Regulation of External Respiration and Gas Exchange during a 20-Day Exposure to Sessions of Intermittent Normobaric Hypoxia

A study was made of the effects of a 20-day course of intermittent normobaric hypoxia (INH) on the parameters of gas exchange and the regulation of respiration in healthy volunteers. A phasic change in oxygen consumption at rest was observed: it decreased on the 10th day of the INH course and increased on the 20th day, with a parallel increase in the efficiency of pulmonary ventilation. According to the hypercapnic test, the ventilatory response threshold decreased, whereas ventilatory sensitivity increased; these effects were most pronounced during the first ten days of INH training and still detectable in recovery. It was assumed that the first phase of training (up to the tenth day) is associated with compensatory activation of pulmonary ventilation owing to an increase in peripheral and central chemosensitivity to the CO₂ stimulus. In the second phase, which was associated with further slight changes in the parameters of external respiration, the gas exchange level is restored owing to an adaptive increase in efficiency of oxygen utilization in cells and tissues.     

Intermittent Normobaric Hypoxia as a Model of Incomplete Adaptation

The Neirokartograf software was used to calculate the correlations between EEG, external respiration, and gas exchange parameters recorded in the initial state, after 10 or 20 sessions of intermittent normobaric hypoxia (INH), and after its cessation. It was demonstrated that cerebral structures were increasingly involved in gas exchange control in ascending order during the course of INH sessions. The artificial short-term extreme exposure followed by a return to usual conditions resulted in incomplete adaptation. Even 20 days after the cessation of INH sessions, neurodynamics did not return to the initial state.     

Extension of the Functional Range of Respiratory and Gas Exchange Responses in Repetitive Hypoxia

External respiration and gas exchange were studied in healthy volunteers during a session of intermittent normobaric hypoxia (INH) consisting of three cycles of breathing alternately a hypoxic mixture (10.7% O₂) for 5 min and normal air for 5 min. The ventilatory response increased in the successive cycles of hypoxia and gradually decreased during the normoxic intervals. These changes were accompanied by an increase in carbon dioxide in lung air, which was not eliminated by the increased pulmonary ventilation during the hypoxic intervals. However, the mean oxygen consumption did not change during the INH session because the ventilatory reactivity and breathing depth, as well as the efficiency of oxygen utilization, increased from cycle to cycle.__________Translated from Fiziologiya Cheloveka, Vol. 31, No. 3, 2005, pp. 100–107.Original Russian Text Copyright © 2005 by Krivoshchekov, G. Divert, V. Divert.     

Comparative analysis of gas exchange and cardiorespiratory system responses of swimmers and skiers to increasing normobaric hypoxia and physical load

Qualification-comparable groups of young men engaged in cyclic kinds of sports were tested using a stepwise increasing load on a bicycle ergometer and 25-min exponentially increasing normobaric hypoxia to a final oxygen concentration of 10%. Skiers, who had the greatest values of maximal oxygen consumption during muscular work, showed relaxed cardiorespiratory reactions and a greater decrease in hemoglobin saturation with oxygen in hypoxia. Swimmers, whose ventilatory function in the course of trainings was restricted, developed preadaptation to hypoxia, with changes in external respiration and gas exchange functions, which allowed better saturation of blood with oxygen in lungs during hypoxia. The joint assessment of the aerobic capacity during physical work and physiological responses to hypoxia showed a direct correlation between the individual maximal oxygen consumption and the rate of decrease in the blood hemoglobin saturation in increasing hypoxia, which may be promising for assessing the functional state of athletes and its correction during training.     

Cardiorespiratory effects of prolonged angiotensin II block in resting conscious dogs

Intravenous (iv) infusion of the angiotensin II (ANG II) receptor blocker saralasin in resting conscious dogs during physiological pertubations, such as hypotension and prolonged hypoxia, indicates the presence of an ANG II drive to increase respiration and decrease the arterial partial pressure of CO2 (PaCO2). In contrast, in eupneic resting dogs on a regular chow diet, iv infusion of saralasin for short periods (up to 30 min) provides no evidence of a tonic effect of circulating levels of ANG II on acid-base balance, respiration, metabolism, or circulation. However, ANG II influences physiological processes involving salt, water, and acid-base balances, which are potentially expressed beyond a 30 min time period, and could secondarily affect respiration. Therefore, we tested the hypothesis that blocking ANG II with iv saralasin would affect respiration and circulation over a 4-h period. Contrary to the hypothesis, iv infusion of saralasin in resting conscious eupneic dogs on a regular chow diet over a 4-h period had no effects on plasma strong ions, osmolality, acid-base balance, respiration, metabolism, or circulation when compared with similar control studies in the same animals. Thus, ANG II does not play a tonic modulatory role in respiratory control under "normal" physiological conditions.     

Effect of Short-Term Intermittent Normobaric Hypoxia on the Regulation of External Respiration in Humans

Baseline external respiration and gas exchange values, as well as ventilatory thresholds and sensitivity to the O₂ and CO₂ stimuli in hypoxic and hypercapnic tests, were measured 1 h before and after a session of intermittent normobaric hypoxia (INH) (six repetitions with a 5-min inhalation of a gas mixture (10% O₂) alternating with a 3-min inhalation of atmospheric air). After an INH session, the background CO₂ level in the lungs increased by 10%. In the hypercapnic test, the actuation threshold of the ventilatory response did not change, whereas ventilatory sensitivity increased. The maximal pulmonary ventilation and the corresponding critical CO₂ level in the lungs also increased at the end of the test. In the hypoxic test, the ventilatory response occurred at a decreased level of blood oxygenation after an INH session, the pulmonary ventilation level being decreased and the CO₂ content in the lungs being increased at the end of the test. The data obtained evidence the maintenance of changed gas homeostasis for 1 h after an INH session. In this process, control of respiration was effected, with the hypoxic drive being weakened and the peripheral chemoreceptor sensitivity being decreased. The hypercapnic drive also increased, which may be determined by readjustment in the central mechanisms of respiratory regulation.     

Behavioral and physiological compensation for chronic hypoxia in the sailfin molly (Poecilia latipinna)

This study demonstrates that short-term behavioral and physiological responses may permit the sailfin molly Poecilia latipinna to cope successfully with extreme hypoxia and suggests an interaction between behavioral response (aquatic surface respiration [ASR]) and physiological compensation. Poecilia latipinna acclimated to chronic hypoxia (6 wk at 1.0 mg L(-1) O(2)) exhibited higher hemoglobin and red blood cell concentrations and a 17%-19% lower critical oxygen tension than fish acclimated to normoxia. Ventilation frequency increased twofold under acclimation to hypoxia, a response that did not diminish with time. However, the use of ASR was an immediate response to hypoxia that decreased over the acclimation period. This suggests that gradual physiological compensation decreases the threshold for ASR. There was no consistent effect of hypoxia on mortality and no effect of hypoxia treatment on the number of gestating females, suggesting that plastic behavioral and physiological responses in P. latipinna compensate for hypoxia to a degree that mitigates a decrease in survivorship and facilitates continued reproduction in a laboratory setting. However, there may be predation costs in the field related to ASR.     

植物低氧胁迫伤害与适应机理的研究进展

不良的通气条件导致了正常生长发育的植物生理性缺氧,低氧胁迫是高等植物主要的非生物胁迫因素之一。本文综述了低氧胁迫对植物生长、植株形态的影响,低氧胁迫对植物内部水分、养分吸收的变化,呼吸代谢途径的变化、激素代谢的变化,氧化系统的变化的影响,以及低氧胁迫过程中植物体内信号的传导、基因的表达、蛋白质的合成等,在不同层面分析了低氧胁迫对植物的伤害及植物对低氧逆境适应机理的最新研究成果。     

The effect of different regimens of interval hypoxic training on the cardiorespiratory and hematological functions

Physiological changes in the human organism are observed in different regimens of interval hypoxia. They are dependent on several factors, including the strength of the hypoxic stimulus used (oxygen percentage of the air inhaled), time intervals of some hypoxic positions, duration of the periods of normal respiration, and the total number of the recurrent hypoxic exposures or the total duration of the hypoxic exposure during a day [1–4]. By changing the selected parameters of the hypoxic load, it is possible to exert the necessary effect on particular physiological functions and to directly affect the main metabolic reactions of the organism. This opens up new fields for the interval hypoxic exposures used as therapy for and preventive treatment of different diseases [5–8], and for improving human health and increasing labor productivity [9–13]. The sports training effect is caused by the combined effects resulting from changes in certain parameters of the physical load. When using artificially induced interval hypoxia, it is possible to provide different regimens of physiological effects as is done in sports training. That is the reason these regimens, proposed by the pioneers of this method, are called interval hypoxic training [14–18]. The objective of this paper is to study the effect of different regimens of interval hypoxia on the cardiorespiratory and hematological functions of athletes in order to use the data obtained to optimize interval hypoxic training.     

Adaptations of fish species to oxygen depletion in a central Amazonian floodplain lake

Pronounced seasonal and daily oxygen concentration changes are characteristic for Amazonian floodplain lakes. Studies on the fish fauna of the Lago Camaleão, Solimões River, Amazonas, Brazil, showed several fish species which are able to survive prolonged periods of heavy hypoxia. Twenty species belonging to eight families were observed in the laboratory in order to determine their respiratory adaptations to hypoxic conditions and oxygen concentrations at which the fish present respiratory adaptations. Finally, the fish species were distributed throughout the habitats of Lake Camaleão according to their adaptation responses. Ten fish species used the surface water for aquatic surface respiration, four species used atmospheric oxygen for aerial respiration, four species used oxygen supplied by the exudation of the roots of floating macrophytes and two exhibited a high tolerance to hypoxic conditions, and well-developed physiological biochemical mechanisms. The fish fauna is well adapted to low oxygen concentrations. The large variety of morpho-anatomical adaptations associated with biochemical and physiological mechanisms to tolerate hypoxic and anoxic conditions enable the 20 fish species to exploit several habitats of Lago Camaleão, such as floating aquatic macrophyte meadows, open water and near the shoreline.     

Compensatory and adaptive rearrangement in the human respiratory system under acute hypoxic conditions

Relationships between the parameters of external respiration (minute volume and respiration rate) and those of internal, tissue respiration (oxygen consumption, arteriovenous oxygen difference and efficiency of oxygen uptake) were studied during a period of acute hypoxia and upon its completion. The subjects were exposed to hypoxia for 25 min using oxygen-nitrogen hypoxic gas mixtures (HGMs) differing in oxygen content (8 and 12%, HGM-8 and HGM-12, respectively). From the third to the fifth minutes of exposure to HGM-8, the respiration minute volume (RMV) was found to increase by 51 ± 33% as compared to the background value; however, the body’s oxygen consumption (OC) was 35 ± 22% reduced. Afterwards, OC grew to reach, from the 20th to the 25th min of hypoxia, 108 ± 21% of the background value and 181% of the value determined from the third to the fifth minutes of hypoxia. OC growth was accompanied by an insignificant RMV increase (by 12%) as compared to the level determined from the third to the fifth minutes of hypoxia, whereas the efficiency of oxygen uptake from the arterial blood increased by 75% for the same period. RMV growth from the third to the fifth minutes of hypoxia occurred as expense result of a higher breathing depth; at the same time, the respiration rate decreased as compared to the background value. By the period from the 20th to the 25th min of exposure to HGM-8, the respiration rate increased by 21% as compared to the period from the third to the fifth minutes of hypoxia. The efficiency of oxygen uptake from the arterial blood remained higher than the background value for at least 5 min after completion of the exposure to HGM-8. During the same period, the ventilation equivalent, an indicator of the efficiency of external respiration, i.e., of oxygen supply to the body, was significantly lower than the background value. During the exposure to HGM-12, RMV increased to a lesser extent than on exposure to HGM-8, however, the efficiency of oxygen uptake was higher during exposure to HGM-12; therefore, OC was also higher in the latter case. Therefore, the assumption that, during hypoxia, intensified external respiration (ventilatory response) itself compensates oxygen deficiency in inhaled air is revised. Ventilatory response is only a portion of the entire functional system of respiration (both external and tissue respiration). The role of ventilatory response is important for conditioning the tissue respiration rearrangement to eliminate deficiency of oxygen consumption during hypoxia. The retained higher oxygen uptake from the arterial blood during the period after completion of hypoxic treatment testifies to the adaptive implication of changes in tissue respiration; the same is confirmed by a reduced ventilation equivalent after hypoxia, which is indicative of the growing efficiency of external respiration, i.e., of an improved oxygen supply to the body.     

Intrasystemic and Intersystemic Rearrangements of Physiological Parameters in Experimental Acute Hypoxia

Simultaneous computer recording of the parameters of external respiration, systemic and cerebral blood circulation, arterial pressure, oxygen saturation of hemoglobin, and tissue oxygen tension has been used to study the intrasystemic and intersystemic rearrangements at different stages of acute hypoxia caused by breathing hypoxic oxygen–nitrogen mixtures containing 6.8–8.0% oxygen. It has been found that all main vital systems of the body are involved in the response to hypoxia; however, the degree of their involvement and the changes in individual parameters vary considerably in different subjects. The functional strain of some systems may remain almost constant throughout the period of hypoxia, whereas the strain of others may gradually increase or decrease. It has been found that each stage of hypoxia is characterized by certain limits of the strain (involvement) of the functional reserves of oxygen supply systems; if the functional strain goes beyond these limits, then either intrasystemic and intersystemic relationships are disorganized or compensation reserves are overspent and the time of tolerance to hypoxia is decreased.     

Respiratory responses to short term hypoxia in the snapping turtle, Chelydra serpentina

Among vertebrates, turtles are able to tolerate exceptionally low oxygen tensions. We have investigated the compensatory mechanisms that regulate respiration and blood oxygen transport in snapping turtles during short exposure to hypoxia. Snapping turtles started to hyperventilate when oxygen levels dropped below 10% O(2). Total ventilation increased 1.75-fold, essentially related to an increase in respiration frequency. During normoxia, respiration occurred in bouts of four to five breaths, whereas at 5% O(2), the ventilation pattern was more regular with breathing bouts consisting of a single breath. The increase in the heart rate between breaths during hypoxia suggests that a high pulmonary blood flow may be maintained during non-ventilatory periods to improve arterial blood oxygenation. After 4 days of hypoxia at 5% O(2), hematocrit, hemoglobin concentration and multiplicity and intraerythrocytic organic phosphate concentration remained unaltered. Accordingly, oxygen binding curves at constant P(CO(2)) showed no changes in oxygen affinity and cooperativity. However, blood pH increased significantly from 7.50+/-0.05 under normoxia to 7.72+/-0.03 under hypoxia. The respiratory alkalosis will produce a pronounced in vivo left-shift of the blood oxygen dissociation curve due to the large Bohr effect and this is shown to be critical for arterial oxygen saturation.     

Effects of nitric oxide and peroxynitrite on the cytochrome oxidase K(m) for oxygen: implications for mitochondrial pathology

This review summarises current knowledge about the effect of oxygen on cytochrome oxidase activity in vitro and in vivo. Cytochrome oxidase normally operates above its K(m) for oxygen in vivo. However, decreases in the intracellular oxygen concentration (hypoxia) under physiological extremes, or during pathophysiology, can cause mitochondrial respiration to become oxygen limited. Inhibitors that raise the enzyme's K(m) will induce oxygen limitation under apparently normoxic conditions. It is known that the concentrations of nitric oxide and peroxynitrite are raised in a number of pathophysiological conditions. These compounds are capable of reversibly and irreversibly raising the cytochrome oxidase K(m) for oxygen. Therefore, measurements of cell and mitochondrial respiration in vitro that fail to systematically vary oxygen through the range of physiological concentrations are likely to underestimate the effects of nitric oxide and peroxynitrite in vivo.     

Ecomorphological adaptation to oxygen deficiency in Amazon floodplains by serrasalmid fish of the genus Mylossoma

Serrasalmids of the genus Mylossoma are obligate gill-breathers that are encountered in the floodplain lakes of Amazonia, even when the oxygen concentrations there are below 0^.5 mg l⁻¹. It was shown by experiments that fish of these species are capable of utilizing the oxygen-rich surface layer of the water for respiration, in order to survive periods of habitat-induced hypoxia. This so-called aquatic surface respiration entails an increase in locomotory activity and an ecomorphosis involving the formation of a dermal extension on the lower jaw, that apparently has a hydrodynamic function for using the surface layer for gill respiration; when the water is aerated, it retrogresses to its original size. Histological examination showed that the extension is formed by edematous processes in the stratum spongiosum.     

Activation of Hsp90-eNOS and increased NO generation attenuate respiration of hypoxia-treated endothelial cells

Hypoxia induces various adoptive signaling in cells that can cause several physiological changes. In the present work, we have observed that exposure of bovine aortic endothelial cells (BAECs) to extreme hypoxia (1-5% O(2)) attenuates cellular respiration by a mechanism involving heat shock protein 90 (Hsp90) and endothelial nitric oxide (NO) synthase (eNOS), so that the cells are conditioned to consume less oxygen and survive in prolonged hypoxic conditions. BAECs, exposed to 1% O(2), showed a reduced respiration compared with 21% O(2)-maintained cells. Western blot analysis showed an increase in the association of Hsp90-eNOS and enhanced NO generation on hypoxia exposure, whereas there was no significant accumulation of hypoxia-inducible factor-1alpha (HIF-1alpha). The addition of inhibitors of Hsp90, phosphatidylinositol 3-kinase, and NOS significantly alleviated this hypoxia-induced attenuation of respiration. Thus we conclude that hypoxia-induced excess NO and its derivatives such as ONOO(-) cause inhibition of the electron transport chain and attenuate O(2) demand, leading to cell survival at extreme hypoxia. More importantly, such an attenuation is found to be independent of HIF-1alpha, which is otherwise thought to be the key regulator of respiration in hypoxia-exposed cells, through a nonphosphorylative glycolytic pathway. The present mechanistic insight will be helpful to understand the difference in the magnitude of endothelial dysfunction.     

模拟高海拔低氧对人体睡眠的影响

在模拟不同海拔高度的低氧条件暴露下,我们记录和测定了6名对象的睡眠生理各项指标。结果如下:在急性低氧暴露下所有对象均出现了睡眠障碍,主要是在夜间规定睡眠时间中觉醒期和觉醒次数增加,深睡眠期和快眼动期减少,睡眠各期的呼吸频率和心率增加。随着低氧暴露时间的延长和多次空气潜水后,各睡眠生理指标有向海平对照值水平发展的趋势。4500m以上的低氧暴露下,所有对象在睡眠中都有周期性呼吸现象出现,并影响体内的缺氧。     

Mitochondrial respiration at low levels of oxygen and cytochrome c

In the intracellular microenvironment of active muscle tissue, high rates of respiration are maintained at near-limiting oxygen concentrations. The respiration of isolated heart mitochondria is a hyperbolic function of oxygen concentration and half-maximal rates were obtained at 0.4 and 0.7 microM O(2) with substrates for the respiratory chain (succinate) and cytochrome c oxidase [N,N,N,N',N'-tetramethyl-p-phenylenediamine dihydrochloride (TMPD)+ascorbate] respectively at 30 degrees C and with maximum ADP stimulation (State 3). The respiratory response of cytochrome c-depleted mitoplasts to external cytochrome c was biphasic with TMPD, but showed a monophasic hyperbolic function with succinate. Half-maximal stimulation of respiration was obtained at 0.4 microM cytochrome c, which was nearly identical to the high-affinity K(')(m) for cytochrome c of cytochrome c oxidase supplied with TMPD. The capacity of cytochrome c oxidase in the presence of TMPD was 2-fold higher than the capacity of the respiratory chain with succinate, measured at environmental normoxic levels. This apparent excess capacity, however, is significantly decreased under physiological intracellular oxygen conditions and declines steeply under hypoxic conditions. Similarly, the excess capacity of cytochrome c oxidase declines with progressive cytochrome c depletion. The flux control coefficient of cytochrome c oxidase, therefore, increases as a function of substrate limitation of oxygen and cytochrome c, which suggests a direct functional role for the apparent excess capacity of cytochrome c oxidase in hypoxia and under conditions of intracellular accumulation of cytochrome c after its release from mitochondria.     

Interaction of the Respiration Control System and Sympathoadrenal System during Adaptation to Intermittent Hypoxia

A study of the functioning of the respiratory system and sympathoadrenal system (SAS) after adaptation to intermittent hypoxia in humans of different ages is described. Considering our own findings and published data, the author discusses the possible mechanisms mediating modifications of the respiratory function and regulating the SAS activity during adaptation to hypoxia. A key role of the carotid glomuses in the modulation of the functional parameters of external respiration and SAS under conditions of hypoxic adaptation is emphasized.