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.     

A proposed classification of environmental adaptation: the example of high altitude

Extreme environments are defined as the opposite of usual environments where the evoked physiological responses are unperceivable, repeatable and adjusted to the constraint. Adaptation strategies to a given environment show three levels: cultural or technological, where a buffer space is built to protect the organism from the hostile milieu, physiological, where temporary adaptive mechanisms are developed, and genetic, where full adaptation is possible with normal life and reproduction. The cost of adaptation increases from the genetic level (minimal cost) to the technological level. These concepts are illustrated by the example of adaptation to altitude hypoxia. The technological level is given by the use of oxygen bottles by high altitude climbers. The physiological level involves various physiological and biological systems (increase in heart rate, ventilation, erythropoiesis, expression of hypoxia-inducible factors, etc.). The genetic level has been reached by some animal species such as Yaks, Llamas, Pikas but has not yet been demonstrated in humans. Diseases developed during exposure to acute or chronic hypoxia may be considered as “adaptive crises” that mimic the transition to a lower energy level of adaptation.     

Complex estimation of adaptation abilities of the organism in children using the indices of responsiveness of the cardiovascular system and characteristics of EEG

Based on the complex analysis of the data of cardiointervalographic (CIG) and rheoencephalographic (REG) examination of 37 healthy children and 63 children suffering from bronchial asthma (BA), we identified the most informative indices characterizing reactions of the cardiovascular system under conditions of an active orthostatic test (coefficient of autonomic responsiveness and index of responsiveness of the vessels). We conclude that the relation between the values of these indices allows one to identify the level of strain of the regulatory mechanisms and the state of the adaptation systems of the organism, which determine the adequacy of control of the autonomic sphere. The following gradations can be classified: an optimum level, compensated adaptation disorders (strain and overstrain of the regulatory mechanisms), and decompensated adaptation disorders (exhaustion of the regulatory mechanisms and failure of adaptation). Among clinically healthy children, we found a risk group (about 30%) with manifestations of lowering of the organism’s adaptive abilities. It is shown that groups of healthy children and children suffering from BA differ from each other in the shares of different patterns of EEG and variants of EEG responses to a hyperventilation test. Qualitative and quantitative characteristics of EEG in children, despite high interindividual variability, clearly correlate with the state of adaptation processes. The expedience of a complex approach in estimating the adaptation ability of the child based on the data of CIG, REG and EEG examinations is discussed. Neirofiziologiya/Neurophysiology, Vol. 38, No. 1, pp. 72–84, January–February, 2006.     

Awareness of Sensorimotor Adaptation to Visual Rotations of Different Size

Previous studies on sensorimotor adaptation revealed no awareness of the nature of the perturbation after adaptation to an abrupt 30° rotation of visual feedback or after adaptation to gradually introduced perturbations. Whether the degree of awareness depends on the magnitude of the perturbation, though, has as yet not been tested. Instead of using questionnaires, as was often done in previous work, the present study used a process dissociation procedure to measure awareness and unawareness. A naïve, implicit group and a group of subjects using explicit strategies adapted to 20°, 40° and 60° cursor rotations in different adaptation blocks that were each followed by determination of awareness and unawareness indices. The awareness index differed between groups and increased from 20° to 60° adaptation. In contrast, there was no group difference for the unawareness index, but it also depended on the size of the rotation. Early adaptation varied between groups and correlated with awareness: The more awareness a participant had developed the more the person adapted in the beginning of the adaptation block. In addition, there was a significant group difference for savings but it did not correlate with awareness. Our findings suggest that awareness depends on perturbation size and that aware and strategic processes are differentially involved during adaptation and savings. Moreover, the use of the process dissociation procedure opens the opportunity to determine awareness and unawareness indices in future sensorimotor adaptation research.     

Role of nitric oxide in adaptation to hypoxia and adaptive defense

Adaptation to hypoxia is beneficial in cardiovascular pathology related to NO shortage or overproduction. However, the question about the influence of adaptation to hypoxia on NO metabolism has remained open. The present work was aimed at the relationship between processes of NO production and storage during adaptation to hypoxia and the possible protective significance of these processes. Rats were adapted to intermittent hypobaric hypoxia in an altitude chamber. NO production was determined by plasma nitrite/nitrate level. Vascular NO stores were evaluated by relaxation of the isolated aorta to diethyldithiocarbamate. Experimental myocardial infarction was used as a model of NO overproduction; stroke-prone spontaneously hypertensive rats (SHR-SP) were used as a model of NO shortage. During adaptation to hypoxia, the plasma nitrite/nitrate level progressively increased and was correlated with the increase in NO stores. Adaptation to hypoxia prevented the excessive endothelium-dependent relaxation and hypotension characteristic for myocardial infarction. At the same time, the adaptation attenuated the increase in blood pressure and prevented the impairment of endothelium-dependent relaxation in SHR-SP. The data suggest that NO stores induced by adaptation to hypoxia can either bind excessive NO to protect the organism against NO overproduction or provide a NO reserve to be used in NO deficiency.     

Respiratory response to chemical stimuli and exercise capacity under conditions of acute hypoxia in elite mountain climbers]

To investigate the factors that modulate exercise performance at extreme altitude, the role of the following variables was analyzed in 16 climbers: 1) ventilatory response to chemical stimuli (hypoxia and hypercapnia); and, 2) maximum exercise performance while breathing room air and during acute hypoxia (F1O2, 0.11). Seven climbers (elite climbers, AE) had previously ascended to 8,000 m or more above sea level, and 9 (A) had never achieved such extreme altitude. Then healthy sedentary subjects (C) of similar age (31.1 +/- 6.0 SD years) were used as control group. Elite climbers showed higher ventilatory responses to both transient hypoxia (-0.49 +/- 0.13 L x min-1 x %-1) (p less than 0.05) and progressive hypoxia (-0.47 +/- 0.13 L x min-1 x %-1) than C (-0.33 +/- 0.14 and -0.30 +/- 0.15 L x min-1 x %-1, respectively). By contrast, no differences were observed between the two groups of climbers. The ventilatory response to hypercapnia was higher in AE (3.04 +/- 1.03 L x min-1 mmHg-1) compared to A (1.85 +/- 0.73 L x min-1 mmHg-1) (p less than 0.05) but similar to that observed in C. Breathing 11% O2, maximum workload and oxyhemoglobin desaturation during maximum exercise were similar in both groups of climbers. Additionally, the ventilatory response to hypoxia did not correlate with maximum workload (F1O2, 0.11), maximal ventilation during exercise (F1O2, 0.11), nor with the altitude score. The present study supports previous reports that inform about the role of the ventilatory response to hypoxia in the exercise performance at high altitude.(ABSTRACT TRUNCATED AT 250 WORDS)     

Functional capacity of the cardiovascular system of elderly people as estimated by heart rate variability

With the aid of mathematical and spectral analysis of the heart rate (HR) wave structure in a dynamic interval tachogram (TG) in elderly subjects, it has been shown that a stable sinus rhythm is typical of the majority of the indigenous population of the rural areas of the North aged 78–97 years and migrants living in the city of Vorkuta aged 60–88 years. The total RR-interval spectrum power (800 ± 98 ms²) in the TGs of the native population is shifted to the very low frequency band (VLF, 52%), which indicates predomination of the humoral-metabolic HR regulation level. The reaction to orthostatic load in elderly subjects is characterized by a significant increase in the total spectrum power, which indicates changes in the autonomic balance of regulation of the wave structure of the HR variability. A low total spectrum power (609 ± 104 ms²) with a predominance of low frequency (LF) waves in the TGs of the migrants at rest reflects the activity of the sympathetic component of HR regulation. The reduction of the parasympathetic regulation and the growth of the sympathetic activity during an active orthostatic test in the migrants is a predictor of cardiovascular diseases. In individual TGs of recipients with HR disorders, the orthostatic test (the redistribution of blood flow in the main vessels) results in a decrease in the number of extrasystoles due to the specific features of the baroreflex regulation mechanisms of the cardiovascular system. The HR variability has been shown to be an indicator of the functional capacity of the cardiovascular system in elderly subjects.     

Mechanisms of post-flight orthostatic intolerance

Post-flight orthostatic intolerance is a dramatic physiological consequence of human adaptation to microgravity made inappropriate by a sudden return to 1-G. The immediate mechanism is almost always a failure to maintain adequate tissue perfusion, specifically perfusion of the central nervous system, but vestibular dysfunction may occasionally be the primary cause. Orthostatic intolerance is present in a wide range of clinical disorders of the nervous and cardiovascular systems. The intolerance that is produced by spaceflight and 1-G analogs (bed rest, head-down tilt at a moderate angle, water immersion) is different from its clinical counterparts by being only transiently present in subjects who otherwise have normal cardiovascular and regulatory systems. However, the same set of basic pathophysiological elements should be considered in the analysis of any form of orthostatic intolerance.     

Current problems of space cardiology

The development of space cardiology is considered, from the first flights of animals and humans to the studies conducted on board International Space Station (ISS). The material is recounted in four sections in accordance with the theoretical statements presented in the book “Space Cardiology” (1967). The first section is analysis of rearrangement of blood circulation under the conditions of microgravity. Long-term microgravity has been demonstrated to require mobilization of additional functional reserves of the body. During the first six months of the flight, the cardiovascular homeostasis is supported by the regulatory mechanisms of the blood circulation system, whereas in the case of a more prolonged impact of microgravity, intersystem control is actively involved (suprasegmental divisions of autonomic regulation). In the second section dealing with the roles of the right and left divisions of the heart in adaptation to microgravity of the cardiovascular system, the important role of the right heart at the initial stage of a space flight (SF) is emphasized. The third section addresses the problem of reducing the orthostatic stability; this study has been initiated as early as the first manned space flights. The results obtained on board ISS testify to the importance of evaluating the functional reserves of the blood circulation system. The fourth section presents data on the new methods of myocardial examination that are to be soon introduced into SF medical provision. In conclusion, some new projects in space cardiology are discussed.     

Nutritional alterations at high altitude in man

During the French 1980 Mount Pabil (7,102 m) Expedition, a study was made of four altitude-acclimatised climbers (age 36.5 +/- 3.6 years; VO2max 50.5 +/- 3.1 ml X kg-1). Intake of various nutrients, body weight, skinfold thicknesses as indices of body composition, and water and nitrogen balances, were recorded before, and during high altitude exposure, and again after the return to low altitude. There was a significant (35-57%) reduction in total caloric intake at high altitude. Body weight decreased progressively, mainly due to a reduction in body fat. The subjects apparently remained in water balance, while the nitrogen balance was always negative during high altitude exposure. The significant nutritional alterations were mainly observed above 6,000 m. They are discussed with respect to changes in feeding patterns and in hormonal status of the climbers accompanying hypoxia and other stressors proper to high altitude.     

Effect of hypoxic hypoxia on immune reactivity and some factors of nonspecific resistance of humans and animal organisms]

Evidences available in home and foreign literature concerning the effect of normobaric hypoxia, adaptation to mountain climate conditions and trainings in barochamber on cellular and humoral indices of immunity have been critically considered. The data on the influence of permanent residence under mountain conditions on the level of sickness rate of population, bioenergy indices, and activity of the opiate brain system have been studied as well. The analyzed data indicate that it is expedient to use normobaric hypoxia for effects on the state of immunic organism system.     

Role of dopamine in the peripheral mechanisms of respiration control

Under clinical conditions, we studied the interaction between dopamine (DA) metabolism and hypoxia stimulationrelated ventilatory responses (HVR) before and after adaptation to periodical hypoxic episodes. Thirty-seven young and elder persons were tested; among elder tested subjects there were patients with Parkinson’s desease treated or not treated with DOPA-DA precursor-containing drugs (levoDOPA/carbiDOPA). We measured the HVR indices and DA and DOPA contents in the venous blood of tested persons before and after a 14-day-long hypoxic training. The highest indices of the ventilation sensitivity to hypoxia together with the lowest above-mentioned chemical indices were observed in young persons. An increase in the DA and DOPA levels in the venous blood were observed concurrently with suppression of the ventilation responses to hypoxic episodes. After a course of periodical hypoxic sessions, we observed in all groups opposite dynamics of DA and DOPA metabolism. An increase in the DA level in young persons and a trend toward its decrease in older healthy persons and parkinsonian patients was nevertheles accompanied by an HVR increase in all groups. Possible relations between the DA metabolism indices and peripheral mechanisms of respiratory control are discussed.     

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.     

Cardiorespiratory responses of animals to passive orthostasis after intermittent hypoxia during head-down tilt

Cardiorespiratory responses induced by upright tilt before and after intermittent hypoxia during head-down tilt, were investigated in rabbits. Arterial blood pressure, heart rate, central venous pressure, transmural filling pressure of the heart (calculated as the product of esophageal and central venous pressure), breathing frequency, esophageal pressure were measured in supine (baseline), head-down and upright posture. Our results indicate a reduction in orthostatic responses in cardiovascular system after intermittent hypoxia.     

Late EEG after-effects in humans following hyperventilation. II. A comparison between subjects with different level of adaptation to hypoxia

The late EEG after-effects following application of a short-lasting ventilatory interoceptive influence (3 min hyperventilation-HV) were studied in humans with three degrees of adaptation: students (ST) with a lower degree of training, professional alpine climbers with a high level of training (AL1) and the same subjects (AL2) in a middle position of adaptation i.e. 6 months after an expedition. ST developed late EEG after-effects, consisting mainly in an increase of the beta-2 EEG activity; AL1 showed very slight changes, while in AL2 the EEG after-effects were intermediate. It is suggested, that a lower level of adaptation facilitates the triggering through HV of processes in the cortical EEG which accompany an improvement of the brain tone.     

Cardiorespiratory response to exercise in men repeatedly exposed to extreme altitude

The ventilatory and heart rate responses to exercise were studied in four experienced high-altitude climbers at sea level and during a 6-wk period above 4,500 m to discover whether their responses to hypoxia were similar to those of high-altitude natives. Comparison was made with results from four scientists who lacked their frequent exposure to extreme altitude. The climbers had greater Vo2max at sea level and altitude but similar ventilatory responses to increasing exercise. On acute hypoxia at sea level their ventilatory response was less than that of scientists. Their heart rate response did not differ from that of scientists at sea level, but with acclimatization the reduction in response was significantly greater. Alveolar gas concentrations were similar after acclimatization, but climbers achieved these changes more rapidly. The increase in hematocrit was similar in the two groups. It is concluded that these climbers, unlike high-altitude residents, have cardiorespiratory responses to exercise similar to those of other lowlanders except that their ventilatory response was lower and the reduction in their heart rate response was greater.     

Cardiovagal regulation during combined hypoxic and orthostatic stress: fainters vs. nonfainters.

We tested the hypothesis that individual differences in the effect of acute hypoxia on the cardiovagal arterial baroreflex would determine individual susceptibility to hypoxic syncope. In 16 healthy, nonsmoking, normotensive subjects (8 women, 8 men, age 20-33 yr), we assessed orthostatic tolerance with a 20-min 60 degrees head-upright tilt during both normoxia and hypoxia (breathing 12% O(2)). On a separate occasion, we assessed baroreflex control of heart rate (cardiovagal baroreflex gain) using the modified Oxford technique during both normoxia and hypoxia. When subjects were tilted under hypoxic conditions, 5 of the 16 developed presyncopal signs or symptoms, and the 20-min tilt had to be terminated. These "fainters" had comparable cardiovagal baroreflex gain to "nonfainters" under both normoxic and hypoxic conditions (normoxia, fainters: -1.2 +/- 0.2, nonfainters: -1.0 +/- 0.2 beats.min(-1).mmHg(-1), P = 0.252; hypoxia, fainters: -1.3 +/- 0.2, nonfainters: -1.0 +/- 0.1 beats.min(-1).mmHg(-1), P = 0.208). Furthermore, hypoxia did not alter cardiovagal baroreflex gain in either group (both P > 0.8). It appears from these observations that hypoxic syncope results from the superimposed vasodilator effects of hypoxia on the cardiovascular system and not from a hypoxia-induced maladjustment in baroreflex control of heart rate.     

Production and storage of nitric oxide in adaptation to hypoxia.

Adaptation to hypobaric hypoxia is known to exert multiple protective effects related with nitric oxide (NO). However the effect of adaptation to hypoxia on NO metabolism has remained unclear in many respects. In the present work we studied the interrelation between NO production and storage in the process of adaptation to hypoxia. The NO production was determined by the total nitrite/nitrate concentration in rats plasma. The volume of NO store was evaluated in vitro by the magnitude of isolated aorta relaxation to diethyldithiocarbamate. It was shown that both the nitrite/nitrate level and the NO store increased as adaptation to hypoxia developed. Furthermore, the NO store volume significantly correlated with plasma nitrite/nitrate. Therefore, adaptation to hypoxia stimulates NO production and storage and these effects can potentially underlie NO-dependent beneficial effects of adaptation.     

Effect of 4 hours HD -6 degrees on heart rate variability in symptomatic and non symptomatic subjects

Orthostatic intolerance is the most serious symptom of cardiovascular deconditioning induced by microgravity exposure. In fact the neural control mechanisms of the cardiovascular system are significantly affected by this condition. Non-invasive measurement of Heart Rate Variability (HRV) have been used as a valuable tool to characterize the ability of neuroendocrine regulatory systems to modulate the cardiovascular function by analyzing the spontaneous fluctuations of arterial pressure and heart period on a beat-to-beat basis. Concerning this, conflicting results have been reported on the heart rate and blood pressure variability responses during exposure to microgravity. These differences seem to be due to different experimental designs used. Moreover, the different behavior of normal subjects in response to orthostatic stress after HD, i.e. Symptomatic (S) or Non Symptomatic (NS), could play some roles in producing these discrepancies. Therefore the aim of the present study was to examine BP and HR variability before and after 4 hours of HD in two groups of normal subjects with and without symptoms of orthostatic intolerance to orthostatic stress.     

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.