Physiological Responses to Acute Hypobaric and Normobaric Hypoxia: Differences in Maximal Exercise and Clinical Impact.

Currently, launching a satellite into orbit is plausible only for organizations with multi-million dollar budgets and requires three or more years for development and qualification. Small satellites traveling as secondary payloads on regularly scheduled launches provide access to space at a fraction of the cost and in a fraction of the time. However, a modular adaptable satellite container can significantly reduce cost and development schedule. By sealing and pressurizing the container to maintain an earthlike environment in orbit, a payload of unmodified terrestrial electronics can be integrated and launched in a matter of weeks. Such a container, SCUTE (Sealed Container for Universal Terrestrial Equipment), can provide a ride to space for K-12 educational experiments, research projects or electronic sensing and communication equipment. SCUTE can also enable military surveillance missions to be accomplished in a timely manner. A conceptual design investigation for SCUTE has been performed including benchmark designs and preliminary structural, thermal, and pressure loss analyses. This paper presents multiple design concepts for four different SCUTE attributes. The leading concept selected for thermal management is a forced air convection thermal switch (FACTS). Other SCUTE attributes selected for simplicity and compatibility with FACTS are the box configuration, an adjustable payload mounting shelf, and the use of air as the working fluid. These selected concepts are recommended for a preliminary design phase and more detailed analysis to make SCUTE a viable option for rapid and inexpensive access to space.

to the editor: We read a recently published article ([4][1]) with great interest. The authors performed a rigorously controlled study scrutinizing the possible differences in cardiorespiratory responses, control of breathing, and acute mountain sickness (AMS) incidence during short-term (6 h)

To compare hemoglobin mass (Hb(mass)) changes during an 18-d live high-train low (LHTL) altitude training camp in normobaric hypoxia (NH) and hypobaric hypoxia (HH). Twenty-eight well-trained male triathletes were split into three groups (NH: n = 10, HH: n = 11, control [CON]: n = 7) and participated in an 18-d LHTL camp. NH and HH slept at 2250 m, whereas CON slept, and all groups trained at altitudes <1200 m. Hb(mass) was measured in duplicate with the optimized carbon monoxide rebreathing method before (pre-), immediately after (post-) (hypoxic dose: 316 vs 238 h for HH and NH), and at day 13 in HH (230 h, hypoxic dose matched to 18-d NH). Running (3-km run) and cycling (incremental cycling test) performances were measured pre and post. Hb(mass) increased similar in HH (+4.4%, P < 0.001 at day 13; +4.5%, P < 0.001 at day 18) and NH (+4.1%, P < 0.001) compared with CON (+1.9%, P = 0.08). There was a wide variability in individual Hb(mass) responses in HH (-0.1% to +10.6%) and NH (-1.4% to +7.7%). Postrunning time decreased in HH (-3.9%, P < 0.001), NH (-3.3%, P < 0.001), and CON (-2.1%, P = 0.03), whereas cycling performance changed nonsignificantly in HH and NH (+2.4%, P > 0.08) and remained unchanged in CON (+0.2%, P = 0.89). HH and NH evoked similar Hb(mass) increases for the same hypoxic dose and after 18-d LHTL. The wide variability in individual Hb(mass) responses in HH and NH emphasizes the importance of individual Hb(mass) evaluation of altitude training.

Effects of high-altitude exposure on submaximal endurance capacity of men.

Poudel, Sangeeta, Sandesh Gautam, Purushottam Adhikari, and Ken Zafren. Physiological effects of sildenafil versus placebo at high altitude: a systematic review. High Alt Med Biol. 25:16-25, 2024. Introduction: High altitude pulmonary edema (HAPE), a life-threatening condition that affects individuals ascending to high altitude, requires the development of pulmonary hypertension. Sildenafil can be used to prevent and treat HAPE, presumably by decreasing pulmonary artery pressure (PaP). We compared the physiological effects of sildenafil versus placebo at high altitude (above 2,500 m), including the effects on PaP. Methods: We performed a systematic search of PubMed, EMBASE, and Cochrane CENTRAL for randomized controlled studies of the physiological effects of sildenafil in hypoxia in healthy individuals. We conducted a systematic review of all studies meeting our criteria. Results: Of the 14 studies that met the inclusion criteria, 8 were hypobaric hypoxia studies. Six studies reported data at rest at altitudes from 3,650 to 5,245 m. Two were simulations reporting exercise data at equivalent altitudes of 2,750-5,000 m. Nine studies used normobaric hypoxia corresponding to altitudes between 2,500 and 6,400 m. One reported only rest data, two reported rest and exercise data, and the others reported only exercise data. Sildenafil significantly reduced PaP at rest and exercise in hypobaric or normobaric hypoxia. There were no significant differences between arterial oxygen saturation (SpO2) with sildenafil in hypobaric or normobaric hypoxia at rest or exercise. There were no significant differences in heart rate or mean arterial pressure (MAP) at rest or exercise and cardiac output during exercise in hypobaric or normobaric hypoxia. Conclusions: Sildenafil significantly reduces PaP at rest and exercise in normobaric or hypobaric hypoxia. Sildenafil has no significant effects on SpO2, heart rate, cardiac output (during exercise), or MAP at rest or exercise in hypobaric or normobaric hypoxia.

Oxygen delivery to the retinal pigment epithelium and the outer retina is essential for metabolism, function, and survival of photoreceptors. Chronically reduced oxygen supply leads to retinal pathologies in patients and causes age-dependent retinal degeneration in mice. Hypoxia can result from decreased levels of inspired oxygen (normobaric hypoxia) or reduced barometric pressure (hypobaric hypoxia). Since the response of retinal cells to chronic normobaric or hypobaric hypoxia is mostly unknown, we examined the effect of six hypoxic conditions on the retinal transcriptome and photoreceptor morphology. Mice were exposed to short- and long-term normobaric hypoxia at 400 m or hypobaric hypoxia at 3450 m above sea level. Longitudinal studies over 11 weeks in normobaric hypoxia revealed four classes of genes that adapted differentially to the hypoxic condition. Seventeen genes were specifically regulated in hypobaric hypoxia and may affect the structural integrity of the retina, resulting in the shortening of photoreceptor segment length detected in various hypoxic groups. This study shows that retinal cells have the capacity to adapt to long-term hypoxia and that consequences of hypobaric hypoxia differ from those of normobaric hypoxia. Our datasets can be used as references to validate and compare retinal disease models associated with hypoxia.

Muscle mass is reduced during extended exposure to a hypoxic environment. Current research suggests that the physiological response to normobaric and hypobaric hypoxia may be different. It is currently unknown if these previously described differences extend to the skeletal muscle and transcriptional response regulating muscle mass. PURPOSE: To determine the effects of normobaric and hypobaric hypoxia on myogenenic and proteolytic gene expression. METHODS: Recreationally trained subjects (n = 15; age = 24 ± 4 y; VO2max = 3.60 ± 0.83 L · min-1) completed three trials of 60-min cycling at 70% of Wmax followed by 4-h of recovery at ambient control conditions (975 m), normobaric hypoxia (4,420 m), and hypobaric hypoxia (4,420 m). For each trial, a muscle biopsy was taken from the vastus lateralis before exercise and at the end of the 4-h recovery period for analysis of gene expression (RT-qPCR). RESULTS: There were no differences in the myogenic gene expression of MYOD (p = 0.713), MYF-5 (0.053), or MYOG (0.832) between trials. MYF-6 was higher after exercise (p = 0.002) regardless of trial. MSTN decreased from pre- to post-exercise (p < 0.001) in all conditions and was lower in hypobaric hypoxia compared to control condition (p = 0.02) and normobaric condition (p = 0.037). There were no differences in the proteolytic gene expression of atrogin-1 with exercise (p =0.811) or between trials (p = 0.419). However, FOXO3 (p = 0.009) and MuRF-1 (p < 0.001) gene expression increased with exercise but were not different between conditions (p = 0.543, p = 0.327, respectively). CONCLUSION: These data indicate that hypoxic recovery from exercise, regardless of whether normobaric or hypobaric, does not affect the expression of genes related to myogenesis and proteolysis with the exception of a modest attenuation of myostatin in hypobaric hypoxia. Funding provided by the Department of Defense United States Army Medical Research and Materiel Command (DOD USAMRMC: W81XWH-15-2-0075).

Slight differences in physiological responses and nitric oxide (NO) have been reported at rest between hypobaric hypoxia (HH) and normobaric hypoxia (NH) during short exposure.Our study reports NO and oxidative stress at rest and physiological responses during moderate exercise in HH versus NH. Ten subjects were randomly exposed for 24 h to HH (3000 m; FIO2, 20.9%; BP, 530 ± 6 mm Hg) or to NH (FIO2, 14.7%; BP, 720 ± 1 mm Hg). Before and every 8 h during the hypoxic exposures, pulse oxygen saturation (SpO2), HR, and gas exchanges were measured during a 6-min submaximal cycling exercise. At rest, the partial pressure of exhaled NO, blood nitrate and nitrite (NOx), plasma levels of oxidative stress, and pH levels were additionally measured. During exercise, minute ventilation was lower in HH compared with NH (-13% after 8 h, P < 0.05). End-tidal CO2 pressure was lower (P < 0.01) than PRE both in HH and NH but decreased less in HH than that in NH (-25% vs. -37%, P < 0.05).At rest, exhaled NO and NOx decreased in HH (-46% and -36% after 24 h, respectively, P < 0.05) whereas stable in NH. By contrast, oxidative stress was higher in HH than that in NH after 24 h (P < 0.05). The plasma pH level was stable in HH but increased in NH (P < 0.01). When compared with prenormoxic values, SpO2, HR, oxygen consumption, breathing frequency, and end-tidal O2 pressure showed similar changes in HH and NH. Lower ventilatory responses to a similar hypoxic stimulus during rest and exercise in HH versus NH were sustained for 24 h and associated with lower plasma pH level, exaggerated oxidative stress, and impaired NO bioavailability.

Normobaric hypoxia (NH) is used as a surrogate for hypobaric hypoxia (HH). Recent studies reported physiological differences between NH and HH. Baroreflex sensitivity (BRS) decreases at altitude or following intense training. However, until now no study compared the acute and chronic changes of BRS in NH vs. HH. First, BRS was assessed in 13 healthy male subjects prior and after 20h of exposure at 3450m (study 1), and second in 15 well-trained athletes prior and after 18days of "live-high train-low" (LHTL) at 2250m (study 2) in NH vs. HH. BRS decreased (p < 0.05) to the same extent in NH and HH after 20h of hypoxia and after LHTL. These results confirm that altitude decreases BRS but the decrease is similar between HH and NH. The persistence of this decrease after the cessation of a chronic exposure is new and does not differ between HH and NH. The previously reported physiological differences between NH and HH do not appear strong enough to induce different BRS responses.

Background: The physiological effects of hypoxia may be influenced by how hypoxia is achieved. The purpose of this study was to determine the effects of recovery in hypobaric hypoxia (HH), normobaric hypoxia (NH), and normobaric normoxia (NN) after endurance exercise on gene expression related to mitochondrial biogenesis, myogenesis, and proteolysis. Methods: Fifteen recreationally trained subjects each cycled for 1 hour before recovering for 4 hours in NN (laboratory atmospheric conditions, 975 m), HH (depressurized to simulate 4420 m), and NH (fraction of O2 reduced to simulate 4420 m). Muscle biopsy samples were obtained before exercise and after 4 hours of recovery. Results: Blood oxygenation (SpO2) was lower in HH (76.02 ± 0.58%) than NH (79.45 ± 0.56, p < 0.001), which were both lower than in NN (96.3 ± 0.17, p < 0.001). Heart rate was higher in HH (82 ± 2 bpm) than NH (77 ± 1 bpm, p < 0.001), which were both higher than in NN (67 ± 1 bpm, p < 0.001). Mitochondrial transcription factor A (TFAM) mRNA was lower after NN than HH (p = 0.034) or NH (p = 0.005), but was not different between HH and NH (p = 0.460). Myostatin (MSTN) mRNA decreased from pre- to postexercise (p < 0.001) in all conditions and was lower in HH compared with NH (p = 0.035) and NN (p = 0.017). No other differences were noted in genes related to mitochondrial biogenesis, myogenesis, or proteolysis (p > 0.05). Conclusion:TFAM mRNA is lower with hypoxia exposure, but effected by the type of hypoxia. MSTN gene expression is lower after exposure to HH than NH or NN. These data support previous work and caution the translation of NH data obtained in a NH environment to a HH environment.

Normobaric hypoxia (NH) and hypobaric hypoxia (HH) are both used to train aircraft pilots to recognize symptoms of hypoxia. NH (low oxygen concentration) training is often preferred because it is more cost effective, simpler, and safer than HH. It is unclear, however, whether NH is neurophysiologically equivalent to HH (high altitude). Previous studies have shown that neural oscillations, particularly those in the alpha band (8–12 Hz), are impacted by hypoxia. Attention tasks have been shown to reliably modulate alpha oscillations, although the neurophysiological impacts of hypoxia during cognitive processing remains poorly understood. To address this we investigated induced and evoked power alongside physiological data while participants performed an attention task during control (normobaric normoxia or NN), NH (fraction of inspired oxygen = 12.8%, partial pressure of inspired oxygen = 87.2 mmHg), and HH (3962 m, partial pressure of inspired oxygen = 87.2 mmHg) conditions inside a hypobaric chamber. No significant differences between NH and HH were found in oxygen saturation, end tidal gases, breathing rate, middle cerebral artery velocity and blood pressure. Induced alpha power was significantly decreased in NH and HH when compared to NN. Participants in the HH condition showed significantly increased induced lower-beta power and evoked higher-beta power, compared with the NH and NN conditions, indicating that NH and HH differ in their impact on neurophysiological activity supporting cognition. NH and HH were found not to be neurophysiologically equivalent as electroencephalography was able to differentiate NH from HH.

Providing the body with oxygen is one of the most pressing problems of modern physiology and theoretical medicine, since hypoxia underlies the pathogenesis of most diseases, and an in-depth study of these processes is of great practical importance. For the normal functioning of the mechanisms for maintaining the body’s energy balance, it is necessary to preserve the parameters that characterize the functional abilities of oxygen transport systems. Disruption of this process leads to disruption of oxygen homeostasis and the occurrence of hypoxia, i.e. to a discrepancy between O2 delivery and the metabolic demand of an organ or cell. The main universal indicator of oxygen homeostasis, reflecting the adequacy of oxygen delivery and consumption, is the oxygen tension in the blood (PaO2). During hypoxia, PO2 changes either due to a decrease in barometric pressure (hypobaric hypoxia -HH), or due to a decrease in the O2 fraction in the inspired air under normal atmospheric pressure conditions (760 mmHg) (normobaric hypoxia -NН). It has been established that in both hypobaric and normobaric hypoxia, the observed changes in functional indicators are a consequence of a decrease in the partial pressure of oxygen in the environment (PO2).

Providing the body with oxygen is one of the most pressing problems of modern physiology and theoretical medicine, since hypoxia underlies the pathogenesis of most diseases, and an in-depth study of these processes is of great practical importance. For the normal functioning of the mechanisms for maintaining the body’s energy balance, it is necessary to preserve the parameters that characterize the functional abilities of oxygen transport systems. Disruption of this process leads to disruption of oxygen homeostasis and the occurrence of hypoxia, i.e. to a discrepancy between O2 delivery and the metabolic demand of an organ or cell. The main universal indicator of oxygen homeostasis, reflecting the adequacy of oxygen delivery and consumption, is the oxygen tension in the blood (PaO2). During hypoxia, PO2 changes either due to a decrease in barometric pressure (hypobaric hypoxia -HH), or due to a decrease in the O2 fraction in the inspired air under normal atmospheric pressure conditions (760 mmHg) (normobaric hypoxia -NН). It has been established that in both hypobaric and normobaric hypoxia, the observed changes in functional indicators are a consequence of a decrease in the partial pressure of oxygen in the environment (PO2).

The presence of differences in physiological response to a lowered inspired Po2 mediated by hypobaric hypoxia (HH) or normobaric hypoxia (NH) is controversial. This review examines the brief, acute, and subacute respiratory, cardiovascular, and subjective symptom response to intermediate and severe hypoxic exposure in NH and HH. Brief exposures lead to similar physiological responses; this is not the case in acute/subacute exposures. Extrapolating data from NH studies to HH in longer exposures is inappropriate as physiological responses to hypoxia seem to be influenced by the prevailing ambient pressure, especially in chronic exposures where acute mountain sickness severity is greater in HH than NH. Explanations for the discrepancy between the two modalities include differences in ventilatory patterns, alveolar gas disequilibrium, and dissimilar acute hypoxic ventilatory responses. Awareness and consideration of these key differences between NH and HH is essential to their proper application to kinesiology, altitude, and aviation medicine.

The purpose of this research was to compare individual hemoglobin mass (Hbmass) changes following a live high-train low (LHTL) altitude training camp under either normobaric hypoxia (NH) or hypobaric hypoxia (HH) conditions in endurance athletes. In a crossover design with a one-year washout, 15 male triathletes randomly performed two 18-day LHTL training camps in either HH or NH. All athletes slept at 2,250 meters and trained at altitudes <1,200 meters. Hbmass was measured in duplicate with the optimized carbon monoxide rebreathing method before (pre) and immediately after (post) each 18-day training camp. Hbmass increased similarly in HH (916-957 g, 4.5 ± 2.2%, P < 0.001) and in NH (918-953 g, 3.8 ± 2.6%, P < 0.001). Hbmass changes did not differ between HH and NH (P = 0.42). There was substantial interindividual variability among subjects to both interventions (i.e., individual responsiveness or the individual variation in the response to an intervention free of technical noise): 0.9% in HH and 1.7% in NH. However, a correlation between intraindividual ΔHbmass changes (%) in HH and in NH (r = 0.52, P = 0.048) was observed. HH and NH evoked similar mean Hbmass increases following LHTL. Among the mean Hbmass changes, there was a notable variation in individual Hbmass response that tended to be reproducible.NEW & NOTEWORTHY This is the first study to compare individual hemoglobin mass (Hbmass) response to normobaric and hypobaric live high-train low using a same-subject crossover design. The main findings indicate that hypobaric and normobaric hypoxia evoked a similar mean increase in Hbmass following 18 days of live high-train low. Notable variability and reproducibility in individual Hbmass responses between athletes was observed, indicating the importance of evaluating individual Hbmass response to altitude training.