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Transcutaneous measurement of PCO2 at high ambient pressure (41 bar).

The accuracy of transcutaneous CO2 monitoring with the Kontron CO2 sensor was studied during compression to 41 bar and subsequent decompression. The PCO2 was stable and accurate during the test of the sensor in the pressure chamber, although an increase of 0.1-0.2 kPa during compression was found. The function of the transcutaneous sensor was tested in rats at 1 bar for the correlation between transcutaneous PCO2 (PtcCO2) and arterial PCO2 (PaCO2). The correlation coefficient between PtcCO2 and PaCO2 in the rat was found to be 0.93. The time difference between the 90% transcutaneous and 90% arterial response time was 4.6 +/- 0.6 min (mean +/- SEM). Finally, the use of the sensor in rats ventilated at constant minute volume during compression to 41 bar was examined. An increase in PtcCO2 of 0.2-0.4 kPa was found. The present results of transcutaneous PCO2 measurements indicate that this method may be useful in hyperbaric research and treatment.

Animals↗

Effect of nitrogen narcosis on cortical and subcortical evoked responses in the cat.

Four cats were chronically implanted with gross, monopolar electrodes in the lateral geniculate nucleus (LGN), pretectum-superior colliculus (P-SC), primary visual cortex (VI), and secondary visual cortex (VII). Following recovery and preliminary testing, the animals were dived in a dry hyperbaric chamber to the sea water equivalent of 103 m (i.e. 340 ft.) where visual evoked responses were recorded. No decrements in the amplitude of the visual evoked response were found at the LGN, but significant decreases did occur at the other three sites. These data suggested: 1) that the effects of nitrogen narcosis on the visual system are primarily central, and not simply peripheral in nature; 2) that these effects are not limited to the visual cortical mantle; and 3) that the narcosis apparently influences structures involving different anatomical levels of the brain which presumably mediate various types of visual processes. The findings were discussed as they relate to current ideas concerning the underlying neurological causes and behavioral effects of nitrogen narcosis.

Animals↗

[Characteristics of human external respiration under excess intrapulmonary pressure under sea level and "altitude" conditions according to pneumotachographic data].

In 54 pressure chamber experiments 12 healthy male test subjects took part. Their pneumotachograms and other physiological parameters at a positive pressure breathing of 30 mm Hg at sea level and of 125--130 mm Hg at an altitude of 25,000 m at rest and while exercising were recorded. High altitude facilities and pneumotachograph were modified to meet the experimental requirements. The changes in pneumotachographic readings depended on the excess intrapulmonary pressure, its variations with respect to the respiratory stages, efficiency of the external counterpressure on the body, as well as motor activity of the test subjects. The pneumotachographic procedure allows qualitative and quantitative evaluations of external respiration upon excess intrapulmonary pressure, and study of the mechanism of these changes supported by other physiological methods.

Adult↗

A versatile chamber for microphysiologic studies with gas mixtures under high pressure.

A pressure chamber, designed for microelectrode recordings in isolated tissues or organs an capable of withstanding pressures up to 200 bar, is described. The versatility of the vessel allows a wide variety of experimental configurations and several types of studies. It features a complete access, easy visibility, interchangeable tissue bath and micromanipulator modules, as continuous perfusion and temperature control of the preparation under pressure. The ability to move micropipettes in 1-micron steps allows single unit recording on a variety of in vitro preparations at normal or elevated gas pressures. Successful physiologic tests, using the hippocampal slice preparation, are described. The results testify to the reliability of the system and to the usefulness of this in vitro model to study the gas pressure effects on isolated networks of mammalian CNS.

Air Pressure↗

[Effects of simulated flight hypobaric hypoxia and oxygen inhalation on free radical metabolism in various organs of mice].

Objective. To investigate the effects of two types of simulated flight conditions (hypobaric hypoxia and hypobaric oxygen inhalation) on free radical metabolism in various organs of mice. Method. Sixty male Kunming mice were randomly divided into six groups (n=10 each). The experiment comprises two parts. The first part included three groups: normal controls (A1), 1500 m hypobaric hypoxia for 4 wk (B1) and 8 wk (C1). The second part included another three groups: normal control (A2), 5500 m hypobaric oxygen inhalation for 4 wk (B2) and 8 wk (C2). The exposure time in hypobaric chamber was 2 h/d, 3 d/wk. After experiment, caudal blood was taken for routine examination. The mice were decapitated on the next day and brain, heart, lung, liver and kidney homogenates were prepared for measuring malondialdehyde (MDA) content and superoxide dismutase (SOD) activity. Result. Lipid peroxides in lung was significantly increased in C1 group, and the content of myocardial MDA and myocardial SOD activities in C2 group were markedly higher than those in A2 group. There were no significant differences among body weights, mean corpuscular indices and hemoglobin content in the normal control, hypobaric hypoxia and hypobaric oxygen inhalation groups. It demonstrates that repeated mild hypobaric hypoxia for 8 wk causes free radical damage of lung and repeated exposure to 5500 m hypobaric oxygen inhalation for 8 wk may lead to myocardial peroxidative injury in mice. Conclusion. Simulated flight hypobaric hypoxia and oxygen inhalation may lead to free radicals damage of lung and myocardial peroxidative injury in mice.

Altitude↗

Effects of hyperbarism on central respiratory drive and respiratory pattern in humans.

The aim of our study was to evaluate the effects of increasing pressure (from 1 to 3 and 6 atm abs) on respiratory drive, respiratory pattern, and inspiratory impedance of the respiratory system. Seven healthy volunteers were studied during a dry compression to 6 atm abs in a hyperbaric multiplace chamber. We observed a significant increase in tidal volume, P0.1 (the pressure generated in the airway after 100 ms of inspiration against a closed inspiratory line), Ttot, and Ti, and a significant respiratory rate reduction with increasing pressure from 1 to 3 atm.abs; P0.1 also increased significantly when comparing 3 and 6 atm abs measurement with 1 atm abs. The P > 0.01 and P0.1/(VT/Ti) showed a significant progressive increase compared with 1 atm abs. In conclusion, the passage from 1 to 3 and 6 atm abs causes, in healthy subjects at rest, an increase in the central respiratory drive activity, evaluated with P0.1 measurement. The response to the respiration system is an increase in tidal volume and Ti with a decrease in respiratory rate.

Adult↗

Norepinephrine attenuates hypoxia-inhibited thyrotropin-releasing hormone release in median eminence and paraventricular nucleus of rat hypothalamus.

OBJECTIVE: We have previously found that chronic hypoxia inhibited thyrotropin-releasing hormone (TRH) mRNA expression in rat paraventricular nucleus (PVN). This study presented the effects of hypoxia on TRH secretion in rat hypothalamus, and the norepinephrine (NE) involvement in the modulation of TRH secretion during acute hypoxia exposure. SETTING AND DESIGN: Hypoxia was simulated at altitudes of 5 km (10.8% O2) or 7 km (8.2% O2) in a ventilated hypobaric chamber, and control group was set at local altitude of 2.3 km (15.8% O2). The duration of hypoxia exposure was designed acutely and chronically for 0.5, 2, 24 h, 5, 10, and 30 d, respectively. TRH levels were measured by specific radioimmunoassay. RESULTS: The results showed that hypoxia of 5 km or 7 km significantly enhanced TRH levels of the ME and PVN, and reduced serum T3 levels in most hypoxia-exposed groups. Intraventricular injection (icv) of NE (4 nmol/L) induced a decrease in TRH levels in the median eminence (ME) and PVN, and an increased serum T3 levels following hypoxia of 7 km exposure for 2 h, compared with icv saline control, indicating TRH release increased. The stimulating effect of NE on the TRH secretion was abolished by icv antagonist of adrenergic alpha2-receptor, yohimbine (40 nmol/L). CONCLUSIONS: We conclude that acute and chronic hypoxia exposure produces an inhibition of hypothalamic TRH secretion from the ME and PVN. Central adrenergic system may play a stimulating role through alpha2-receptor in the acute hypoxia-modulating TRH release from rat hypothalamus.

Adrenergic alpha-Agonists↗

Enhanced erythropoietin production during hypobaric hypoxia in mice under treatments to keep the erythrocyte mass from rising: implications for the adaptive role of polycythemia.

Stress erythropoiesis is usually considered as a compensatory effort to counteract tissue hypoxia. Its homeostatic importance in anemic hypoxia has not been questioned, but researchers, clinicians, and mountain climbers have had second thoughts on polycythemia as to its appropriateness for hypoxic or altitude hypoxia (HA). Therefore, polycythemia, one of the responses to HA seen in nongenetically adapted mammals, could or could not be considered beneficial. The present study was thus performed to obtain further information on the importance of HA polycythemia on acclimation of mice to HA. To this end, the development of polycythemia was prevented by experimental manipulations (administration of 20 mg/kg/d of the hemolytic drug phenylhydrazine or removal of 0.225 mL/d of blood), and the degree of tissue hypoxia was evaluated from plasma erythropoietin (pEPO) concentration, as determined by immunoassay, in adult female mice exposed to air maintained at 506 mbar (380 mmHg) in a simulated HA (SHA) chamber during at least 23.5 h/d for 9 d. Plasma EPO concentration in those treated hypoxic mice whose hematocrit values remained almost unchanged was between 5.55 and 7.89 times higher (depending on the experimental designs) than in control hypoxic mice allowed to develop HA polycythemia. These results, plus the finding of an inverse relationship between the hematocrit value and pEPO concentration in both the polycythemic and normocythemic SHA-exposed mice indicate that HA polycythemia is highly effective in ameliorating tissue hypoxia under SHA conditions, thus giving support to the concept of the important role of the increased hemoglobin mass in nongenetically adapted animals, whereas a left-shifted oxyhemoglobin dissociation curve confers a good degree of adaptation to HA in genetically adapted animals.

Altitude Sickness↗

Renin, aldosterone, electrolyte, and cortisol responses to hypoxic decompression.

Responses of plasma renin activity, plasma aldosterone, plasma cortisol, and plasma electrolyte concentration and urinary electrolyte and aldosterone excretion were studied in four men during hypoxic decompression to a stimulated altitude of 4,760 m in a pressure chamber. Three of the four subjects developed significant acute mountain sickness. Plasma sodium and potassium concentrations were unchanged. No significant change in plasma renin activity was observed, but values tended to fall. Plasma aldosterone concentration was depressed while plasma cortisol was elevated and diurnal variation lost. Urinary sodium excretion was unchanged, but urinary potassium and aldosterone excretion were decreased. The decrease in plasma and urinary aldosterone and urinary potassium in the absence of change in plasma renin activity or plasma potassium is of uncertain origin. It is unlikely to be due to a decrease in adrenocorticotropin secretion since plasma cortisol rose during the same time. None of the changes could be causally implicated in the development of acute mountain sickness although the increase in plasma cortisol was greatest in the most ill.

Adult↗

Tissue factor is associated with the nonbacterial thrombotic endocarditis induced by a hypobaric hypoxic environment in rats.

High-altitude hypoxia causes a hypercoagulable state. In our previous study on the blood coagulation system in rats, nonbacterial thrombotic endocarditis (NBTE) developed after 4-12 weeks' exposure to the equivalent of 5500 m in altitude. We hypothesized that TF (tissue factor)-producing cells in the cardiac valves might be induced by the hypobaric hypoxic environment (HHE) and then trigger NBTE. A total of 170 male Wistar rats were housed in a chamber at the equivalent of 5500 m altitude for 1-12 weeks. We measured TF activity in the plasma and studied morphological changes in the mitral valves using immunohistochemical and immunoelectrical methods for TF protein and in situ hybridization for TF mRNA. After 4 weeks or more of exposure to HHE, 28 of the 56 surviving rats had developed NBTE. After 4-8 weeks' exposure to HHE, the plasma TF activity level was significantly higher than in control rats. There was a significant correlation between plasma TF activity and the incidence of NBTE. After 1 weeks' exposure to HHE, immunoreactivity for TF protein was detected in foamy macrophages and stromal cells in the cardiac valves. In rats with NBTE, TF protein was present in foamy macrophages and spindle stromal cells and focally present in the extracellular matrix. TF mRNA was detected in some foamy macrophages within the thrombus, TF protein was localized to the rough endoplasmic reticulum and plasma membrane of many macrophages, some fibroblasts, and a few endocardial cells. TF is associated with the pathogenesis of the NBTE induced by exposure to HHE. The accumulation of TF-producing macrophages during exposure to HHE may be responsible for initiating thrombus formation.

Animals↗

Hypobaric-hypoxia-induced pulmonary damage in rats ameliorated by antioxidant erdosteine.

Free radical-mediated injury to lung and pulmonary vasculature is an important mechanism in hypoxia-induced lung damage. In this study, we aimed to investigate the potential protective effects of erdosteine as an antioxidant agent on hypobaric hypoxia-induced pulmonary hypertension. Adult male rats were assigned randomly to three groups. The first group of rats was exposed to hypobaric-hypoxia and the second group was treated with erdosteine (20mg/kg, daily) for 2 weeks, during which time they were in a hypoxic chamber. These groups were compared with normoxic controls. All rats were sacrificed after 2 weeks. The hypoxia-induced increase in right ventricle to left ventricle plus septum weight ratio (from 0.20+/-0.01 to 0.26+/-0.01) was reduced significantly in the erdosteine-treated group (0.23+/-0.01). Malondialdehyde levels were elevated (from 0.33+/-0.11 to 0.59+/-0.02) and total antioxidant status was not changed significantly (from 1.77+/-0.42 to 2.61+/-0.23) by hypoxia. In contrast to the hypoxia-exposed group, malondialdehyde levels were significantly decreased in the erdosteine-treated group (0.37+/-0.02). Total antioxidant status (4.03+/-0.22) was significantly higher in erdosteine-treated rats when compared to non-treated rats. Histopathological examination demonstrated that erdosteine prevented inflammation and protected lung parenchyma and pulmonary endothelium of hypoxia-exposed rats.

Animals↗

Change in strategy of solving psychological tests: evidence of nitrogen narcosis in shallow air-diving.

The depths from 10 to 30 m are usually not considered narcotic in scuba air-diving, and evidence of psychomotor disturbances attributable to nitrogen narcosis at these depths is weak and contradictory. 15 experienced male divers were tested in a chamber at 1, 2, 3, and 4 bars over five consecutive days using a battery of computer generated psychological tests-Computerized Reactionmeter Drenovac (CRD-series). Total test solving time, minimal single task solving time, total "ballast" time, and total number of errors were recorded. Nitrogen narcosis effects were evident at all hyperbaric pressures with marked performance differences among subjects. MANOVA revealed significant effects of nitrogen partial pressure for groups of the same variables as follows: total test solving time (p < 0.001), total "ballast" time (p < 0.001), and total number of errors (p = 0.038), but not for minimal single task solving time. ANOVA showed significant effects of pressure only on tests of visual discrimination of signal location (total test solving time: p = 0.012, total "ballast" time: p < 0.001), simple convergent visual orientation (total test solving time: p = 0.012), and convergent thinking (total test solving time: p = 0.002, total number of errors: p = 0.049). The order of the pressure exposures had no influence on subject performance. Impaired psychomotor processing found during air exposures from 2 to 4 bars suggests that nitrogen narcosis at depths usually considered safe from its effects might be a problem in underwater operations that require accuracy, speed, limited time of performance, and complex psychomotor skills.

Adult↗

Changes in atrial natriuretic peptide and brain natriuretic peptide associated with hypobaric hypoxia-induced pulmonary hypertension in rats.

Experimental pulmonary hypertension induced in a hypobaric hypoxic environment (HHE) is characterized by structural remodeling of the heart and pulmonary arteries. Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) both have diuretic, natriuretic, and hypotensive effects, and both are involved in cardiovascular homeostasis as cardiac hormones. To study the effects of HHE on the natriuretic peptide synthesis system, 170 male Wistar rats were housed in a chamber at the equivalent of the 5500-m altitude level for 1-12 weeks. After 1 week of HHE, pulmonary arterial pressure was significantly raised, and the ratio of left ventricle plus septum over right ventricle of the heart showed a significant decrease (compared with those of ground-level control rats). In both ventricular tissues, the expression of ANP messenger (m)RNA and BNP mRNA increased after exposure to HHE. The amounts of ANP and BNP had decreased significantly in right atrial tissue at 12 weeks of HHE (compared with those of the controls), whereas in ventricular tissues at the same time point, both levels had increased significantly. In in situ hybridization and immunohistochemical studies, the staining of the mRNAs for ANP and BNP and of ANP and BNP themselves was more intense in both ventricular tissues after exposure to HHE than before (i.e., in the controls). The results suggest that, in response to HHE, the changes in ventricular synthesis are similar for ANP and BNP. These changes may play a role in modulating pulmonary hypertension in HHE. However, under our conditions, pulmonary hypertension increased progressively throughout the HHE period.

Altitude Sickness↗

Effect of high pressure on metabolic response to cold in rats.

The ability of rats to regulate body temperature in a cool helium-oxygen (heliox) atmosphere at high pressure was studied. Thermoregulatory ability in seven awake rats was assessed in a pressure chamber at 1.5, 21 and 41 ATA by monitoring body temperature and oxygen consumption during a gradual reduction of ambient temperature. Body temperature was measured by a radiotelemetry transmitter implanted into the intraperitoneal cavity. The thermal conductance of the rats increased from 0.37 to 0.75 W kg-1 degrees C-1 as air was substituted by heliox and increased further to 1.47 and 1.81 W kg-1 degrees C-1 as the pressure was increased to 21 and 41 ATA, respectively. At high pressure the rats were able to maintain body temperature until the metabolic rate reached a value of 21.9 +/- 2.0 W kg-1, which corresponds to peak metabolic rate. This occurred at an ambient temperature of approximately 21 degrees C. Below this ambient temperature the rats did not manage to maintain body temperature. The results show that the thermal effector mechanisms of rats respond adequately to a slowly decreasing ambient temperature in hyperbaric heliox environments.

Animals↗

Acclimation to intermittent hypobaric hypoxia modifies responses to cold at sea level.

INTRODUCTION: Residence at high altitude modifies thremoregulatory responses to cold stress upon return to lower altitude. These changes are difficult to explain since several stresses related to high altitude may interact, including hypoxia, cold, solar radiation, and physical exertion. We hypothesized that adaptation to hypoxia without cold exposure would produce at least part of the observed changes. METHODS: Five men underwent acclimation to intermittent hypoxia (AIH) in a hypobaric chamber (8 h daily for 4 d, and 6 h on the last day, 4500 to 6000 m) at 24 degrees C. Cold stress responses were tested during a whole-body standard cold air test (1 degrees C, 2 h at rest at sea level) both before and after AIH. RESULTS: Increased reticulocyte counts and percentages confirmed acclimation to hypoxia after AIH. Changes in thermoregulation during the cold test included lower mean skin temperature after 60-80 min (18.8 +/- 0.7 degrees C vs. 19.4 +/- 0.7 degrees C); higher mean metabolic heat production (127 +/- 8 W x m(-2) vs. 118 +/- 6 W x m(-2)); and lower heat debt (7.7 +/- 1.3 kJ x kg(-1) vs. 10.3 +/- 1.2 kJ x kg(-1)), without significant change in rectal temperature. Time to onset for continuous shivering decreased after AIH (12 +/- 5 min vs. 21 +/- 6.3 min), and shivering activity occurred at higher mean skin but not rectal temperatures. CONCLUSION: AIH in comfortable ambient temperature leads to a normothermic-insulative-metabolic general cold adaptation. We conclude that AIH modifies the thermoregulatory responses to cold at sea level without cold exposure leading to a cross-adaptation.

Acclimatization↗

Effect of simulated altitude during sleep on moderate-severity OSA.

OBJECTIVE: These studies were conducted to test the hypothesis that isobaric hypoxia would switch OSA to central sleep apnoea (CSA). METHODS: Five adult men (mean age 54.2 +/- 5.5 years, mean BMI 29.9 +/- 6.7 kg/m(2)) with moderate OSA underwent overnight polysomnography at three altitudes. The highest altitude was simulated in a normobaric hypoxic chamber. RESULTS: The obstructive respiratory disturbance index fell from 25.5 +/- 14.4/h at 60 m to 17.3 +/- 9.2/h at 610 m and 0.5 +/- 0.7/h at 2750 m (P = 0.004 compared with 60 m). The central respiratory disturbance index rose from 0.4 +/- 0.5/h at 60 m to 8.1 +/- 5.8/h at 610 m and 78.8 +/- 29.7/h at 2750 m (P < 0.001 compared with 60 m). Mean sleep SaO(2) fell from 94 +/- 1% at 60 m to 93 +/- 1% at 610 m to 85 +/- 4% at 2750 m (P < 0.001 compared with 60 m). CONCLUSION: Moderate severity OSA at sea level (60 m) was completely replaced by severe CSA at a simulated altitude of 2750 m. The authors believe that the OSA resolved because of an increased respiratory drive [corrected] and an increase in upper airway tone, whereas CSA developed because of hypocapnia in non-rapid eye movement sleep.

Analysis of Variance↗

Effects of increased O2-N2 pressure and breathing apparatus on respiratory function.

The ventilatory response of four subjects was measured at rest and various intensities of exercise. Experiments were conducted in a dry pressure chamber (1) at 1 ATA and 4 ATA with the subjects breathing from a low-resistance mouthpiece, and (2) at ATA with the subjects breathing from open-circuit breathing apparatus (Royal Naval Swimmers' Air Breathing Apparatus). At 4 ATA there was significant hypoventilation and hypercapnia, together with an increased tidal volume and lower respiratory frequency. The use of the breathing apparatus tended to amplify these changes in ventilatory response. In addition, the extent of hypercapnia at 4 ATA was related to the exercise intensity. When subjects breathed from a low-resistance mouthpiece, oxygen uptake was significantly greater at 4 ATA than at the surface for the same ergometric work load, but when they breathed from the breathing apparatus, the increase in oxygen uptake was not significant in comparison to surface values. At 4 ATA bradycardia was evident at all levels of exercise but was not affected significantly by the presence of the breathing apparatus.

Atmosphere Exposure Chambers↗

Carbon dioxide exchange of lettuce plants under hypobaric conditions.

Growth of plants in a Controlled Ecological Life Support System (CELSS) may involve the use of hypobaric pressures enabling lower mass requirements for atmospheres and possible enhancement of crop productivity. A controlled environment plant growth chamber with hypobaric capability designed and built at Ames Research Center was used to determine if reduced pressures influence the rates of photosynthesis (Ps) and dark respiration (DR) of hydroponically grown lettuce plants. The chamber, referred to as a plant volatiles chamber (PVC), has a growing area of about 0.2 m2, a total gas volume of about 0.7 m3, and a leak rate at 50 kPa of <0.1%/day. When the pressure in the chamber was reduced from ambient to 51 kPa, the rate of net Ps increased by 25% and the rate of DR decreased by 40%. The rate of Ps increased linearly with decreasing pressure. There was a greater effect of reduced pressure at 41 Pa CO2 than at 81 Pa CO2. This is consistent with reports showing greater inhibition of photorespiration (Pr) in reduced O2 at low CO2 concentrations. When the partial pressure of O2 was held constant but the total pressure was varied between 51 and 101 kPa, the rate of CO2 uptake was nearly constant, suggesting that low pressure enhancement of Ps may be mainly attributable to lowered partial pressure of O2 and the accompanying reduction in Pr. The effects of lowered partial pressure of O2 on Ps and DR could result in substantial increases in the rates of biomass production, enabling rapid throughput of crops or allowing flexibility in the use of mass and energy resources for a CELSS.

Atmosphere Exposure Chambers↗