Search

The ability to respond rapidly to changes in oxygen tension is critical for many forms of life. Challenges to oxygen homeostasis, specifically in the contexts of evolutionary biology and biomedicine, provide important insights into mechanisms of hypoxia adaptation and tolerance. Here we synthesize findings across varying time domains of hypoxia in terms of oxygen delivery, ranging from early animal to modern human evolution and examine the potential impacts of environmental and clinical challenges through emerging multi-omics approaches. We discuss how diverse animal species have adapted to hypoxic environments, how humans vary in their responses to hypoxia (i.e., in the context of high-altitude exposure, cardiopulmonary disease, and sleep apnea), and how findings from each of these fields inform the other and lead to promising new directions in basic and clinical hypoxia research.

Abstract I have been fortunate to work in two areas of extreme physiology and medicine: very high altitude and the microgravity of spaceflight. My introduction to high altitude medicine was as a member of Sir Edmund Hillary's Silver Hut Expedition in 1960–1961 when a small group of physiologists spent the winter and spring at an altitude of 5,800 m just south of Mt. Everest. The physiological objective was to obtain a better understanding of the acclimatization process of lowlanders during exposure to a very high altitude for several months. As far as we knew, no one had ever spent so long at such a high altitude before. The success of this expedition prompted me to organize the 1981 American Medical Research Expedition to Everest where the scientific objective was to determine the physiological changes that allow humans to survive in the extreme hypoxia of the highest point on earth. There is good evidence that this altitude is very near the limit of human tolerance to oxygen deprivation. Much novel information was obtained including an extraordinary degree of hyperventilation which reduced the alveolar partial pressure of carbon dioxide (Pco2) to about 8 mmHg (1.1 kPa) on the summit, and this in turn allowed the alveolar partial pressure of oxygen, PO2, to be maintained at a viable level of about 35 mmHg (4.7 kPa). The low Pco2 caused a severe degree of respiratory alkalosis with an arterial pH exceeding 7.7. These were the first physiological measurements to be made on the Everest summit, and essentially, none has been made since. The second extreme environment is microgravity. We carried out an extensive series of measurements on astronauts in the orbiting laboratory known as SpaceLab in the 1990s. Many aspects of pulmonary function are affected by gravity, so it was not surprising that many changes were found. However, overall gas exchange remained efficient. Some of the findings such as an anomalous behavior of inhaled helium and sulfur hexafluoride have still not been explained. Measurements made after astronauts were exposed to 6 months of microgravity in the International Space Station indicate that the function of the lung returns to its preexposure state within a few days.

Venous gas bubbles occur in recreational SCUBA divers in the absence of decompression sickness, forming venous gas emboli (VGE) which are trapped within pulmonary circulation and cleared by the lung without overt pathology. We hypothesized that asymptomatic VGE would transiently increase ventilation-perfusion mismatch due to their occlusive effects within the pulmonary circulation. Two sets of healthy volunteers (n = 11, n = 12) were recruited to test this hypothesis with a single recreational ocean dive or a baro-equivalent dry hyperbaric dive. Pulmonary studies (intrabreath V A/Q (iV/Q), alveolar dead space, and FVC) were conducted at baseline and repeat 1- and 24-h after the exposure. Contrary to our hypothesis V A/Q mismatch was decreased 1-h post-SCUBA dive (iV/Q slope 0.023 ± 0.008 ml−1 at baseline vs. 0.010 ± 0.005 NS), and was significantly reduced 24-h post-SCUBA dive (0.000 ± 0.005, p

BackgroundClimbers on the summit of Mt. Everest are exposed to extreme hypoxia, and the physiological implications are of great interest. Inferences have been made from alveolar gas samples collected on the summit, but arterial blood samples would give critical information. We propose a plan to insert an arterial catheter at an altitude of 8000 m, take blood samples above this using an automatic sampler, store the samples in glass syringes in an ice-water slurry, and analyze them lower on the mountain 4 to 6 hours later.ResultsA preliminary design of the automatic sampler was successfully tested at the White Mountain Research Station (altitude 3800 m-4300 m). To determine how much the blood gases changed over a long period, rabbit blood was tonometered to give a gas composition close to that expected on the summit (PO2 4.0 kPa (30 mmHg), PCO2 1.3 kPa (10 mmHg), pH 7.7) and the blood gases were measured every 2 hours for 8 hours both at sea level and 3800 m. The mean changes were PO2 +0.3 to +0.4 kPa (+2 to +3 mmHg), PCO2 0 to +0.13 kPa (+1 mmHg), pH -0.02 to +0.04, base excess -0.7 to +1.2 mM. In practice the delay before analysis should not exceed 4 to 6 hours. The small paradoxical rise in PO2 is presumably caused mainly by contamination of the blood with air.ConclusionWe conclude that automatic arterial blood sampling at high altitude is technically feasible and that the changes in the blood gases over a period of several hours are acceptably small.

Compare and contrast strategies remain common pedagogical practices within physiological education. With the support of an American Physiological Society Teaching Career Enhancement Award, we have developed a junior- or senior-level undergraduate curriculum for exercise physiology that compares and contrasts the physiological adaptations of chronic terrestrial exercise (TEx) and microgravity ([mu]G). We used a series of peer-reviewed publications to demonstrate that many of the physiological adaptations to TEx and [mu]G are opposite. For example, TEx typically improves cardiovascular function and orthostatic tolerance, whereas [mu]G can lead to declines in both. TEx leads to muscle hypertrophy, and [mu]G elicits muscle atrophy. TEx increases bone mineral density and red blood cell mass, whereas [mu]G decreases bone mineral density and red blood cell mass. Importantly, exercise during spaceflight remains a crucial countermeasure to limit some of these adverse physiological adaptations to [mu]G. This curriculum develops critical thinking skills by dissecting peer-reviewed articles and discussing the strengths and weaknesses associated with simulated and actual [mu]G studies. Moreover, the curriculum includes studies on both animals and humans, providing a strong translational component to the curriculum. In summary, we have developed a novel space physiology curriculum delivered during the final weeks of an exercise physiology course in which students gain critical new knowledge that reinforces key concepts presented throughout the semester.