Effect of increased gas density on pulmonary gas exchange in man.

Pulmonary gas exchange was measured in seven resting supine subjects breathing air or a dense gas mixture containing 21% O2 in sulfur hexafluoride (SF6). The mean value of the alveolar-arterial oxygen difference (AaDO2) decreased from 12.4 on air to 7.0 on SF6 (P less than 0.01), and increased again to 13.4 when air breathing resumed (P less than 0.01). No differences occurred between gas mixtures for O2 consumption, respiratory quotient, minute ventilation, breathing frequency, heart rate, or blood pressure, and the improved oxygen transfer could not be attributed to changes in cardiac output or mixed venous oxygen content in the one subject in which they were measured. These results are best explained by an altered distribution of ventilation during dense gas breathing, so that the ventilation-perfusion ratio (VA/Q) variance was reduced. Of several considered mechanisms, we favor one in which SF6 promotes cardiogenic gas mixing between peripheral parallel units having different alveolar gas concentrations. This mechanism allows for observed increases in arterial carbon dioxide tension and dead space-to-tidal volume ratio during dense gas breathing, and suggests that intraregional VA/Q variance accounts for at least one-half of the resting AaDO2 in healthy supine young men.     

Radiation protection of mice with hypoxic gas mixtures after administration of anti-hypoxic agents

It is shown that such substances as gutimine, antizol and mexamine increases the resistance of animals to short-term breathing of gas mixtures containing 6 and 5% oxygen. Even if some of them decrease the degree of radioprotective effect of hypoxia, they afford the possibility to safe use of breathing mixtures with lower oxygen content than endured by intact animals, with the resulting increase in radioprotection. Thus the antihypoxic substances can be tested during hypoxiradiotherapy of human tumors.     

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.     

Work of Breathing into Snow in the Presence versus Absence of an Artificial Air Pocket Affects Hypoxia and Hypercapnia of a Victim Covered with Avalanche Snow: A Randomized Double Blind Crossover Study

Presence of an air pocket and its size play an important role in survival of victims buried in the avalanche snow. Even small air pockets facilitate breathing. We hypothesize that the size of the air pocket significantly affects the airflow resistance and work of breathing. The aims of the study are (1) to investigate the effect of the presence of an air pocket on gas exchange and work of breathing in subjects breathing into the simulated avalanche snow and (2) to test whether it is possible to breathe with no air pocket. The prospective interventional double-blinded study involved 12 male volunteers, from which 10 completed the whole protocol. Each volunteer underwent two phases of the experiment in a random order: phase “AP”—breathing into the snow with a one-liter air pocket, and phase “NP”—breathing into the snow with no air pocket. Physiological parameters, fractions of oxygen and carbon dioxide in the airways and work of breathing expressed as pressure-time product were recorded continuously. The main finding of the study is that it is possible to breath in the avalanche snow even with no air pocket (0 L volume), but breathing under this condition is associated with significantly increased work of breathing. The significant differences were initially observed for end-tidal values of the respiratory gases (EtO₂ and EtCO₂) and peripheral oxygen saturation (SpO₂) between AP and NP phases, whereas significant differences in inspiratory fractions occurred much later (for F_IO₂) or never (for F_ICO₂). The limiting factor in no air pocket conditions is excessive increase in work of breathing that induces increase in metabolism accompanied by higher oxygen consumption and carbon dioxide production. The presence of even a small air pocket reduces significantly the work of breathing.     

Fetal oxygen consumption and PO2 during hypercapnia in pregnant sheep

In 12 experiments on 9 chronically-cathetized pregnant sheep (116-143 days of gestation), fetal oxygen consumption, umbilical blood flow and blood gas values were measured before, during and after a 30-min period of hypercapnia, induced by having the ewes breathe 5% CO2 and 18% O2 in N2. During the large amplitude breathing stimulated by hypercapnia, O2 consumption increased by 21%, solely via a rise in O2 extraction. During apnoeic periods and low amplitude breathing in the hypercapnia period, oxygen consumption was not different from the control value, but fetal arterial and umbilical venous PO2 was significantly raised, by 3 and 6 mm Hg respectively. These changes were probably due to a Bohr shift in the maternal oxygen dissociation curve. During large amplitude breathing, PO2 fell to control levels, probably due in part to the increase in O2 extraction. It is concluded that vigorous breathing movements in the fetal sheep, such as those stimulated by hypercapnia, result to an increase in fetal O2 demands. Further, the work of such breathing is large, and probably equivalent to that performed in adults during vigorous hyperventilation against an inspiratory resistance.     

The influence of a respiratory acidosis on the exercise blood lactate response

The purpose of the present study was to examine the influence of a respiratory acidosis on the blood lactate (La) threshold and specific blood La concentrations measured during a progressive incremental exercise test. Seven males performed three step-incremental exercise tests (20 W.min-1) breathing the following gas mixtures; 21% O2 balance-nitrogen, and 21% O2, 4% CO2 balance-nitrogen or balance-helium. The log-log transformation of La oxygen consumption (VO2) relationship and a 1 mmol.l-1 increase above resting values were used to determine a La threshold. Also, the VO2 corresponding to a La value of 2 (La2) and 4 (La4) mmol.l-1 was determined. Breathing the hypercapnic gas mixtures significantly increased the resting partial pressure of carbon dioxide (PCO2) from 5.6 kPa (42 mm Hg) to 6.1 kPa (46 mm Hg) and decreased pH from 7.395 to 7.366. During the incremental exercise test, PCO2 increased significantly to 7.2 kPa (54 mm Hg) and 6.8 kPa (51 mm Hg) for the hypercapnic gas mixtures with nitrogen and helium, respectively, and pH decreased to 7.194 and 7.208. In contrast, blood PCO2 decreased to 4.9 kPa (37 mm Hg) at the end of the normocapnic exercise test and pH decreased to 7.291. A blood La threshold determined from a log-log transformation [1.20 (0.28) l.min-1] or as an increase of 1 mmol.l-1 [1.84 (0.46) l.min-1] was unaffected by the acid-base alterations. Similarly, the VO2 corresponding to La2 and La4 was not affected by breathing the hypercapnic gas mixtures [2.12 (0.46) l.min-1 and 2.81 (0.52) l.min-1, respectively].(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

Serum erythropoietin levels in healthy humans after a short period of normobaric and hyperbaric oxygen breathing: the "normobaric oxygen paradox".

Renal (peritubular) tissue hypoxia is a well-known physiological trigger for erythropoietin (EPO) production. We investigated the effect of rebound relative hypoxia after hyperoxia obtained under normo- and hyperbaric oxygen breathing conditions. A group of 16 healthy volunteers were investigated before and after a period of breathing 100% normobaric oxygen for 2 h and a period of breathing 100% oxygen at 2.5 ATA for 90 min (hyperbaric oxygen). Serum EPO concentration was measured using a radioimmunoassay at various time points during 24-36 h. A 60% increase (P < 0.001) in serum EPO was observed 36 h after normobaric oxygen. In contrast, a 53% decrease in serum EPO was observed at 24 h after hyperbaric oxygen. Those changes were not related to the circadian rhythm of serum EPO of the subjects. These results indicate that a sudden and sustained decrease in tissue oxygen tension, even above hypoxia thresholds (e.g., after a period of normobaric oxygen breathing), may act as a trigger for EPO serum level. This EPO trigger, the "normobaric oxygen paradox," does not appear to be present after hyperbaric oxygen breathing.     

Effect of changes in arterial oxygen content on circulation and physical performance.

To evaluate the effect of different levels of arterial oxygen content on hemodynamic parameters during exercise nine subjects performed submaximal bicycle or treadmill exercise and maximal treadmill exercise under three different experimental conditions: 1) breathing room air (control); 2) breathing 50% oxygen (hyperoxia); 3) after rebreathing a carbon monoxide gas mixture (hypoxia). Maximal oxygen consumption (Vo2 max) was significantly higher in hyperoxia (4.99 1/min) and significantly lower in hypoxia (3.80 1/min) than in the control experiment (4.43 1/min). Physical performance changes in parallel with Vo2 max. Maximal cardiac output (Qmax) was similar in hyperoxia as in control but was significantly lower in hypoxia mainly due to a decreased stroke volume. A correlation was found between Vo2 max and transported oxygen, i.e., Cao2 times Amax, thus suggesting that central circulation is an important limiting factor for human maximal aerobic power. During submaximal work HR was decreased in hyperoxia and increased in hypoxia. Corresponding Q values were unchanged except for a reduction during high submaximal exercise in hyperoxia.     

Electrical activity of the brain and oxygen supply for cognitive-mnestic activity in humans under different degrees of hypoxia

Comparative analysis of the indices of oxygen supply for the body and the brain and the functional state of the brain was carried out in three experimental situations: performance of cognitive-mnestic tests under normoxic (TN) and hypoxic conditions (TH) and exposure to hypoxia in the absence of cognitive tasks (H). Each subject participated in all of the experiments. Hypoxic conditions were created by breathing of a hypoxic gas mixture (HGM) consisting of oxygen and nitrogen for 25 min. The first group (eight subjects) was exposed to moderate hypoxia, with the gas mixture containing 12% O₂ (HGM-12); the second group (eight subjects) was exposed to severe hypoxia, with the gas mixture containing 8% O₂ (HGM-8). The cognitive-mnestic activity (CMA) under both normoxia and hypoxia was continuous and included the following tests: “Arithmetic calculations,” “Memory for numerals,” “Colored figures”, and “Sensorimotor response time.” The CMA efficiency was significantly impaired only under severe hypoxia (HGM-8). The CMA efficiency was higher in some subjects of the first group (HGM-12) in the TH series as compared to that in the TN series. The EEG spectral power (SP) during CMA was decreased as compared to the background in all subjects in the TN series and in most subjects of the first group, exposed to HGM-12, whereas it was increased in all subjects of the second group, exposed to HGM-8. The EEG SP was lower in most subjects of both groups studied in the TH series as compared to that found in the H series. The rheographic index of cerebral blood flow rate was not changed compared to the background in the TN series and was increased in the H and TH series during HGM-8 treatment. The increase in cerebral blood flow was less pronounced in the TH series as compared to the H series in most subjects of the second group (HGM-8). Oxygen consumption by the body was elevated by 10–20% in the TN series. A significant increase in oxygen consumption was found in the subjects of both groups studied during hypoxia treatment (H), and it was greater in HGM-12. The following differences were found between the subjects of the two experimental groups: the increase in oxygen consumption in most subjects of the first group (HGM-12) was higher in the TH series as compared to the H series, whereas, in most subjects of the second group (HGM-8), the increase in oxygen consumption was higher in the H series. The data are discussed from the point of view of synergic and concurrent relationships between different forms of energy expenditure on structural and functional reorganization and organ-specific functions.     

Effect of hypercapnia on thermoregulation at high ambient temperature

The reported investigations were carried out on rabbits exposed for three hours to ambient temperature of 25 degrees C or 35 degrees breathing athmospheric air (controls) or gas mixtures containing 4% or 7% of CO2. During the exposure to 35 degrees C in rabbits breathing the gas mixture with 7% of CO2 the rise of rectal temperature was significantly greater, heat elimination from the auricular surface was increased, whereas the oxygen uptake was increased insignificantly. In tracheostomized rabbits breathing the gas mixture with 7% of CO2 at 32 degrees C the respiratory rate decreased but the respiration volume increased as compared with the animals breathing atmospheric air. It seems that the hyperthermic effect of hypercapnia demonstrated in this work can be attributed to the impairment of heat elimination through the upper airways due to an inhibition of thermal panting.     

Individual characteristics of external respiration during intermittent normobaric hypoxia

Correlation and regression relationships between the indices of the body responsiveness to hypoxic impacts and initial individual values of indices of the respiratory system and heart activity were studied in a group of subjects during three repeated cycles of breathing alternately a hypoxic gas mixture (11 vol % O₂) for 5 min and normal air for 5 min. A steady negative correlation between the most important regulatory indicator, the increase in the CO₂ content of the lungs, and its initial level in individual subjects was found. This may determine the known “normalizing” curative and prophylactic effects of intermittent normobaric hypoxia on the gas transport system of the body. A correlation between the individual increase in the CO₂ content of the lungs in response to hypoxia and changes in the heart rate and initial inhalation rate and depth, rather than oxygen consumption by the body, was found.     

Standardized estimation of external respiration function

External respiration in healthy males has, in addition to eupnea, six functionally active variants with one or several indices deviating from the normal values. Hyperpnea and hypopnea are determined by deviations in general oxygen consumption accompanied by adequate changes in pulmonary ventilation and gas exchange. Inhibition of gas exchange in the respiratory parts of the lungs is a typical primary event of hyperventilation, a fact indicated by a decrease in the coefficient of oxygen consumption and a compensatory increase in the minute respiratory volume during hyperventilation. Tension of the respiratory system is especially pronounced during enhanced oxygen consumption (O₂C). Highly effective bradypnea is characterized by infrequent and deep breathing. No tension of the respiratory system is observed even for increased O₂C. This state may be considered a genotypic and phenotypic variant of normal respiration. The data obtained may be used to automate the assessment of gas exchange in the respiratory parts of the lungs.     

Acute alterations in stroke volume during exercise at 3,100 m altitude.

Following 3 weeks exposure to an altitude of 3,100 m, the cardiac output response to upright submaximal exercise was examined in 3 healthy subjects breathing ambient air and breathing 60% oxygen. The procedure allowed acute alteration of the 2 conditions within a single testing period of 30 min, 60% oxygen breathing either preceding or following breathing ambient air. Cardiac output was also measured in two of the subjects during maximal exercise under these two conditions. Administration of the high oxygen inspirate during exercise had little effect on the level of cardiac output but resulted in an immediate bradycardia and a dramatic increase of approximately 16% in stroke volume. Stroke volumes during maximal exercise were also increased by approximately 10% by the administration of high oxygen. It is suggested that the condition of decreases exercise stroke volume which develops with chronic exposure to altitude may be largely the result of diminished myocardial contractility stemming from a condition of myocardial hypoxia.     

The respiratory system as an exercise limiting factor in normal trained subjects

Recently, we have shown that an untrained respiratory system does limit the endurance of submaximal exercise (64% peak oxygen consumption) in normal sedentary subjects. These subjects were able to increase breathing endurance by almost 300% and cycle endurance by 50% after isolated respiratory training. The aim of the present study was to find out if normal, endurance trained subjects would also benefit from respiratory training. Breathing and cycle endurance as well as maximal oxygen consumption (VO2max) and anaerobic threshold were measured in eight subjects. Subsequently, the subjects trained their respiratory muscles for 4 weeks by breathing 85-160 l.min-1 for 30 min daily. Otherwise they continued their habitual endurance training. After respiratory training, the performance tests made at the beginning of the study were repeated. Respiratory training increased breathing endurance from 6.1 (SD 1.8) min to about 40 min. Cycle endurance at the anaerobic threshold [77 (SD 6) %VO2max] was improved from 22.8 (SD 8.3) min to 31.5 (SD 12.6) min while VO2max and the anaerobic threshold remained essentially the same. Therefore, the endurance of respiratory muscles can be improved remarkably even in trained subjects. Respiratory muscle fatigue induced hyperventilation which limited cycle performance at the anaerobic threshold. After respiratory training, minute ventilation for a given exercise intensity was reduced and cycle performance at the anaerobic threshold was prolonged. These results would indicate the respiratory system to be an exercise limiting factor in normal, endurance trained subjects.     

Response of subjects trained to hold their breath to intermittent normobaric hypoxia

The change in the external respiration parameters was studied in individuals engaging in sports (swimming) combined with training in voluntary cyclic breath holding during a session of intermittent normobaric hypoxia (three cycles of 5 min breathing a gas mixture containing 10.7% O₂ alternating with 5 min breathing ordinary air). It was shown that they differed from the control group in sharp variations in the oxygen consumption rate, which were accompanied by equally marked changes in the effectiveness of oxygen binding in the lungs with a slightly increased stable level of pulmonary ventilation and a bradypneic type of breathing. An increase in the alveolar concentration of carbonic acid and a dramatic increase in the effectiveness of its elimination are significant features of the adaptive process in the mechanism of regulation of external respiration in this training.     

Ventilatory and metabolic responses of burrowing owls, Athene cunicularia, to moderate and extreme hypoxia: analysis of the hypoxic ventilatory threshold vs. hemoglobin oxygen affinity relationship in birds

We measured ventilation, oxygen consumption and blood gases in burrowing owls (Athene cunicularia) breathing moderate and extreme hypoxic gas mixtures to determine their hypoxic ventilatory threshold (HVT) and to assess if they, like other birds and mammals, exhibit a relationship between HVT and hemoglobin O2 affinity (P(50)) of their blood. An earlier report of an attenuated ventilatory responsiveness of this species to hypoxia was enigmatic given the low O2 affinity (high P(50)) of burrowing owl hemoglobin. In the current study, burrowing owls breathing 11% and 9% O2 showed a significantly elevated total ventilation. The arterial partial pressure of oxygen (PaO2) at which ventilation is elevated above normoxic values in burrowing owls was 58 mm Hg. This threshold value conforms well to expectations based on the high P(50) of their hemoglobin and the HVT vs. P(50) relationship for birds developed in this study. Correcting for phylogenetic relatedness in the multi-species analysis had no effect on the HVT vs. P(50) relationship. Also, because burrowing owls in this study did not show a hypometabolic response at any level of hypoxia (even at 9% O2); HVT described in terms of percent change in oxygen convection requirement is identical to that based on ventilation alone.     

Ventilatory and metabolic responses of burrowing owls, Athene cunicularia, to moderate and extreme hypoxia: analysis of the hypoxic ventilatory threshold vs. hemoglobin oxygen affinity relationship in birds.

We measured ventilation, oxygen consumption and blood gases in burrowing owls (Athene cunicularia) breathing moderate and extreme hypoxic gas mixtures to determine their hypoxic ventilatory threshold (HVT) and to assess if they, like other birds and mammals, exhibit a relationship between HVT and hemoglobin O2 affinity (P(50)) of their blood. An earlier report of an attenuated ventilatory responsiveness of this species to hypoxia was enigmatic given the low O2 affinity (high P(50)) of burrowing owl hemoglobin. In the current study, burrowing owls breathing 11% and 9% O2 showed a significantly elevated total ventilation. The arterial partial pressure of oxygen (PaO2) at which ventilation is elevated above normoxic values in burrowing owls was 58 mm Hg. This threshold value conforms well to expectations based on the high P(50) of their hemoglobin and the HVT vs. P(50) relationship for birds developed in this study. Correcting for phylogenetic relatedness in the multi-species analysis had no effect on the HVT vs. P(50) relationship. Also, because burrowing owls in this study did not show a hypometabolic response at any level of hypoxia (even at 9% O2); HVT described in terms of percent change in oxygen convection requirement is identical to that based on ventilation alone.     

Autonomic cardiovascular function in high-altitude Andean natives with chronic mountain sickness.

We evaluated autonomic cardiovascular regulation in subjects with polycythemia and chronic mountain sickness (CMS) and tested the hypothesis that an increase in arterial oxygen saturation has a beneficial effect on arterial baroreflex sensitivity in these subjects. Ten Andean natives with a Hct >65% and 10 natives with a Hct <60%, all living permanently at an altitude of 4,300 m, were included in the study. Cardiovascular autonomic regulation was evaluated by spectral analysis of hemodynamic parameters, while subjects breathed spontaneously or frequency controlled at 0.1 and 0.25 Hz, respectively. The recordings were repeated after a 1-h administration of supplemental oxygen and after frequency-controlled breathing at 6 breaths/min for 1 h, respectively. Subjects with Hct >65% showed an increased incidence of CMS compared with subjects with Hct <60%. Spontaneous baroreflex sensitivity was significantly lower in subjects with high Hct compared with the control group. The effects of supplemental oxygen or modification of the breathing pattern on autonomic function were as follows: 1) heart rate decreased significantly after both maneuvers in both groups, and 2) spontaneous baroreflex sensitivity increased significantly in subjects with high Hct and did not differ from subjects with low Hct. Temporary slow-frequency breathing may provide a beneficial effect on the autonomic cardiovascular function in high-altitude natives with CMS.     

Theoretical and experimental evaluation of the effects of an argon gas mixture on the pressure drop through adult tracheobronchial airway replicas

Argon has the potential to be a novel inhaled therapeutic agent, owing to the neuroprotective and organoprotective properties demonstrated in preclinical studies. Before human trials are performed, an understanding of varying gas properties on airway resistance during inhalation is essential. This study predicts the effect of an 80% argon/20% oxygen gas mixture on the pressure drop through conducting airways, and by extension the airway resistance, and then verifies these predictions experimentally using 3-D printed adult tracheobronchial airway replicas.The predicted pressure drop was calculated using established analytical models of airway resistance, incorporating the change in viscosity and density of the 80% argon/20% oxygen mixture versus that of air. Predicted pressure drop for the argon mixture increased by approximately 29% compared to that for air. The experimental results were consistent with this prediction for inspiratory flows ranging from 15 to 90 slpm. These results indicate that established analytical models may be used to predict increases in conducting airway resistance for argon/oxygen mixtures, compared with air. Such predictions are valuable in predicting average patient response to breathing argon/oxygen mixtures, and in selecting or designing delivery systems for use in administration of argon/oxygen mixtures to critically ill or injured patients.