological systems showed the following: activation of the general antihypoxic defense system is based on the formation of an intricate structure of intra- and intersystemic relations of specific and nonspecific elements of adaptation that support vital body functions during environmental oxygen deficit. These specific elements become more important in more severe hypoxia, which suppresses metabolism in some organs and tissues because of redistribution of blood flow. These factors allow the body to function at a lower oxygen tension in its tissues owing to an increased efficiency of mitochondria as a result of changes in the kinetics of enzymes of the mitochondrial respiratory chain. In acute hypoxia, the structure of intra- and intersystemic relations is rather intricate; its functional hierarchy is maintained by stronger individual amplitude-related controlling factors and by modulation of their phase- and time-related links. Advanced stages of hypoxia are associated with disintegration of central regulatory mechanisms, which is manifested by disturbances in amplitude-frequency and spatiotemporal parameters of the brain bioelectrical activity, changes in phasic interactions between elements of regulatory mechanisms, and signs of deregulation and decompensation of vital functions. The interpretation of the results is based on the general theory of adaptation, Medvedev's idea of adaptation as a successive involvement of genetically predetermined and newly-formed regulatory programs of the brain, Anokhin's theory of functional systems, and modern concepts of molecular and biochemical mechanisms of hypoxia. It was concluded that artificial normobaric hypoxia is a unique, biologically adequate model that makes it possible to study the rearrangements in systemic and autonomic regulatory mechanisms in response to strictly determined changes in the environmental concentration of oxygen as a principal factor supporting life.     

Changes in the state of the histamine--diamine oxidase and serotonin--monoamine oxidase systems and the activity of the sympatho-adrenal system following experimental occlusion of the aortic trifurcation in dogs

Experiments on 12 dogs have shown that alterations in the intrasystemic parameters of histamine-diamine oxidase, serotonin-monoamine oxidase, adrenaline-noradrenaline and in the intersystemic patterns of adrenaline-histamine indicate the biological adaptation under conditions of embolism of aorta trifurcation induced by 3-hour occlusion. Alterations in the activity of the enzymes studied underlie the adaptational syndrome. During 6-hour occlusions the activity of monoamine oxidase was relatively decreased. Meanwhile the content of serotonin and noradrenaline remained at a high level. These amines might participate in the development of pronounced hypoxic impairments seen in the course of the observation period. It is recommended that adrenoblockers and inhibitors of synthesis of serotonin or serotonin-reactive structures may be used for correction of metabolic disorders.     

Differences in the strategies and potentials of human adaptation to hypoxia

The general patterns and individual specific features of human adaptation to acute hypoxic hypoxia caused by breathing a hypoxic oxygen-nitrogen gas mixture containing 8.0% oxygen have been studied. It was found that, at the initial stage of hypoxia, all examined subjects demonstrated a reduced oxygen consumption as compared to normoxia; then, this parameter increased and, beginning from a certain moment (after 5–15 min of exposure), exceeded the baseline level by 10–40%. Hypotheses explaining the mechanisms of this growth in oxygen consumption during hypoxia are considered. It has been found that the roles of the cardiovascular system and mechanisms of the tissue and cellular utilization of oxygen in the growth of the rate of oxygen consumption caused by hypoxia vary in different subjects. The hypothesis is put forward that the relatively low potential for rearrangement of the biological oxidation system at the cellular level, aimed at increasing the rate of oxygen consumption, predetermines a need to increase the rate of oxygen supply by the blood and, therefore, a greater strain of the cardiovascular system. In many cases, this strain can cause failure of adaptation to hypoxia. Other parameters that can serve as characteristics of a subject’s resistance to hypoxia, such as the intensity of EEG slow waves and the level of blood oxygenation, are also considered.     

Characteristics of Human Adaptation in the High Altitude of Central Asia and the Antarctic

The study involved healthy males that were not subject to prior training for resistance to hypoxia. Parameters of cardiac hemodynamics and vital lung capacity and red blood cell parameters were measured on days 35–40 of adaptation to altitudes of 3488–4000 m above sea level in the Pamir and Tien Shan mountains, as well as at the Vostok station, which is the remotest inhabited locality on earth, situated on the ice cover of the Antarctic. We were able to demonstrate that distinct functional and adaptation-related profiles developed at altitudes producing similar levels of hypoxia, but differing in the aggregate effect exerted by extreme natural and climatic factors. Of note, the functional reserves of the human organism measured after 5 weeks of adaptation were significantly lower for the high altitude of the Antarctic than for similar altitudes in Central Asia.     

Adaptive potential of operators with various dynamics of fitness for work during a transition from day to night shift]

While transferring from day to night shifts 3 categories of changes in the working ability are revealed among the operators. It is stated that the working ability in 19% of operators decreases, in 62%--remains practically unchanged, in 19%--improves. The higher levels of arterial pressure, vascular peripheral resistance (in both shifts), the heart systole rate (day shift) are found in the first group of operators. The structure of correlations between the physiological functions is characterized by harder intrasystemic relations in the day shift as against that of other operators and by the increasing effects of the intersystemic interactions while decreasing intrasystemic relations in the night shift. The adaptive potentialities were higher in the second group and particularly in the third group of operators.     

Principles of Physiological Regulation of the Body Functions in Incomplete Adaptation

The main condition of completing the process of adaptation of the body to the effect of an external factor is the return of the homeostatic system parameters to their initial levels or their stabilization at a new level. The article considers the state of incomplete adaptation (IA) based on the process of the stabilization of systemic reactions (respiration and blood circulation) on repeated exposure to extreme environmental factors (hypoxia and cold) associated with the excitation of the central regulatory mechanisms of the respiratory center system performing a compensatory–protective function. It is postulated that a change in the afferent information flows (the thresholds of excitation and reactivity of the peripheral receptor systems) forms the basis of IA. The IA state is supposed to persist for an indefinitely long period of time due to insufficient functional reserves and to be the cause of psychosomatic pathology.     

Ultraslow information control systems in the integration of life activity processes in the brain and body

The published data and the results of studies of the Department of Human Neurophysiology, revealing the place and importance of ultraslow information-control systems in the study of mechanisms for the integration of interorgan and intersystemic interactions, with the leading role of CNS and the autonomic nervous system, are summarized. The existing notions of the universality and commensurability of amplitude-time parameters, ultraslow bioelectric potentials (USBPs) recorded in the brain and the brain-controlled systems and organs have been considered. Experimental justifications for including one of the USBP types, a stable potential in the millivolt range in the vertex-tenar derivation (the omegametry method) in the psychophysiological approach are provided. This approach consists of choosing complementary integral psychological and physiological parameters permitting the study of the contingency of the mechanisms that control the functional state (wakefulness level) with specific features of the organization of higher mental functions and adaptive behavior, as well as in differentiating diagnostic markers: (a) the balance level and disintegration of intersystemic interaction in the body; and (b) disturbances of compensatory-adaptive possibilities and the adaptation reserve of the body. The prospects of using this approach in theoretical and applied studies on developmental psychophysiology, child psychoneurology, and functional neurology of chronic diseases of the nervous system have been considered.     

Respiratory control in aquatic insects dictates their vulnerability to global warming

Forecasting species responses to climatic warming requires knowledge of how temperature impacts may be exacerbated by other environmental stressors, hypoxia being a principal example in aquatic systems. Both stressors could interact directly as temperature affects both oxygen bioavailability and ectotherm oxygen demand. Insufficient oxygen has been shown to limit thermal tolerance in several aquatic ectotherms, although, the generality of this mechanism has been challenged for tracheated arthropods. Comparing species pairs spanning four different insect orders, we demonstrate that oxygen can indeed limit thermal tolerance in tracheates. Species that were poor at regulating oxygen uptake were consistently more vulnerable to the synergistic effects of warming and hypoxia, demonstrating the importance of respiratory control in setting thermal tolerance limits.     

Surgical anatomy of the gracilis muscle of the thigh

As demonstrates the investigation of 100 preparations, the main vascular-nervous "hilus" of the muscle is situated on the superior third of its lateral part. They contain the transversal branch of the medial artery, circumflexing the femoral bone with the accompanying vein, having the same name, and the anterior branch of the obturative nerve (92 preparations), or muscle branch of the femoral nerve (8 preparations). The muscle has a well developed network of intrasystemic and intersystemic anastomoses. Beginning from the first period of childhood, for sphincter plasticity either the whole muscle, or a graft, cut out from its lateral part, can be used.     

Electrophysiological Mechanisms of Adaptation Processes

A systemic analysis of the relationships between electrophysiological parameters of the cardiovascular and respiratory systems during adaptation processes has been performed in order to study some electrophysiological mechanisms of stress. Studies were performed in subjects with various circulatory disorders and in healthy subjects at rest and during exercise; in skilled and apprentice workers at an electronics plant; and in students under examination stress. It is demonstrated that determining the set of parameters of the integrated cardiac–respiratory–hemodynamic system is necessary but not sufficient for diagnosing stress and its individual stages. The main characteristic is the degree of harmony in the ratios between these parameters, i.e., the balance of relationships between subsystems; the ratios thereby serve as new diagnostic signs of the functional state of the body. A resonance–wave model of stress is proposed. This model forms a basis for the assessment of stress during its development, with the stages of strain and overstrain being regarded as stages of the positive dynamics of adaptation syndrome provided that self-regulation is preserved during the progress of these stages, i.e., resonance is formed. In the case of disharmonic ratios between electrophysiological parameters and imbalance of their relationships, the stages of adaptation processes differ in the degree of deviation from invariant ratios between parameters.     

Architectonics of the arteries of the latissimus dorsi muscle in humans and dogs

Vascularisation of musculus latissimus dorsi in man and dog was studied in 50 preparations. Methods of x-ray angiography, preparation and macro-microscopy of cleared preparations were used. The nutrition of the muscle was stated to carry out at the expense of the thoracodorsal artery and of the musculocutaneous branches of the intercostal arteries. Vascular-neuronal "gate" of the muscle is projected on the upper third of its lateral portions. A rich network of intrasystemic and intersystemic anastomoses makes it possible to switch off one or several sources of additional nutrition for the muscle. The most favourable conditions of blood supply exist for the muscle lateral portions which are reasonable to use for plastic purposes.     

Oxygen supply limits the heat tolerance of lizard embryos

The mechanisms that set the thermal limits to life remain uncertain. Classically, researchers thought that heating kills by disrupting the structures of proteins or membranes, but an alternative hypothesis focuses on the demand for oxygen relative to its supply. We evaluated this alternative hypothesis by comparing the lethal temperature for lizard embryos developing at oxygen concentrations of 10–30%. Embryos exposed to normoxia and hyperoxia survived to higher temperatures than those exposed to hypoxia, suggesting that oxygen limitation sets the thermal maximum. As all animals pass through an embryonic stage where respiratory and cardiovascular systems must develop, oxygen limitation may limit the thermal niches of terrestrial animals as well as aquatic ones.     

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Processing of leaf matter by lake-dwelling shredders at low oxygen concentrations

Organic sediments in freshwaters are regularly subject to low concentrations of oxygen. The ability of detritivores to sustain their feeding in such conditions should therefore be of importance for the decomposition process. In the present study, aquaria were used to determine processing rates of five lake-dwelling shredders at three different oxygen concentrations; normoxic (9 mg O₂ l^–1) and two levels of hypoxia (1 and 2 mg O₂ l^–1). Discs of alder leaves (Alnus glutinosa (L.)) were used as food. Four species of caddisfly larvae (Trichoptera Limnephilidae) and the isopod, Asellus aquaticus (L.) were compared in the experiments. Significant differences in processing rates per g animal biomass were found both at normoxia and 2 mg oxygen l^–1. At l mg O₂ l^–1 none of the invertebrates fed on leaf discs. The caddisfly larvae Halesus radiatus (Curtis), being one of the two most efficient shredders at normoxia, did not feed at 2 mg oxygen l^–1. The other species fed at rates 15–50 of that at normoxia. The least efficient shredder at normoxia, A. aquaticus was similar to two of the trichopterans at 2 mg O₂ l^–1. This study shows that the importance of specific shredder species may shift in case of hypoxia. Species-specific traits regarding oxygen sensitivity may also be influential for distribution patterns of shredder species both within and between lakes.     

Functional Body Capacities under the Conditions of Various Concentrations of Carbon Dioxide and Oxygen

We determined a permissible ratio between carbon dioxide and oxygen concentrations during accidental situations. The experiments (n = 138, 10 h each) on the effect of various concentrations of carbon dioxide and oxygen in the inhaled air were conducted on male volunteers aged 20–40 years subjected to a special medical examination. All experiments were divided into five series: hypercapnia + normoxia, hypercapnia + hyperoxia, hypercapnia + hypoxia, normocapnia + hypoxia, and ambient air (control). The results showed that functional capacities of the body are less impaired under the conditions of hypercapnia combined with hyperoxia. Thus, in accidental situations associated with rapid accumulation of carbon dioxide in the atmosphere of airtight chambers, a synchronous increase in pO₂ to 220–230 torr can provide for the highest work capacity.     

Physiological premises and mechanisms of normalizing effect of normobaric hypoxia and inhalation therapy]

Pathogenetic and physiological aspects of hypoxia problems have been considered. An opinion is stated that normalizing effect of intermittent normobaric hypoxia (INH) with short-term respiration of gaseous mixture containing at least 10% of oxygen in nitrogen is based on biorhythm inherent in all the living organisms with replacement of the high functional activity periods by the periods of rest and restoration with temporary physiological hypoxia as their typical companion. It is shown that for numerous diseases the course of INH or sessions of staying in the chamber of artificial mountain climate normalize the state of central nervous system, blood circulation, respiration, hemopoiesis and immunological reactivity, activate natural protective mechanisms and increase functional reserves of the organism. Allowing for anthropogenic pollution of the environment and its consequences for the health, it is advisable to widely adopt hypoxytherapy and orrhotherapy.     

Osteoclasts adapt to physioxia perturbation through DNA demethylation

Oxygen plays an important role in diverse biological processes. However, since quantitation of the partial pressure of cellular oxygen in vivo is challenging, the extent of oxygen perturbation in situ and its cellular response remains underexplored. Using two‐photon phosphorescence lifetime imaging microscopy, we determine the physiological range of oxygen tension in osteoclasts of live mice. We find that oxygen tension ranges from 17.4 to 36.4 mmHg, under hypoxic and normoxic conditions, respectively. Physiological normoxia thus corresponds to 5% and hypoxia to 2% oxygen in osteoclasts. Hypoxia in this range severely limits osteoclastogenesis, independent of energy metabolism and hypoxia‐inducible factor activity. We observe that hypoxia decreases ten‐eleven translocation (TET) activity. Tet2/3 cooperatively induces Prdm1 expression via oxygen‐dependent DNA demethylation, which in turn activates NFATc1 required for osteoclastogenesis. Taken together, our results reveal that TET enzymes, acting as functional oxygen sensors, regulate osteoclastogenesis within the physiological range of oxygen tension, thus opening new avenues for research on in vivo response to oxygen perturbation.     

Functional responses of adaptive consumers and community stability with emphasis on the dynamics of plant-herbivore systems

A comparatively recent focus in consumer–resource theory has been the examination of whether adaptive foraging by consumers, manifested through the functional response, can stabilize consumer–resource dynamics. We offer a brief synthesis of progress on this body of theory and identify the conditions likely to lead to stability. We also fill a gap in our understanding by analysing the potential for adaptively foraging herbivores, which are constrained by time available to feed and digestive capacity, to stabilize dynamics in a single-herbivore/two-plant resource system. Because foraging parameters of the adaptive functional response scale allometrically with herbivore body size, we parameterized our model system using published foraging data for an insect, a small mammal and a large mammal spanning four orders of magnitude in body size, and examined numerically the potential for herbivores to stabilize the consumer–resource interactions. We found in general that the herbivore–plant equilibrium will be unstable for all biologically realistic herbivore population densities. The instability arose for two reasons. First, each herbivore exhibited destabilizing adaptive consumer functional responses (i.e. density-independent or inversely density-dependent) whenever they selected a mixed diet. Secondly, the numerical response of herbivores, based on our assumption of density-independent herbivore population growth, results in herbivores reaching densities that enable them to exploit their resource populations to extinction. Our results and those of studies we reviewed indicate that, in general, adaptive consumers are unlikely to stabilize the dynamics of consumer–resource systems solely through the functional response. The implications of this for future work on consumer–resource theory are discussed.     

Studies on the interaction of leucocytes and the myocardial vasculature

Granulytes play an important role in increasing the infarct size after ischemia and reperfusion by the release of oxygen-derived free radicals (ODFR) and lysosomal enzymes. It has been shown that the number of granulocytes adhering to the vascular endothelium increases after occlusion of the coronary artery, and that the area of myocardial damage can be reduced by preventing granulocyte adherence with monoclonal antibodies directed against adhesion receptors. The underlying mechanism of granulocyte activation under these conditions is not yet known. We have investigated whether granulocytes can be activated directly by reduced oxygen tensions. Granulocytes were suspended in a hypoxic buffer and incubated on fibronectin and gelatin coated microtitre plates at 1–3% ambient oxygen to study their ability to adhere to these matrices. The results showed that the adherence of granulocytes to fibronectin was dependent on the duration of hypoxia. After 30 min of incubation under hypoxia granulocyte adherence increased 1.3 to 1.8 fold compared to the normoxic control. The adherence to fibronectin could be inhibited partially by anti-CD18 antibody, a monoclonal antibody to the common beta chain of a class of extracellular matrix receptors. This direct activation of granulocytes due to hypoxic conditions may have implications for the interaction of these cells with the vascular endotheliumin vivo, (Mol Cell Biochem116: 197–202, 1992)