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Biochemistry, Genetics and Molecular Biology › Genetics

High Altitude and Hypoxia

Works Count: 49314

Description

This cluster of papers explores the genetic and physiological adaptations of humans and other vertebrates to high-altitude environments, focusing on topics such as hypoxia, acute mountain sickness, erythropoietin response, oxidative stress, pulmonary edema, and the effects of endurance training. The research covers a wide range of aspects including molecular, systemic, and cellular responses to high-altitude conditions.

Keywords

High Altitude; Adaptation; Hypoxia; Genetic; Physiological; Acute Mountain Sickness; Erythropoietin; Oxidative Stress; Pulmonary Edema; Endurance Training

Oxidative stress: animal adaptations in nature.

1996-12-01
Kenneth B. Storey
As a consequence of aerobic life, an organism must deal with the continuous generation of reactive oxygen species (O2-, H202, .OH) as byproducts of metabolism and defend itself against the … As a consequence of aerobic life, an organism must deal with the continuous generation of reactive oxygen species (O2-, H202, .OH) as byproducts of metabolism and defend itself against the harm that these can do to cellular macromolecules. Organisms protect themselves from such damage with both enzymatic and nonenzymatic antioxidant defenses. However, the reperfusion injuries noted after ischemic insult in mammalian organs and ascribed to a burst of reactive oxygen species produced when oxygenated blood is reintroduced demonstrate that the antioxidant defenses of many organisms can be overwhelmed, Although unusual among most mammals, many organisms routinely experience wide variation in oxygen availability to their tissues due to factors such as environmental oxygen lack, breath-hold diving, extracellular freezing, or apnoeic breathing patterns in arrested metabolic states. In recent studies using various animal models (anoxia-tolerant turtles, freeze-tolerant snakes and frogs, estivating snails) our laboratory has explored the adaptations of antioxidant defenses that allow such organisms to deal with rapid changes in tissue oxygenation with little or no accumulation of damage products. The key to successful transitions in several systems is the induction, during the oxygen-limited state, of elevated activities of antioxidant and associated enzymes, such as catalase, superoxide dismutase, glutathione-S-transferase, and glutathione peroxidase, so that damage during the reintroduction of oxygen (such as lipid peroxidation) is minimized. However, animals that are excellent facultative anaerobes, such as freshwater turtles, appear to deal with potential of oxidative stress during the anoxic-aerobic transition by maintaining constitutively high antioxidant defenses (e.g. enzyme activities similar to those of mammals and much higher than those of anoxia-intolerant lower vertebrates) that can readily accommodate the burst of reactive oxygen species generation when breathing is renewed.

Peripheral chemoreceptors and cardiovascular regulation

1994-07-01
Janice M. Marshall

Operation Everest II: oxygen transport during exercise at extreme simulated altitude

1988-04-01
J. R. Sutton , John Τ. Reeves , Peter D. Wagner +7 more
A decrease in maximal O2 uptake has been demonstrated with increasing altitude. However, direct measurements of individual links in the O2 transport chain at extreme altitude have not been obtained … A decrease in maximal O2 uptake has been demonstrated with increasing altitude. However, direct measurements of individual links in the O2 transport chain at extreme altitude have not been obtained previously. In this study we examined eight healthy males, aged 21-31 yr, at rest and during steady-state exercise at sea level and the following inspired O2 pressures (PIO2): 80, 63, 49, and 43 Torr, during a 40-day simulated ascent of Mt. Everest. The subjects exercised on a cycle ergometer, and heart rate was recorded by an electrocardiograph; ventilation, O2 uptake, and CO2 output were measured by open circuit. Arterial and mixed venous blood samples were collected from indwelling radial or brachial and pulmonary arterial catheters for analysis of blood gases, O2 saturation and content, and lactate. As PIO2 decreased, maximal O2 uptake decreased from 3.98 ±0.20 l/min at sea level to 1.17 ± 0.08 l/min at PIO2 43 Torr. This was associated with profound hypoxemia and hypocapnia; at 60 W of exercise at PIO2 43 Torr, arterial PO2 = 28 ± 1 Torr and PCO2 = 11 ± 1 Torr, with a marked reduction in mixed venous PO2 [14.8 ± 1 (SE) Torr]. Considering the major factors responsible for transfer of O2 from the atmosphere to the tissues, the most important adaptations occurred in ventilation where a fourfold increase in alveolar ventilation was observed. Diffusion from alveolus to end-capillary blood was unchanged with altitude. The mass circulatory transport of O2 to the tissue capillaries was also unaffected by altitude except at PIO2 43 Torr where cardiac output was increased for a given O2 uptake. Diffusion from the capillary to the tissue mitochondria, reflected by mixed venous PO2, was also increased with altitude. With increasing altitude, blood lactate was progressively reduced at maximal exercise, whereas at any absolute and relative submaximal work load, blood lactate was higher. These findings suggest that although glycogenolysis may be accentuated at low work loads, it may not be maximally activated at exhaustion.

Voluntary strength and fatigue

1954-03-29
P A Merton

EVEREST STUDY

2012-03-16
Adrian Koh , Won Ki Lee , Lee-Jen Chen +7 more
In Brief Purpose: To assess the effects of verteporfin photodynamic therapy (PDT) combined with ranibizumab or alone versus ranibizumab monotherapy in patients with symptomatic macular polypoidal choroidal vasculopathy. Methods: In … In Brief Purpose: To assess the effects of verteporfin photodynamic therapy (PDT) combined with ranibizumab or alone versus ranibizumab monotherapy in patients with symptomatic macular polypoidal choroidal vasculopathy. Methods: In this multicenter, double-masked, primarily indocyanine green angiography–guided trial, 61 Asian patients were randomized to verteporfin PDT (standard fluence), ranibizumab 0.5 mg, or the combination. Patients were administered with verteporfin PDT/placebo and initiated with three consecutive monthly ranibizumab/sham injections starting Day 1, and re-treated (Months 3–5) as per predefined criteria. The primary endpoint was the proportion of patients with indocyanine green angiography–assessed complete regression of polyps at Month 6. Secondary endpoints included mean change in best-corrected visual acuity at Month 6 and safety. Results: At Month 6, verteporfin combined with ranibizumab or alone was superior to ranibizumab monotherapy in achieving complete polyp regression (77.8% and 71.4% vs. 28.6%; P < 0.01); mean change ± standard deviation in best-corrected visual acuity (letters) was 10.9 ± 10.9 (verteporfin PDT + ranibizumab), 7.5 ± 10.6 (verteporfin PDT), and 9.2 ± 12.4 (ranibizumab). There were no new safety findings with either drug used alone or in combination. Conclusion: Verteporfin PDT combined with ranibizumab 0.5 mg or alone was superior to ranibizumab monotherapy in achieving complete regression of polyps in this 6-month study in patients with symptomatic macular polypoidal choroidal vasculopathy. All treatments were well tolerated over 6 months. EVEREST, the first, multicenter, double-masked, primarily indocyanine green angiography–guided randomized controlled trial for symptomatic macular polypoidal choroidal vasculopathy, demonstrated superiority of verteporfin photodynamic therapy combined with ranibizumab or alone over ranibizumab monotherapy in achieving complete regression of polyps at Month 6. Best-corrected visual acuity improved in all treatment arms.

HIGH ALTITUDE INCREASES CIRCULATING INTERLEUKIN-6, INTERLEUKIN-1 RECEPTOR ANTAGONIST AND C-REACTIVE PROTEIN

2000-03-01
Gunther Hartmann , M. Tschöp , R. Fischer +6 more

Regulation of central blood volume and cardiac filling in endurance athletes: the Frank-Starling mechanism as a determinant of orthostatic tolerance.

1993-06-01
B. D. Levine
Orthostatic intolerance may result from either an abnormally large postural decrease in central blood volume, cardiac filling pressures, and stroke volume, or inadequate neurohumoral responses to orthostasis. Endurance athletes have … Orthostatic intolerance may result from either an abnormally large postural decrease in central blood volume, cardiac filling pressures, and stroke volume, or inadequate neurohumoral responses to orthostasis. Endurance athletes have been reported as having a high incidence of orthostatic intolerance, which has been attributed primarily to abnormalities in baroreflex regulation of heart rate and peripheral resistance. In this review, we present evidence that athletes also have structural changes in the cardiovascular system that although beneficial during exercise, lead to an excessively large decrease in stroke volume during orthostasis and contribute to orthostatic intolerance. A unifying hypothesis based on cardiac mechanics that may explain the divergence of findings in conditions such as bed rest or spaceflight, and short- and long-term endurance training is presented.

THE PHYSIOLOGICAL MEANING OF THE MAXIMAL OXYGEN INTAKE TEST1

1958-04-01
Jere H. Mitchell , Brian J. Sproule , Carleton B. Chapman
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Acute Mountain Sickness in a General Tourist Population at Moderate Altitudes

1993-04-15
Benjamin Honigman
Objective: To determine the incidence of acute mountain sickness in a general population of visitors to moderate elevations, the characteristics associated with it, and its effect on physical activity. Design: … Objective: To determine the incidence of acute mountain sickness in a general population of visitors to moderate elevations, the characteristics associated with it, and its effect on physical activity. Design: A cross-sectional study. Setting: Resort communities located at 6300 to 9700 feet elevation in the Rocky Mountains of Colorado. Participants: Convenience sample of 3158 adult travelers, 16 to 87 years old (mean age [SD], 43.8 11.8 years). Results: Twenty-five percent of the travelers to moderate elevations developed acute mountain sickness, which occurred in 65% of travelers within the first 12 hours of arrival. Fifty-six percent of those with symptoms reduced their physical activity. The odds favoring acute mountain sickness were 3.5 times as large for visitors whose permanent residence was below 3000 feet elevation as for those whose residence was above 3000 feet; 2.8 times as large for visitors with previous symptoms of acute mountain sickness; and twice as large in travelers younger than 60 years. Women, obese persons, those in poor or average physical condition, and those with underlying lung disease also had a higher occurrence of acute mountain sickness (P < 0.05). Conclusions: Acute mountain sickness occurs in 25% of visitors to moderate altitudes and affects activity in most symptomatic visitors. Persons who are younger, less physically fit, live at sea level, have a history of acute mountain sickness, or have underlying lung problems more often develop these symptoms.

High-Altitude Pulmonary Edema Is Initially Caused by an Increase in Capillary Pressure

2001-04-24
Marco Maggiorini , Christian Mélot , Sébastien Pierre +7 more
Background —High-altitude pulmonary edema (HAPE) is characterized by severe pulmonary hypertension and bronchoalveolar lavage fluid changes indicative of inflammation. It is not known, however, whether the primary event is an … Background —High-altitude pulmonary edema (HAPE) is characterized by severe pulmonary hypertension and bronchoalveolar lavage fluid changes indicative of inflammation. It is not known, however, whether the primary event is an increase in pressure or an increase in permeability of the pulmonary capillaries. Methods and Results —We studied pulmonary hemodynamics, including capillary pressure determined by the occlusion method, and capillary permeability evaluated by the pulmonary transvascular escape of 67 Ga-labeled transferrin, in 16 subjects with a previous HAPE and in 14 control subjects, first at low altitude (490 m) and then within the first 48 hours of ascent to a high-altitude laboratory (4559 m). The HAPE-susceptible subjects, compared with the control subjects, had an enhanced pulmonary vasoreactivity to inspiratory hypoxia at low altitude and higher mean pulmonary artery pressures (37±2 versus 26±1 mm Hg, P &lt;0.001) and pulmonary capillary pressures (19±1 versus 13±1 mm Hg, P &lt;0.001) at high altitude. Nine of the susceptible subjects developed HAPE. All of them had a pulmonary capillary pressure &gt;19 mm Hg (range 20 to 26 mm Hg), whereas all 7 susceptible subjects without HAPE had a pulmonary capillary pressure &lt;19 mm Hg (range 14 to 18 mm Hg). The pulmonary transcapillary escape of radiolabeled transferrin increased slightly from low to high altitude in the HAPE-susceptible subjects but remained within the limits of normal and did not differ significantly from the control subjects. Conclusions —HAPE is initially caused by an increase in pulmonary capillary pressure.
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Acute High-Altitude Illnesses

2013-06-12
Peter Bärtsch , Erik R. Swenson
Persons who are not acclimatized to high altitudes and who ascend to 2500 m are at risk for acute high-altitude illnesses. This article reviews approaches to prevention (e.g., slow ascent, … Persons who are not acclimatized to high altitudes and who ascend to 2500 m are at risk for acute high-altitude illnesses. This article reviews approaches to prevention (e.g., slow ascent, inclusion of a rest day during ascent, and medications) and treatment.

Altitude adaptation in Tibetans caused by introgression of Denisovan-like DNA

2014-07-01
Emilia Huerta‐Sánchez , Xin Jin , Asan +7 more

Oxygen Sensing, Homeostasis, and Disease

2011-08-10
Gregg L. Semenza
Pathways that sense a reduction in available oxygen are critical in the adaptation to lower oxygen tensions at high altitude. Alterations in this system can contribute to the pathogenesis of … Pathways that sense a reduction in available oxygen are critical in the adaptation to lower oxygen tensions at high altitude. Alterations in this system can contribute to the pathogenesis of heart disease, cancer, stroke, chronic lung disease, and many other disorders.

THE INCIDENCE, IMPORTANCE, AND PROPHYLAXIS OF ACUTE MOUNTAIN SICKNESS

1976-11-01
Peter M. Hackett

Therapeutic potential of intermittent hypoxia: a matter of dose

2014-09-18
Angela Navarrete‐Opazo , Gordon S. Mitchell
Intermittent hypoxia (IH) has been the subject of considerable research in recent years, and triggers a bewildering array of both detrimental and beneficial effects in multiple physiological systems. Here, we … Intermittent hypoxia (IH) has been the subject of considerable research in recent years, and triggers a bewildering array of both detrimental and beneficial effects in multiple physiological systems. Here, we review the extensive literature concerning IH and its impact on the respiratory, cardiovascular, immune, metabolic, bone, and nervous systems. One major goal is to define relevant IH characteristics leading to safe, protective, and/or therapeutic effects vs. pathogenesis. To understand the impact of IH, it is essential to define critical characteristics of the IH protocol under investigation, including potentially the severity of hypoxia within episodes, the duration of hypoxic episodes, the number of hypoxic episodes per day, the pattern of presentation across time (e.g., within vs. consecutive vs. alternating days), and the cumulative time of exposure. Not surprisingly, severe/chronic IH protocols tend to be pathogenic, whereas any beneficial effects are more likely to arise from modest/acute IH exposures. Features of the IH protocol most highly associated with beneficial vs. pathogenic outcomes include the level of hypoxemia within episodes and the number of episodes per day. Modest hypoxia (9-16% inspired O2) and low cycle numbers (3-15 episodes per day) most often lead to beneficial effects without pathology, whereas severe hypoxia (2-8% inspired O2) and more episodes per day (48-2,400 episodes/day) elicit progressively greater pathology. Accumulating evidence suggests that "low dose" IH (modest hypoxia, few episodes) may be a simple, safe, and effective treatment with considerable therapeutic potential for multiple clinical disorders.

Prevention of High-Altitude Pulmonary Edema by Nifedipine

1991-10-31
Peter Bärtsch , Marco Maggiorini , Manfred Ritter +3 more
Exaggerated pulmonary-artery pressure due to hypoxic vasoconstriction is considered an important pathogenetic factor in high-altitude pulmonary edema. We previously found that nifedipine lowered pulmonary-artery pressure and improved exercise performance, gas … Exaggerated pulmonary-artery pressure due to hypoxic vasoconstriction is considered an important pathogenetic factor in high-altitude pulmonary edema. We previously found that nifedipine lowered pulmonary-artery pressure and improved exercise performance, gas exchange, and the radiographic manifestations of disease in patients with high-altitude pulmonary edema. We therefore hypothesized that the prophylactic administration of nifedipine would prevent its recurrence.
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Genetic Evidence for High-Altitude Adaptation in Tibet

2010-05-14
Tatum S. Simonson , Yingzhong Yang , Chad D. Huff +7 more
No Genetic Vertigo Peoples living in high altitudes have adapted to their situation (see the Perspective by Storz ). To identify gene regions that might have contributed to high-altitude adaptation … No Genetic Vertigo Peoples living in high altitudes have adapted to their situation (see the Perspective by Storz ). To identify gene regions that might have contributed to high-altitude adaptation in Tibetans, Simonson et al. (p. 72 , published online 13 May) conducted a genome scan of nucleotide polymorphism comparing Tibetans, Han Chinese, and Japanese, while Yi et al. (p. 75 ) performed comparable analyses on the coding regions of all genes—their exomes. Both studies converged on a gene, endothelial Per-Arnt-Sim domain protein 1 (also known as hypoxia-inducible factor 2 α), which has been linked to the regulation of red blood cell production. Other genes identified that were potentially under selection included adult and fetal hemoglobin and two functional candidate loci that were correlated with low hemoglobin concentration in Tibetans. Future detailed functional studies will now be required to examine the mechanistic underpinnings of physiological adaptation to high altitudes.

The Heart and Pulmonary Circulation at High Altitudes

2007-03-05
Dante Peñaloza , Javier Arias‐Stella
More than 140 million people worldwide live &gt;2500 m above sea level. Of them, 80 million live in Asia, and 35 million live in the Andean mountains. This latter region … More than 140 million people worldwide live &gt;2500 m above sea level. Of them, 80 million live in Asia, and 35 million live in the Andean mountains. This latter region has its major population density living above 3500 m. The primary objective of the present study is to review the physiology, pathology, pathogenesis, and clinical features of the heart and pulmonary circulation in healthy highlanders and patients with chronic mountain sickness. A systematic review of worldwide literature was undertaken, beginning with the pioneering work done in the Andes several decades ago. Original articles were analyzed in most cases and English abstracts or translations of articles written in Chinese were reviewed. Pulmonary hypertension in healthy highlanders is related to a delayed postnatal remodeling of the distal pulmonary arterial branches. The magnitude of pulmonary hypertension increases with the altitude level and the degree of exercise. There is reversal of pulmonary hypertension after prolonged residence at sea level. Chronic mountain sickness develops when the capacity for altitude adaptation is lost. These patients have moderate to severe pulmonary hypertension with accentuated hypoxemia and exaggerated polycythemia. The clinical picture of chronic mountain sickness differs from subacute mountain sickness and resembles other chronic altitude diseases described in China and Kyrgyzstan. The heart and pulmonary circulation in healthy highlanders have distinct features in comparison with residents at sea level. Chronic mountain sickness is a public health problem in the Andean mountains and other mountainous regions around the world. Therefore, dissemination of preventive and therapeutic measures is essential.
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Respiratory function tests; normal values at median altitudes and the prediction of normal results.

1959-04-01
Herbert I. Goldman , Margaret R. Becklake

Natural selection on <i>EPAS1</i> ( <i>HIF2α</i> ) associated with low hemoglobin concentration in Tibetan highlanders

2010-06-07
Cynthia M. Beall , Gianpiero L. Cavalleri , Libin Deng +7 more
By impairing both function and survival, the severe reduction in oxygen availability associated with high-altitude environments is likely to act as an agent of natural selection. We used genomic and … By impairing both function and survival, the severe reduction in oxygen availability associated with high-altitude environments is likely to act as an agent of natural selection. We used genomic and candidate gene approaches to search for evidence of such genetic selection. First, a genome-wide allelic differentiation scan (GWADS) comparing indigenous highlanders of the Tibetan Plateau (3,200–3,500 m) with closely related lowland Han revealed a genome-wide significant divergence across eight SNPs located near EPAS1 . This gene encodes the transcription factor HIF2α, which stimulates production of red blood cells and thus increases the concentration of hemoglobin in blood. Second, in a separate cohort of Tibetans residing at 4,200 m, we identified 31 EPAS1 SNPs in high linkage disequilibrium that correlated significantly with hemoglobin concentration. The sex-adjusted hemoglobin concentration was, on average, 0.8 g/dL lower in the major allele homozygotes compared with the heterozygotes. These findings were replicated in a third cohort of Tibetans residing at 4,300 m. The alleles associating with lower hemoglobin concentrations were correlated with the signal from the GWADS study and were observed at greatly elevated frequencies in the Tibetan cohorts compared with the Han. High hemoglobin concentrations are a cardinal feature of chronic mountain sickness offering one plausible mechanism for selection. Alternatively, as EPAS1 is pleiotropic in its effects, selection may have operated on some other aspect of the phenotype. Whichever of these explanations is correct, the evidence for genetic selection at the EPAS1 locus from the GWADS study is supported by the replicated studies associating function with the allelic variants.
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Two routes to functional adaptation: Tibetan and Andean high-altitude natives

2007-05-10
Cynthia M. Beall
Populations native to the Tibetan and Andean Plateaus are descended from colonizers who arrived perhaps 25,000 and 11,000 years ago, respectively. Both have been exposed to the opportunity for natural … Populations native to the Tibetan and Andean Plateaus are descended from colonizers who arrived perhaps 25,000 and 11,000 years ago, respectively. Both have been exposed to the opportunity for natural selection for traits that offset the unavoidable environmental stress of severe lifelong high-altitude hypoxia. This paper presents evidence that Tibetan and Andean high-altitude natives have adapted differently, as indicated by large quantitative differences in numerous physiological traits comprising the oxygen delivery process. These findings suggest the hypothesis that evolutionary processes have tinkered differently on the two founding populations and their descendents, with the result that the two followed different routes to the same functional outcome of successful oxygen delivery, long-term persistence and high function. Assessed on the basis of basal and maximal oxygen consumption, both populations avail themselves of essentially the full range of oxygen-using metabolism as populations at sea level, in contrast with the curtailed range available to visitors at high altitudes. Efforts to identify the genetic bases of these traits have included quantitative genetics, genetic admixture, and candidate gene approaches. These reveal generally more genetic variance in the Tibetan population and more potential for natural selection. There is evidence that natural selection is ongoing in the Tibetan population, where women estimated to have genotypes for high oxygen saturation of hemoglobin (and less physiological stress) have higher offspring survival. Identifying the genetic bases of these traits is crucial to discovering the steps along the Tibetan and Andean routes to functional adaptation.
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Consensus Statement on Chronic and Subacute High Altitude Diseases

2005-06-01
Fabiola León‐Velarde , Marco Maggiorini , John Τ. Reeves +7 more
Léon-Velarde, Fabiola, Marco Maggiorini, John T. Reeves, Almaz Aldashev, Ingrid Asmus, Luciano Bernardi, Ri-Li Ge, Peter Hackett, Toshio Kobayashi, Lorna G. Moore, Dante Penaloza, Jean-Paul Richalet, Robert Roach, Tianyi Wu, … Léon-Velarde, Fabiola, Marco Maggiorini, John T. Reeves, Almaz Aldashev, Ingrid Asmus, Luciano Bernardi, Ri-Li Ge, Peter Hackett, Toshio Kobayashi, Lorna G. Moore, Dante Penaloza, Jean-Paul Richalet, Robert Roach, Tianyi Wu, Enrique Vargas, Gustavo Zubieta-Castillo, and Gustavo Zubieta-Calleja. Consensus on high altitude diseases. High Alt Med Biol 6:147–157, 2005.—This is an international consensus statement of an ad hoc committee formed by the International Society for Mountain Medicine (ISMM) at the VI World Congress on Mountain Medicine and High Altitude Physiology (Xining, China; 2004) and represents the committee's interpretation of the current knowledge with regard to the most common chronic and subacute high altitude diseases. It has been developed by medical and scientific authorities from the committee experienced in the recognition and prevention of high altitude diseases and is based mainly on published, peer-reviewed articles. It is intended to include all legitimate criteria for choosing to use a specific method or procedure to diagnose or manage high altitude diseases. However, the ISMM recognizes that specific patient care decisions depend on the different geographic circumstances involved in the development of each chronic high altitude disease. These guidelines are established to inform the medical services on site who are directed to solve high altitude health problems about the definition, diagnosis, treatment, and prevention of the most common hychronic high altitude diseases. The health problems associated with life at high altitude are well documented, but health policies and procedures often do not reflect current state-of-the-art knowledge. Most of the cases of high altitude diseases are preventable if on-site personnel identify the condition and implement appropriate care.

Identifying Signatures of Natural Selection in Tibetan and Andean Populations Using Dense Genome Scan Data

2010-09-09
Abigail W. Bigham , Marc Bauchet , Dalila Pinto +7 more
High-altitude hypoxia (reduced inspired oxygen tension due to decreased barometric pressure) exerts severe physiological stress on the human body. Two high-altitude regions where humans have lived for millennia are the … High-altitude hypoxia (reduced inspired oxygen tension due to decreased barometric pressure) exerts severe physiological stress on the human body. Two high-altitude regions where humans have lived for millennia are the Andean Altiplano and the Tibetan Plateau. Populations living in these regions exhibit unique circulatory, respiratory, and hematological adaptations to life at high altitude. Although these responses have been well characterized physiologically, their underlying genetic basis remains unknown. We performed a genome scan to identify genes showing evidence of adaptation to hypoxia. We looked across each chromosome to identify genomic regions with previously unknown function with respect to altitude phenotypes. In addition, groups of genes functioning in oxygen metabolism and sensing were examined to test the hypothesis that particular pathways have been involved in genetic adaptation to altitude. Applying four population genetic statistics commonly used for detecting signatures of natural selection, we identified selection-nominated candidate genes and gene regions in these two populations (Andeans and Tibetans) separately. The Tibetan and Andean patterns of genetic adaptation are largely distinct from one another, with both populations showing evidence of positive natural selection in different genes or gene regions. Interestingly, one gene previously known to be important in cellular oxygen sensing, EGLN1 (also known as PHD2), shows evidence of positive selection in both Tibetans and Andeans. However, the pattern of variation for this gene differs between the two populations. Our results indicate that several key HIF-regulatory and targeted genes are responsible for adaptation to high altitude in Andeans and Tibetans, and several different chromosomal regions are implicated in the putative response to selection. These data suggest a genetic role in high-altitude adaption and provide a basis for future genotype/phenotype association studies necessary to confirm the role of selection-nominated candidate genes and gene regions in adaptation to altitude.
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Soluble transferrin receptor for the evaluation of erythropoiesis and iron status

2003-02-17
Yves Béguin
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Effect of altitude on oxygen binding by hemoglobin and on organic phosphate levels

1968-12-01
Claude Lenfant , John Torrance , Eugenia English +4 more
The relationship between oxygen dissociation and 2,3-diphosphoglycerate (2,3-DPG) in the red cell has been studied in subjects moving from low to high altitude and vice versa. Within 24 hr following … The relationship between oxygen dissociation and 2,3-diphosphoglycerate (2,3-DPG) in the red cell has been studied in subjects moving from low to high altitude and vice versa. Within 24 hr following the change in altitude there was a change in hemoglobin affinity for oxygen; this modification therefore represents an important rapid adaptive mechanism to anoxia. A parallel change occurred in the organic phosphate content of the red cell. While this study does not provide direct evidence of a cause-effect relationship, the data strongly suggest that with anoxia, the observed rise in organic phosphate content of the red cell is responsible for increased availability of oxygen to tissues.
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The Work of Breathing

1954-07-01
Arthur B. Otis

Effect of Altitude on the Heart and the Lungs

2007-11-05
Peter Bärtsch , J. Simon R. Gibbs
T his review focuses on the effects of altitude exposure from 1 to several days or weeks as occurs in tourists, trekkers, and mountaineers who visit high altitude and normally … T his review focuses on the effects of altitude exposure from 1 to several days or weeks as occurs in tourists, trekkers, and mountaineers who visit high altitude and normally reside near sea level.We briefly review the acute physiological adjustments and early acclimatization that occur in the cardiovascular system and the lungs of healthy individuals.These ensure life-sustaining oxygen delivery to the tissues despite a reduction in the partial pressure of inspired oxygen between 20% and 60% at 2500 and 8000 m, respectively.One of the acute adjustments, hypoxic pulmonary vasoconstriction (HPV), may be disadvantageous in those with a vigorous response and lead to 2 potentially lethal illnesses, high-altitude pulmonary edema (HAPE) and subacute mountain sickness (SAMS), which we present in more detail.Finally, on the basis of knowledge about the acute physiological adjustments and acclimatization and, when available, a review of the literature, we discuss the highaltitude tolerance of patients with coronary artery disease, congestive heart failure, arrhythmias, systemic hypertension, and pulmonary hypertension.
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Andean, Tibetan, and Ethiopian patterns of adaptation to high-altitude hypoxia

2006-01-06
Cynthia M. Beall
Research on humans at high-altitudes contributes to understanding the processes of human adaptation to the environment and evolution. The unique stress at high altitude is hypobaric hypoxia caused by the … Research on humans at high-altitudes contributes to understanding the processes of human adaptation to the environment and evolution. The unique stress at high altitude is hypobaric hypoxia caused by the fall in barometric pressure with increasing altitude and the consequently fewer oxygen molecules in a breath of air, as compared with sea level. The natural experiment of human colonization of high-altitude plateaus on three continents has resulted in two—perhaps three—quantitatively different arterial-oxygen-content phenotypes among indigenous Andean, Tibetan and Ethiopian high-altitude populations. This paper illustrates these contrasting phenotypes by presenting evidence for higher hemoglobin concentration and percent of oxygen saturation of hemoglobin among Andean highlanders as compared with Tibetans at the same altitude and evidence that Ethiopian highlanders do not differ from sea-level in these two traits. Evolutionary processes may have acted differently on the colonizing populations to cause the different patterns of adaptation. Hemoglobin concentration has significant heritability in Andean and Tibetan samples. Oxygen saturation has no heritability in the Andean sample, but does among Tibetans where an autosomal dominant major gene for higher oxygen saturation has been detected. Women estimated with high probability to have high oxygen saturation genotypes have more surviving children than women estimated with high probability to have the low oxygen saturation genotype. These findings suggest the hypothesis that ongoing natural selection is increasing the frequency of the high saturation allele at this major gene locus.
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Control of TH17/Treg Balance by Hypoxia-Inducible Factor 1

2011-08-27
Eric V. Dang , Joseph Barbi , Huang‐Yu Yang +7 more
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The cerebral effects of ascent to high altitudes

2009-01-20
Mark H. Wilson , Stanton Newman , Chris Imray

“Living high-training low”: effect of moderate-altitude acclimatization with low-altitude training on performance

1997-07-01
Benjamin D. Levine , James Stray‐Gundersen
Levine, Benjamin D., and James Stray-Gundersen.“Living high-training low”: effect of moderate-altitude acclimatization with low-altitude training on performance. J. Appl. Physiol. 83(1): 102–112, 1997.—The principal objective of this study was to … Levine, Benjamin D., and James Stray-Gundersen.“Living high-training low”: effect of moderate-altitude acclimatization with low-altitude training on performance. J. Appl. Physiol. 83(1): 102–112, 1997.—The principal objective of this study was to test the hypothesis that acclimatization to moderate altitude (2,500 m) plus training at low altitude (1,250 m), “living high-training low,” improves sea-level performance in well-trained runners more than an equivalent sea-level or altitude control. Thirty-nine competitive runners (27 men, 12 women) completed 1) a 2-wk lead-in phase, followed by 2) 4 wk of supervised training at sea level; and 3) 4 wk of field training camp randomized to three groups: “high-low” ( n = 13), living at moderate altitude (2,500 m) and training at low altitude (1,250 m); “high-high” ( n = 13), living and training at moderate altitude (2,500 m); or “low-low” ( n = 13), living and training in a mountain environment at sea level (150 m). A 5,000-m time trial was the primary measure of performance; laboratory outcomes included maximal O 2 uptake (V˙o 2 max ), anaerobic capacity (accumulated O 2 deficit), maximal steady state (MSS; ventilatory threshold), running economy, velocity at V˙o 2 max , and blood compartment volumes. Both altitude groups significantly increased V˙o 2 max (5%) in direct proportion to an increase in red cell mass volume (9%; r = 0.37, P &lt; 0.05), neither of which changed in the control. Five-kilometer time was improved by the field training camp only in the high-low group (13.4 ± 10 s), in direct proportion to the increase inV˙o 2 max ( r = 0.65, P &lt; 0.01). Velocity atV˙o 2 max and MSS also improved only in the high-low group. Four weeks of living high-training low improves sea-level running performance in trained runners due to altitude acclimatization (increase in red cell mass volume and V˙o 2 max ) and maintenance of sea-level training velocities, most likely accounting for the increase in velocity atV˙o 2 max and MSS.

Considerations of the physiological variables that determine the blood carboxyhemoglobin concentration in man.

1965-11-01
Ronald F. Coburn , Robert Förster , Peter B. Kane
were analyzed for CO concentrations with an infrared CO meter. This instrument has an error (SD) of 4-0.00004% CO and requires a 200-ml sample. These samples were col- lected during … were analyzed for CO concentrations with an infrared CO meter. This instrument has an error (SD) of 4-0.00004% CO and requires a 200-ml sample. These samples were col- lected during the summer of 1964. Smoking is prohibited in the areas where these samples were collected. We also measured the CO concentrations in air samples taken from smoke-filled conference rooms, a small nonventilated room that we purposely filled with smoke by burning cigarettes, and a rural area well away from automobile combustion. Diurnal changes in blood (COHb) were measured in one subject and compared with the changes in percentage of CO in his environment. Blood (COHb) was determined by a method in which gas extracted from a 2-ml blood sample is measured in the infrared CO meter. This method has an error (SD) of 40.03% (COHb)( 10).
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Sequencing of 50 Human Exomes Reveals Adaptation to High Altitude

2010-07-01
Xin Yi , Yu Liang , Emilia Huerta‐Sánchez +7 more
No Genetic Vertigo Peoples living in high altitudes have adapted to their situation (see the Perspective by Storz ). To identify gene regions that might have contributed to high-altitude adaptation … No Genetic Vertigo Peoples living in high altitudes have adapted to their situation (see the Perspective by Storz ). To identify gene regions that might have contributed to high-altitude adaptation in Tibetans, Simonson et al. (p. 72 , published online 13 May) conducted a genome scan of nucleotide polymorphism comparing Tibetans, Han Chinese, and Japanese, while Yi et al. (p. 75 ) performed comparable analyses on the coding regions of all genes—their exomes. Both studies converged on a gene, endothelial Per-Arnt-Sim domain protein 1 (also known as hypoxia-inducible factor 2 α), which has been linked to the regulation of red blood cell production. Other genes identified that were potentially under selection included adult and fetal hemoglobin and two functional candidate loci that were correlated with low hemoglobin concentration in Tibetans. Future detailed functional studies will now be required to examine the mechanistic underpinnings of physiological adaptation to high altitudes.
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The yak genome and adaptation to life at high altitude

2012-07-01
Qiang Qiu , Guojie Zhang , Tao Ma +7 more
Jianquan Liu and colleagues report the draft genome sequence of the domestic yak, Bos grunniens. Their comparative analyses with low-altitude cattle provide insights into high-altitude adaptation in the yak. Domestic … Jianquan Liu and colleagues report the draft genome sequence of the domestic yak, Bos grunniens. Their comparative analyses with low-altitude cattle provide insights into high-altitude adaptation in the yak. Domestic yaks (Bos grunniens) provide meat and other necessities for Tibetans living at high altitude on the Qinghai-Tibetan Plateau and in adjacent regions. Comparison between yak and the closely related low-altitude cattle (Bos taurus) is informative in studying animal adaptation to high altitude. Here, we present the draft genome sequence of a female domestic yak generated using Illumina-based technology at 65-fold coverage. Genomic comparisons between yak and cattle identify an expansion in yak of gene families related to sensory perception and energy metabolism, as well as an enrichment of protein domains involved in sensing the extracellular environment and hypoxic stress. Positively selected and rapidly evolving genes in the yak lineage are also found to be significantly enriched in functional categories and pathways related to hypoxia and nutrition metabolism. These findings may have important implications for understanding adaptation to high altitude in other animal species and for hypoxia-related diseases in humans.
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Muscle tissue adaptations to hypoxia

2001-09-15
Hans Hoppeler , Michael Vogt
SUMMARY This review reports on the effects of hypoxia on human skeletal muscle tissue. It was hypothesized in early reports that chronic hypoxia, as the main physiological stress during exposure … SUMMARY This review reports on the effects of hypoxia on human skeletal muscle tissue. It was hypothesized in early reports that chronic hypoxia, as the main physiological stress during exposure to altitude, per se might positively affect muscle oxidative capacity and capillarity. However, it is now established that sustained exposure to severe hypoxia has detrimental effects on muscle structure. Short-term effects on skeletal muscle structure can readily be observed after 2 months of acute exposure of lowlanders to severe hypoxia, e.g. during typical mountaineering expeditions to the Himalayas. The full range of phenotypic malleability of muscle tissue is demonstrated in people living permanently at high altitude (e.g. at La Paz, 3600–4000m). In addition, there is some evidence for genetic adaptations to hypoxia in high-altitude populations such as Tibetans and Quechuas, who have been exposed to altitudes in excess of 3500m for thousands of generations. The hallmark of muscle adaptation to hypoxia in all these cases is a decrease in muscle oxidative capacity concomitant with a decrease in aerobic work capacity. It is thought that local tissue hypoxia is an important adaptive stress for muscle tissue in exercise training, so these results seem contra-intuitive. Studies have therefore been conducted in which subjects were exposed to hypoxia only during exercise sessions. In this situation, the potentially negative effects of permanent hypoxic exposure and other confounding variables related to exposure to high altitude could be avoided. Training in hypoxia results, at the molecular level, in an upregulation of the regulatory subunit of hypoxia-inducible factor-1 (HIF-1). Possibly as a consequence of this upregulation of HIF-1, the levels mRNAs for myoglobin, for vascular endothelial growth factor and for glycolytic enzymes, such as phosphofructokinase, together with mitochondrial and capillary densities, increased in a hypoxia-dependent manner. Functional analyses revealed positive effects on V̇O2max (when measured at altitude) on maximal power output and on lean body mass. In addition to the positive effects of hypoxia training on athletic performance, there is some recent indication that hypoxia training has a positive effect on the risk factors for cardiovascular disease.

Arterial Blood Gases and Oxygen Content in Climbers on Mount Everest

2009-01-07
Michael P. W. Grocott , Daniel Martín , Denny Levett +3 more
The level of environmental hypobaric hypoxia that affects climbers at the summit of Mount Everest (8848 m [29,029 ft]) is close to the limit of tolerance by humans. We performed … The level of environmental hypobaric hypoxia that affects climbers at the summit of Mount Everest (8848 m [29,029 ft]) is close to the limit of tolerance by humans. We performed direct field measurements of arterial blood gases in climbers breathing ambient air on Mount Everest.We obtained samples of arterial blood from 10 climbers during their ascent to and descent from the summit of Mount Everest. The partial pressures of arterial oxygen (PaO(2)) and carbon dioxide (PaCO(2)), pH, and hemoglobin and lactate concentrations were measured. The arterial oxygen saturation (SaO(2)), bicarbonate concentration, base excess, and alveolar-arterial oxygen difference were calculated.PaO(2) fell with increasing altitude, whereas SaO(2) was relatively stable. The hemoglobin concentration increased such that the oxygen content of arterial blood was maintained at or above sea-level values until the climbers reached an elevation of 7100 m (23,294 ft). In four samples taken at 8400 m (27,559 ft)--at which altitude the barometric pressure was 272 mm Hg (36.3 kPa)--the mean PaO(2) in subjects breathing ambient air was 24.6 mm Hg (3.28 kPa), with a range of 19.1 to 29.5 mm Hg (2.55 to 3.93 kPa). The mean PaCO(2) was 13.3 mm Hg (1.77 kPa), with a range of 10.3 to 15.7 mm Hg (1.37 to 2.09 kPa). At 8400 m, the mean arterial oxygen content was 26% lower than it was at 7100 m (145.8 ml per liter as compared with 197.1 ml per liter). The mean calculated alveolar-arterial oxygen difference was 5.4 mm Hg (0.72 kPa).The elevated alveolar-arterial oxygen difference that is seen in subjects who are in conditions of extreme hypoxia may represent a degree of subclinical high-altitude pulmonary edema or a functional limitation in pulmonary diffusion.
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Contaminated and Natural Lead Environments of Man

1965-09-01
Clair C. Patterson
(1965). Contaminated and Natural Lead Environments of Man. Archives of Environmental Health: An International Journal: Vol. 11, No. 3, pp. 344-360. (1965). Contaminated and Natural Lead Environments of Man. Archives of Environmental Health: An International Journal: Vol. 11, No. 3, pp. 344-360.

High-altitude illness

2003-06-01
Buddha Basnyat , David R. Murdoch

Molecular adaptations in human skeletal muscle to endurance training under simulated hypoxic conditions

2001-07-01
Michael Vogt , A. Puntschart , Jürgen Geiser +3 more
This study was performed to explore changes in gene expression as a consequence of exercise training at two levels of intensity under normoxic and normobaric hypoxic conditions (corresponding to an … This study was performed to explore changes in gene expression as a consequence of exercise training at two levels of intensity under normoxic and normobaric hypoxic conditions (corresponding to an altitude of 3,850 m). Four groups of human subjects trained five times a week for a total of 6 wk on a bicycle ergometer. Muscle biopsies were taken, and performance tests were carried out before and after the training period. Similar increases in maximal O 2 uptake (8.3–13.1%) and maximal power output (11.4–20.8%) were found in all groups. RT-PCR revealed elevated mRNA concentrations of the α-subunit of hypoxia-inducible factor 1 (HIF-1) after both high- (+82.4%) and low (+78.4%)-intensity training under hypoxic conditions. The mRNA of HIF-1α 736 , a splice variant of HIF-1α newly detected in human skeletal muscle, was shown to be changed in a similar pattern as HIF-1α. Increased mRNA contents of myoglobin (+72.2%) and vascular endothelial growth factor (+52.4%) were evoked only after high-intensity training in hypoxia. Augmented mRNA levels of oxidative enzymes, phosphofructokinase, and heat shock protein 70 were found after high-intensity training under both hypoxic and normoxic conditions. Our findings suggest that HIF-1 is specifically involved in the regulation of muscle adaptations after hypoxia training. Fine-tuning of the training response is recognized at the molecular level, and with less sensitivity also at the structural level, but not at global functional responses like maximal O 2 uptake or maximal power output.

Rat pulmonary circulation after chronic hypoxia: hemodynamic and structural features

1979-06-01
Marlene Rabinovitch , W. Gamble , Alexander S. Nadas +2 more
In 55 Sprague-Dawley rats (mean wt, 277 +/- 6.2 g) exposed to hypobaric hypoxia (air at 380 mmHg), and 23 weight-matched controls kept in room air, pulmonary and systemic artery … In 55 Sprague-Dawley rats (mean wt, 277 +/- 6.2 g) exposed to hypobaric hypoxia (air at 380 mmHg), and 23 weight-matched controls kept in room air, pulmonary and systemic artery pressures were measured daily for 2 wk via indwelling catheters. After each day of exposure, 1 or 2 hypoxic rats, to a total of 20, and 5 control rats were killed during the experiment. In these rats, the pulmonary arterial tree was injected post mortem with barium-gelatin and inflated with formaldehyde solution, and three structural features were quantified microscopically: 1) abnormal extension of muscle into peripheral arteries where it is not normally present (EMPA); 2) increased wall thickness of the normally muscular arteries, expressed as a percentage of external diameter (%WT); and 3) reduction in artery number expressed as an increase in the ratio of alveoli to arteries (A/a). Mean pulmonary artery pressure (Ppa) rose significantly after day 3 of hypoxic exposure (P less than 0.05) and had doubled by day 14; the mean systemic artery pressure (Psa) of hypoxic rats and Ppa and Psa of control rats were unchanged. The level of Ppa correlated with the degree of structural changes; for EMPA, r = 0.84; for %WT, r = 0.64; and for A/a, r = 0.73 (P less than 0.001 in all.

Iodine Deficiency in 2007: Global Progress since 2003

2008-09-01
Bruno de Benoist , Erin McLean , Maria Andersson +1 more
Background Iodine deficiency is a global public health problem, and estimates of the extent of the problem were last produced in 2003. Objectives To provide updated global estimates of the … Background Iodine deficiency is a global public health problem, and estimates of the extent of the problem were last produced in 2003. Objectives To provide updated global estimates of the magnitude of iodine deficiency in 2007, to assess progress since 2003, and to provide information on gaps in the data available. Methods Recently published, nationally representative data on urinary iodine (UI) in school-age children collected between 1997 and 2006 were used to update country estimates of iodine nutrition. These estimates, alongside the 2003 estimates for the remaining countries without new data, were used to generate updated global and regional estimates of iodine nutrition. The median UI was used to classify countries according to the public health significance of their iodine nutrition status. Progress was measured by comparing current prevalence figures with those from 2003. The data available for pregnant women by year of survey were also assessed. Results New UI data in school-age children were available for 41 countries, representing 45.4% of the world's school-age children. These data, along with previous country estimates for 89 countries, are the basis for the estimates and represent 91.1% of this population group. An estimated 31.5% of school-age children (266 million) have insufficient iodine intake. In the general population, 2 billion people have insufficient iodine intake. The number of countries where iodine deficiency is a public health problem is 47. Progress has been made: 12 countries have progressed to optimal iodine status, and the percentage of school-age children at risk of iodine deficiency has decreased by 5%. However, iodine intake is more than adequate, or even excessive, in 34 countries: an increase from 27 in 2003. There are insufficient data to estimate the global prevalence of iodine deficiency in pregnant women. Conclusions Global progress in controlling iodine deficiency has been made since 2003, but efforts need to be accelerated in order to eliminate this debilitating health issue that affects almost one in three individuals globally. Surveillance systems need to be strengthened to monitor both low and excessive intakes of iodine.

Acute Mountain Sickness

1969-01-23
Inder Singh , P K Khanna , M. C. Srivastava +3 more
Observations on acute mountain sickness occurring between 11,000 and 18,000 feet, in 1925 men, 18, to 53 years old, showed no direct relation between altitude and severity of illness; mild, … Observations on acute mountain sickness occurring between 11,000 and 18,000 feet, in 1925 men, 18, to 53 years old, showed no direct relation between altitude and severity of illness; mild, moderate and severe cases occurred at all altitudes. A time lag of six to 96 hours between arrival and onset of symptoms ruled out any direct relation between hypoxia and acute mountain sickness. During this period there was clinical evidence of respiratory dysfunction with slow, irregular or Cheyne—Stokes breathing, pulmonary congestion and antidiuresis. In one biopsy and two autopsy studies there was evidence of cerebral edema. Diuresis induced with furosemide provided effective routine therapy. Morphine and betamethasone were used as additional aids in severe cases. Clinical features of acute mountain sickness were ascribed to hypoxia, pulmonary congestion, increased cerebral blood flow, increased cerebrospinal-fluid pressure and cerebral edema.

Acute high-altitude sickness

2017-01-31
Andrew M. Luks , Erik R. Swenson , Peter Bärtsch
At any point 1–5 days following ascent to altitudes ≥2500 m, individuals are at risk of developing one of three forms of acute altitude illness: acute mountain sickness, a syndrome … At any point 1–5 days following ascent to altitudes ≥2500 m, individuals are at risk of developing one of three forms of acute altitude illness: acute mountain sickness, a syndrome of nonspecific symptoms including headache, lassitude, dizziness and nausea; high-altitude cerebral oedema, a potentially fatal illness characterised by ataxia, decreased consciousness and characteristic changes on magnetic resonance imaging; and high-altitude pulmonary oedema, a noncardiogenic form of pulmonary oedema resulting from excessive hypoxic pulmonary vasoconstriction which can be fatal if not recognised and treated promptly. This review provides detailed information about each of these important clinical entities. After reviewing the clinical features, epidemiology and current understanding of the pathophysiology of each disorder, we describe the current pharmacological and nonpharmacological approaches to the prevention and treatment of these diseases.
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Prevalence and Ethnic Pattern of Diabetes and Prediabetes in China in 2013

2017-06-27
Limin Wang , Pei Gao , Mei Zhang +7 more
Previous studies have shown increasing prevalence of diabetes in China, which now has the world's largest diabetes epidemic.To estimate the recent prevalence and to investigate the ethnic variation of diabetes … Previous studies have shown increasing prevalence of diabetes in China, which now has the world's largest diabetes epidemic.To estimate the recent prevalence and to investigate the ethnic variation of diabetes and prediabetes in the Chinese adult population.A nationally representative cross-sectional survey in 2013 in mainland China, which consisted of 170 287 participants.Fasting plasma glucose and hemoglobin A1c levels were measured for all participants. A 2-hour oral glucose tolerance test was conducted for all participants without diagnosed diabetes.Primary outcomes were total diabetes and prediabetes defined according to the 2010 American Diabetes Association criteria. Awareness and treatment were also evaluated. Hemoglobin A1c concentration of less than 7.0% among treated diabetes patients was considered adequate glycemic control. Minority ethnic groups in China with at least 1000 participants (Tibetan, Zhuang, Manchu, Uyghur, and Muslim) were compared with Han participants.Among the Chinese adult population, the estimated standardized prevalence of total diagnosed and undiagnosed diabetes was 10.9% (95% CI, 10.4%-11.5%); that of diagnosed diabetes, 4.0% (95% CI, 3.6%-4.3%); and that of prediabetes, 35.7% (95% CI, 34.1%-37.4%). Among persons with diabetes, 36.5% (95% CI, 34.3%-38.6%) were aware of their diagnosis and 32.2% (95% CI, 30.1%-34.2%) were treated; 49.2% (95% CI, 46.9%-51.5%) of patients treated had adequate glycemic control. Tibetan and Muslim Chinese had significantly lower crude prevalence of diabetes than Han participants (14.7% [95% CI, 14.6%-14.9%] for Han, 4.3% [95% CI, 3.5%-5.0%] for Tibetan, and 10.6% [95% CI, 9.3%-11.9%] for Muslim; P < .001 for Tibetan and Muslim compared with Han). In the multivariable logistic models, the adjusted odds ratios compared with Han participants were 0.42 (95% CI, 0.35-0.50) for diabetes and 0.77 (95% CI, 0.71-0.84) for prediabetes for Tibetan Chinese and 0.73 (95% CI, 0.63-0.85) for diabetes and 0.78 (95% CI, 0.71-0.86) for prediabetes in Muslim Chinese.Among adults in China, the estimated overall prevalence of diabetes was 10.9%, and that for prediabetes was 35.7%. Differences from previous estimates for 2010 may be due to an alternate method of measuring hemoglobin A1c.

High-Altitude Illness

2001-07-12
Peter H. Hackett , Robert C. Roach
The term “high-altitude illness” is used to describe the cerebral and pulmonary syndromes that can develop in unacclimatized persons shortly after ascent to high altitude. Acute mountain sickness and high-altitude … The term “high-altitude illness” is used to describe the cerebral and pulmonary syndromes that can develop in unacclimatized persons shortly after ascent to high altitude. Acute mountain sickness and high-altitude cerebral edema refer to the cerebral abnormalities, and high-altitude pulmonary edema to the pulmonary abnormalities. Because millions of visitors travel to high-altitude locations each year, acute mountain sickness is a public health problem and has economic consequences, especially for the ski industry. High-altitude pulmonary edema and high-altitude cerebral edema, though uncommon, are potentially fatal. High-altitude illness also provides a useful model for studying the pathophysiological process of hypoxia in an . . .

The 2018 Lake Louise Acute Mountain Sickness Score

2018-03-01
Robert C. Roach , Peter H. Hackett , O Oelz +7 more
Roach, Robert C., Peter H. Hackett, Oswald Oelz, Peter Bärtsch, Andrew M. Luks, Martin J. MacInnis, J. Kenneth Baillie, and The Lake Louise AMS Score Consensus Committee. The 2018 Lake … Roach, Robert C., Peter H. Hackett, Oswald Oelz, Peter Bärtsch, Andrew M. Luks, Martin J. MacInnis, J. Kenneth Baillie, and The Lake Louise AMS Score Consensus Committee. The 2018 Lake Louise Acute Mountain Sickness Score. High Alt Med Biol 19:1-4, 2018.- The Lake Louise Acute Mountain Sickness (AMS) scoring system has been a useful research tool since first published in 1991. Recent studies have shown that disturbed sleep at altitude, one of the five symptoms scored for AMS, is more likely due to altitude hypoxia per se, and is not closely related to AMS. To address this issue, and also to evaluate the Lake Louise AMS score in light of decades of experience, experts in high altitude research undertook to revise the score. We here present an international consensus statement resulting from online discussions and meetings at the International Society of Mountain Medicine World Congress in Bolzano, Italy, in May 2014 and at the International Hypoxia Symposium in Lake Louise, Canada, in February 2015. The consensus group has revised the score to eliminate disturbed sleep as a questionnaire item, and has updated instructions for use of the score.
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Prevalence and impact of diabetes among people infected with SARS-CoV-2

2020-03-28
Gian Paolo Fadini , Mario Luca Morieri , Enrico Longato +1 more
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The pathway for oxygen : structure and function in the mammalian respiratory system

1984-01-01
Ewald R. Weibel
It is rare indeed for one book to be both a first-rate classroom text and a major contribution to scholarship. Pathway for Oxygen is such a book, offering a new … It is rare indeed for one book to be both a first-rate classroom text and a major contribution to scholarship. Pathway for Oxygen is such a book, offering a new approach to respiratory physiology and morphology that quantitatively links the two. Professionalism in science has led to a compartmentalization of biology. Function is the domain of the physiologist, structure that of the morphologist, and they often operate with vastly disparate concepts and procedures. Yet the performance of the respiratory system depends both on structural and on functional properties that cannot be separated. The first chapter of Pathway for Oxygen engages the student with the design and function of the vertebrate respiratory organs from a comparative viewpoint. The second chapter adds to that foundation the link between cell energetics and oxygen needs of the whole animal. With Chapter 3 the excitement begins--new ideas, fresh attacks on old problems, and a fuller account of the power of the quantitative approach Dr. Weibel has pioneered. Pathway for Oxygen will be read eagerly by medical students, graduate students, advanced undergraduates in zoology--and by their professors.

Enhancing muscle strength and body composition after low-load resistance with blood flow restriction and hypoxia in untrained males

2025-06-24
Arunya Buttichak , Chaiyawat Namboonlue , Sarawut Poca +2 more | Retos
Introduction: High-intensity resistance training may elevate the risk of musculoskeletal injuries and hinder optimal performance execution. Objective: This study compared the effects of low-load resistance training under blood flow restriction … Introduction: High-intensity resistance training may elevate the risk of musculoskeletal injuries and hinder optimal performance execution. Objective: This study compared the effects of low-load resistance training under blood flow restriction (BFR) and hypoxia (HYP) on body composition, strength, and endurance in untrained male college students. Methodology: Forty-five male college students from Ubon Ratchathani Rajabhat University were purposively sampled and matched into three groups (n = 15): 1) high-load resistance training (HLRT), 2) low-load resistance combined with blood flow restriction training (LLBFR), and 3) low-load resistance combined with hypoxic training (LLHYP). All groups trained three times weekly for five weeks. Results: After five weeks of training, all groups showed significant improvements in fat-free mass, skeletal muscle mass and performance outcome (p &lt; 0.05). The LLHYP group also exhibited significantly reduced skinfold thickness and greater arm circumference (p &lt; 0.05). All groups improved strength and endurance, but LLHYP demonstrated significantly greater endurance than HLRT in both exercises (p = 0.021 and 0.003, respectively) and outperformed LLBFR in the dip machine (p = 0.032). Discussion: Findings support that LLBFR and LLHYP can produce similar strength and body composition outcomes as HLRT over a short term. LLHYP, in particular, showed superior benefits in endurance, possibly due to hypoxia-related physiological adaptations. Conclusions: Low-load resistance training with BFR and HYP effectively enhanced body composition, strength, and endurance of the biceps and triceps. This approach may offer a safer alternative for untrained male students.

Effects of high-intensity interval training under hypoxic conditions on energy system performance in collegiate football players

2025-06-24
Jukdao Potisaen , Traimit Potisan , Supanithi Khumprommarach | Retos
Introduction: High-Intensity Interval Training (HIIT) is widely recognized for enhancing athletic performance. However, whether simulated hypoxic conditions amplify the physiological effects of HIIT especially in sports like football that rely … Introduction: High-Intensity Interval Training (HIIT) is widely recognized for enhancing athletic performance. However, whether simulated hypoxic conditions amplify the physiological effects of HIIT especially in sports like football that rely on multiple energy systems, remains underexplored. Objective: To investigate whether simulated hypoxic HIIT elicits greater improvements in aerobic and anaerobic performance compared to normoxic HIIT and standard training in collegiate football players. Methodology: Twenty-four male collegiate football players were randomly assigned to three groups: Hypoxic HIIT, Normoxic HIIT, or Control. Over a four-week intervention period, the experimental groups engaged in sport-specific HIIT under their respective environmental conditions, while all participants continued standard team training. Pre- and post-training assessments included VO₂max, Yo-Yo Intermittent Recovery Test Level 1 (Yo-Yo IR1), Running-Based Anaerobic Sprint Test (RAST), and 30-meter flying sprint. Results: The Hypoxic HIIT group showed significant improvements in VO₂max and Yo-Yo IR1 distance (p &lt; 0.01), with moderate gains in RAST peak power. Minimal changes were observed in ATP-PC system performance. These adaptations exceeded those observed in the Normoxic and Control groups. Discussion: The findings indicate that hypoxic stress provides an additive stimulus to aerobic conditioning. This aligns with existing literature on the role of hypoxia in enhancing oxygen transport, mitochondrial function, and endurance capacity. Conclusions: Simulated hypoxic HIIT effectively enhances aerobic capacity and selectively improves anaerobic performance. It represents a time-efficient and evidence-based conditioning strategy for competitive football.

The Effects of Hot Springs on Cognitive Function

2025-06-24
Masaharu Maeda | Higher Brain Function Research

Decision-Time Learning and Planning Integrated Control for the Mild Hyperbaric Chamber

2025-06-23
Nan Zhang , Qijing Lin , Zhuangde Jiang | Algorithms
Plateau hypoxia represents a type of hypobaric hypoxia caused by reduced atmospheric pressure at high altitudes. Pressurization therapy is one of the most effective methods for alleviating acute high-altitude sickness. … Plateau hypoxia represents a type of hypobaric hypoxia caused by reduced atmospheric pressure at high altitudes. Pressurization therapy is one of the most effective methods for alleviating acute high-altitude sickness. This study focuses on the development of an advanced control system for a vehicle-mounted mild hyperbaric chamber (MHBC) designed for the prevention and treatment of plateau hypoxia. Conventional control methods struggle to cope with the high complexity and inherent uncertainties associated with MHBC control tasks, thereby motivating the exploration of sequential decision-making approaches such as reinforcement learning. Nevertheless, the application of sequential decision-making in MHBC control encounters several challenges, including data inefficiency and non-stationary dynamics. The system’s low tolerance for trial-and-error may lead to component damage or unsafe operating conditions, and anomalies such as valve failure can emerge during long-term operation, compromising system stability. To address these challenges, this study proposes a decision-time learning and planning integrated framework for MHBC control. Specifically, an innovative latent model embedding decision-time learning is designed for system identification, separately managing system uncertainties to fine-tune the model output. Furthermore, a decision-time planning algorithm is developed and the planning process is further guided by incorporating a value network and an enhanced online policy. Experimental results demonstrate that the proposed decision-time learning and planning integrated approaches achieve notable performance in MHBC control.

Thermophiles, Thick‐Walled Bacteria, and Pseudomonads in High‐Altitude Gut Microbiota

2025-06-23
Fang Yan , Shimin Wu , Wenqiang Yuan +3 more | Journal of Gastroenterology and Hepatology
ABSTRACT Background and Aim High‐altitude environments are characterized by low oxygen and reduced low pressure, which impose significant physiological challenges on organisms. Among various adaptive systems, the intestinal flora plays … ABSTRACT Background and Aim High‐altitude environments are characterized by low oxygen and reduced low pressure, which impose significant physiological challenges on organisms. Among various adaptive systems, the intestinal flora plays a crucial role in maintaining gut health and barrier integrity function under such conditions. This study aimed to elucidate the regulatory mechanisms of intestinal flora in high‐altitude environments, focusing on downregulating intracellular Bone Morphogenetic Protein 4 (BMP4) to influence glycolysis metabolism, thereby affecting intercellular communication of the intestinal mucosal barrier and matrix remodeling. Methods High‐altitude mouse intestinal flora composition and function were analyzed using 16S rRNA and metagenomic sequencing. Additionally, single‐cell sequencing was employed to examine cell population communication and gene expression differences between normal and high‐altitude mouse intestinal tissues. Results Single‐cell sequencing showed significantly reduced interactions between intestinal fibroblasts and epithelial cells in high‐altitude mice, accompanied by a marked increase in BMP4 expression. Overexpression of BMP4 was found to activate the glycolysis pathway. Gut microbiota metabolites, including secondary bile acids, lactic acid, and butyrate, exhibited protective effects on hypoxia‐induced intestinal mucosal barrier injury, with butyrate showing the most prominent effect. Under hypoxic conditions, butyrate suppressed the BMP4/glycolysis pathway, thereby alleviating hypoxia‐induced intestinal mucosal barrier damage. Conclusion This study uncovered a novel mechanism by which the gut microbiota in high‐altitude environments modulate glycolysis metabolism through BMP4 downregulation, thereby affecting intercellular communication and matrix remodeling within the intestinal mucosal barrier.

Validity of pulse oximetry measures for heart rate and oxygen saturation during profound hypoxia in normobaric simulated extreme altitudes

2025-06-23
Harald Vikne , Jon Arild Kjeserud , Willy Westgaard +5 more | PLoS ONE
Commercial pulse oximeters may not be well calibrated for oxygen saturations below 70%, conditions that may be met in high altitude aviation and mountaineering. We therefore examined the bias and … Commercial pulse oximeters may not be well calibrated for oxygen saturations below 70%, conditions that may be met in high altitude aviation and mountaineering. We therefore examined the bias and variability of heart rate (HR) and blood oxygen saturation (SpO2) of four different pulse oximeters (PO) at arterial blood oxygen saturation (SaO2) between 55 and 100%. Seventeen healthy participants (age 33 ± 11 (mean ± standard deviation (SD)) yr) were exposed to controlled desaturation at rest by stepwise reduction of the oxygen fraction in the breathing air between 20.9 and 8%. Parallel measurements of HR (n = 383) and blood oxygen saturation (n = 304) from four pulse oximeters (RAD-97, PM100N, M7500 and Nell1-SR) and from reference instruments (by hemoximetry and electrocardiography (ECG)) were taken during the exposure. The validity was assessed in intervals of 55-70%, 70-85% and 85-100% SaO2 using the Bland-Altman method (bias and 95% limits of agreement (LoA)) and the root mean square error for variability. The demarcation criteria for agreement between methods were ±6 percentage points O2Hb saturation and ±6 bpm HR. At the 85-100% SaO2 interval, all POs but the Nell1-SR were in agreement with the reference for O2 saturation. Only M7500 agreed with the reference for the 70-85% interval and none of the POs were in agreement with the reference for the 55-70% interval. The pulse oximeters and ECG were not in agreement for HR at neither the 55-70% nor the 85-100% interval but agreed at the 70-85% interval except the RAD-97. All pulse oximeters increased the bias or the variability for SpO2 significantly by reductions in oxygen saturation, while no systematic differences were found for HR. The study shows that medically approved pulse oximeters are not in agreement with reference measurements of neither blood oxygen saturation nor HR at SaO2 levels below 70%, and their readings should therefore be interpreted cautiously during severe desaturation.

Acute high-altitude hypoxia induced NLRP3 inflammasome activation in pulmonary artery smooth muscle cells by BMAL1 targeting mitochondrial VDAC1-mediated MtDNA leakage

2025-06-22
Siyuan He , Ying-Rui Bu , Jin Xu +6 more | APOPTOSIS

Comparison of early postnatal hemodynamics in neonates born at high-altitude or low-altitude using USCOM: a pilot study

2025-06-21
Yue Yang , Gong Zhuo , Wenchao Hong +3 more | European Journal of Pediatrics
This study's purpose is to compare early postnatal hemodynamics between neonates from high- and low-altitude regions using Ultrasound Cardiac Output Monitor (USCOM) measurements. We prospectively enrolled hemodynamically stable neonates from … This study's purpose is to compare early postnatal hemodynamics between neonates from high- and low-altitude regions using Ultrasound Cardiac Output Monitor (USCOM) measurements. We prospectively enrolled hemodynamically stable neonates from Shanghai Children's Hospital (low-altitude group, sea level) and People's Hospital of Shigatse City (high-altitude group, 3850 m) between January and June 2024. Hemodynamic parameters derived from USCOM and clinical data (including oxygen saturation, heart rate, blood pressure, and hemoglobin levels) were obtained on postnatal day 7. The Mann-Whitney U test was employed to compare the differences between groups. The analysis included 80 neonates (40 per group) with comparable baseline characteristics, including gender, gestational age, weight, length, hemoglobin, oxygen carrying capacity, heart rate, and diastolic and mean blood pressure (p > 0.05). Compared to low-altitude group, high-altitude group demonstrated significantly higher stroke volume index (SVI), cardiac output (CO), cardiac index (CI), Smith-Madigan inotropy index (SMII), and systolic blood pressure (p < 0.05). Subgroup analysis indicated that preterm infants in the high-altitude group showed increased SVI, CO, CI, and SMII with lower systemic vascular resistance index (SVRI) (p < 0.05), whereas term infants in the group exhibited elevated CI, SMII, and systolic and mean blood pressure, compared to infants in the low-altitude group, respectively (p < 0.05). Neonates born at high altitude may maintain circulatory adaptation through enhanced myocardial contractility and cardiac performance, while the compensatory responses seem to differ between preterm infants (Frank-Starling mechanism) and term infants (sympathetic-driven regulation). • Neonates born at high altitude demonstrate lower SpO2 and cardiovascular adaptations to hypobaric hypoxia. • While USCOM enables non-invasive hemodynamic monitoring in neonates, physiological differences at different altitude levels may affect the interpretation of USCOM measurements. • First USCOM-derived comparison reveals elevated cardiac efficiency (higher SVI, CI, and SMII) in neonates born at high-altitude. • The compensatory mechanisms for hypobaric hypoxia differed according to cardiovascular maturity: preterm infants relied on the Frank-Starling mechanism, whereas term infants exhibited sympathetic activation.

Health effects of atmospheric pressure fluctuations: a review of biometeorological research

2025-06-18
N. V. Kuzmenko , В. А. Цырлин , М. Г. Плисс +1 more | International Journal of Biometeorology

[Changes of intestinal microflora in patients with colorectal benign and malignant tumors in high altitude area and comparison with the normal population in low altitude area].

2025-06-18
Dong Soo Han , Yangjin Ciren , Qiuyu Li +1 more | PubMed
To analyze the changes of intestinal flora in patients with benign and malignant colorectal tumors in high altitude areas and to compare them with the normal population in low altitude … To analyze the changes of intestinal flora in patients with benign and malignant colorectal tumors in high altitude areas and to compare them with the normal population in low altitude areas. The clinical data of 61 patients who underwent colonoscopy in the People' s Hospital of Tibet Autonomous Region from 2020 to 2022 were collected as the high altitude group. According to the colonoscopy results, they were divided into control group (29 cases), non-adenomatous polyp group (12 cases), adenoma group (10 cases), colorectal cancer group (10 cases). 17 patients who had negative colonoscopy results in the Peking University Third Hospital during the same period were collected as the low altitude control group. Before bowel preparation for colonoscopy, the fecal samples were collected. Then the DNA of bacteria in the fecal samples was extracted. The V3-V4 variable region of the 16S rRNA gene was PCR amplified and high-throughput sequenced. The species diversity of fecal flora was analyzed. Alpha diversity analysis showed that the species diversity of samples from the high altitude colorectal cancer group differed statistically from that of the high altitude non-adenomatous polyp group and the low altitude control group, and the species diversity of colorectal samples from the high altitude colorectal cancer group was higher than that of the other two groups. While beta diversity showed no significant difference among the five groups. Differences were found in phylum level analysis that the abundance of Actinobacteriota in the low altitude control group was significantly lower than those in each group of the high altitude area, while the abundance of Actinobacteriota in the colorectal cancer group was significantly lower than those in the other 3 groups of the high altitude area. Differences were found in genus level analysis that the abundance of Bacteroides, Phascclarctobacterium and Lachnoclostridium in the low altitude control group was significantly higher than those of all the groups in the high altitude area; the abundance of Blautia and Collinsella in the high altitude control group was the highest. Lactobacillus was not detected in the low altitude control group, while there was a highly significant difference (P < 0.05) in the level of Lactobacillus in the four groups of high altitude area, and the abundance of Lactobacillus was significantly higher in the control group than those of the other three groups. In the four groups of samples at high altitude, the abundance of Bifidobacterium decreased significantly, while the abundance of Christensenellaceae_R-7_group increased significantly. Compared with the high and low altitude controls, the diversity and abundance of intestinal flora in patients with colorectal benign and malignant tumors at high altitudes are different. And the abundance of species are also diffe-rent at the phylum and genus levels, suggesting that altitude factors may have some influence on intestinal flora.

Hypoxia preconditioned MSC exosomes attenuate high-altitude cerebral edema via the miR-125a-5p/RTEF-1 axis to protect vascular endothelial cells

2025-06-18
Jiachen Zuo , Jun Liang , Nan Hu +7 more | Bioactive Materials

Adult hypoxic-ischemic encephalopathy

2025-06-18
Abdulkhaleq BinNuhaid | Radiopaedia.org

Metabolomics Signatures of a Respiratory Tract Infection During an Altitude Training Camp in Elite Rowers

2025-06-17
Félix Boudry , Fabienne Durand , Corentine Goossens | Metabolites
Background: Respiratory pathologies, such as COVID-19 and bronchitis, pose significant challenges for high-level athletes, particularly during demanding altitude training camps. Metabolomics offers a promising approach for early detection of such … Background: Respiratory pathologies, such as COVID-19 and bronchitis, pose significant challenges for high-level athletes, particularly during demanding altitude training camps. Metabolomics offers a promising approach for early detection of such pathologies, potentially minimizing their impact on performance. This study investigates the metabolic differences between athletes with and without respiratory illnesses during an altitude training camp using urine samples and multivariate analysis. Methods: Twenty-seven elite rowers (15 males, 12 females) participated in a 12-day altitude training camp at 1850 m. Urine samples were collected daily, with nine athletes developing respiratory pathologies (8 COVID-19, 1 bronchitis). Nuclear Magnetic Resonance spectroscopy was used to analyze the samples, followed by data processing with Principal Component Analysis (PCA) and Partial Least Squares Discriminant Analysis (PLS-DA), allowing to use Variable Importance in Projection (VIP) scores to identify key metabolites contributing to group separation. Results: The PLS-DA model for respiratory illness showed good performance (R2 = 0.89, Q2 = 0.35, p < 0.05). Models for altitude training achieved higher predictive power (Q2 = 0.51 and 0.72, respectively). Metabolites kynurenine, N-methylnicotinamide, pyroglutamate, propionate, N-formyltryptophan, tryptophan and glucose were significantly highlighted in case of respiratory illness while trigonelline, 3-hydroxyphenylacetate, glutamate, creatine, citrate, urea, o-hydroxyhippurate, creatinine, hippurate and alanine were correlated to effort in altitude. This distinction confirms that respiratory illness induces a unique metabolic profile, clearly separable from hypoxia and training-induced adaptations. Conclusions: This study highlights the utility of metabolomics in identifying biomarkers of respiratory pathologies in athletes during altitude training, offering the potential for improved monitoring and intervention strategies. These findings could enhance athlete health management, reducing the impact of illness on performance during critical training periods. Further research with larger cohorts is warranted to confirm these results and explore targeted interventions.

Editorial: The cognitive era in sports performance: mental fatigue, cognitive training, and psychological ergogenic substances

2025-06-17
Dalton de Lima‐Júnior , Thiago Ribeiro Lopes , Leonardo de Sousa Fortes +2 more | Frontiers in Psychology

Análisis de la supervivencia en un programa de trasplante pulmonar en alta altitud: conocimientos de un estudio observacional de la vida real

2025-06-17
Fabio Varón-Vega , Adriana Rincón , Eduardo Tuta-Quintero +3 more | Cirugía y Cirujanos

Chemistry vs. compensation: Comparing integrated respiratory-renal responses between acute inspired normobaric hypoxia vs. sustained hypobaric hypoxia

2025-06-17
Nicole Johnson , Nicholas D. J. Strzalkowski , Monica K. Russell +6 more | Journal of Applied Physiology
During acute exposure to hypoxia, peripheral respiratory chemoreceptors detect decreases in blood oxygenation, eliciting a hypoxic ventilatory response (HVR), which is enhanced with the duration and intensity of exposure (ventilatory … During acute exposure to hypoxia, peripheral respiratory chemoreceptors detect decreases in blood oxygenation, eliciting a hypoxic ventilatory response (HVR), which is enhanced with the duration and intensity of exposure (ventilatory acclimatization). The HVR protects oxygenation, but a secondary consequence is the elimination of PaCO 2 , resulting acutely in hypocapnia and respiratory alkalosis. With sustained exposure to hypobaric hypoxic conditions (e.g., high altitude ascent; HA), the renal tubules reduce HCO 3 - reabsorption and H+ excretion, excreting HCO 3 - and retaining H + , returning arterial pHa toward normal values. We aimed to characterize and compare blood oxygenation and acid-base homeostasis between two models of hypoxic exposure with matching P I O 2 (~74-76 mmHg): acute hypoxic exposure eliciting an HVR-mediated hypocapnia over 24-min vs. sustained hypoxic-hypocapnia with incremental ascent to HA over 10-days. Using arterial blood draws, we measured PaO 2 , SaO 2 , PaCO 2 , [HCO 3 − ]a and pHa, obtained before and following (a) acute stepwise reductions in FIO2 for ~24-min, with the last step being an F I O 2 of 0.12 (P I O 2 ≅74mmHg) and (b) sustained exposure to hypoxia during incremental ascent to 5,200m over 10-days (P I O 2 ≅76mmHg). We found that (a) acute normobaric hypoxia elicited hypocapnia and respiratory alkalosis, as expected, and (b) after sustained exposure to hypobaric hypoxia, there was persistent alkalosis, despite appreciable renal compensation. These findings highlight the time-course and magnitude of integrated respiratory responses and subsequent renal compensation mounted by the kidneys, specifically that the hypoxia-mediated hypocapnia and respiratory alkalosis experienced at 5,200m is likely beyond the threshold for a full renal compensation in healthy lowlanders.

Changes in Retinal Vasculature Phenotype and Choroidal Blood Flow at High Altitude in Healthy Lowlanders

2025-06-16
Jérémy De Abreu , Aymeric Paillisser , Florence Berquet +7 more | Investigative Ophthalmology & Visual Science
The aim of this study was to characterize changes in retinal vessel diameters and choroidal blood flow in healthy lowlanders during a high-altitude expedition. Ocular examination, fundus images acquired using … The aim of this study was to characterize changes in retinal vessel diameters and choroidal blood flow in healthy lowlanders during a high-altitude expedition. Ocular examination, fundus images acquired using a handheld camera, and laser Doppler flowmetry (LDF) measurements within the subfoveal choroid (blood flow = ChBF, blood velocity = ChVel, and blood volume = ChVol) were carried out at 200 m and after 9 days at 5100 m in 11 healthy participants. Fundus images were analyzed with the semi-automatic software Vessel Assessment and Measurement Platform for Images of the Retina (VAMPIRE) version 3.2 to quantify retinal vessel parameters: the central retinal artery equivalent (CRAE), the central retinal vein equivalent (CRVE), and arterial and venular tortuosity. Hematocrit and hemoglobin concentrations were also measured at both altitudes. Corneal thickness increased slightly at altitude (median = 536 µm, interquartile range = 25-75%: [521-571] at 200 m vs. 561 µm [540-574] at 5100 m, P = 0.004). No participant was affected by high-altitude retinopathy. From 200 m to 5100 m, ChVol and ChBF decreased significantly (-31% [43-22], P = 0.003 and -13% [22-8], P = 0.01, respectively), ChVel increased (+17% [10-44], P = 0.003), and CRVE (+10% [3-14], P = 0.04) and venular tortuosity (+142% [71-168], P = 0.04) increased significantly. The altitude-induced increase in hematocrit correlated negatively with the decrease in ChBF (r = -0.88, P < 0.001) and positively with the increase in CRVE (r = 0.88, P = 0.01). Acute high-altitude exposure leads to a decrease of ChBF (partly related to a decrease in blood volume) and an increase in retinal vein diameter and tortuosity. The physiological consequences of these changes on retinal blood flow and retinal function remain to be explored.

The role of heart rate variability in acute mountain sickness: A meta-analysis

2025-06-13
Tung‐Yao Tsai , Jun-Xian Lin , Ju‐Chi Ou +1 more | Medicine
Background: Acute mountain sickness (AMS) is associated with symptoms arising from an individual’s failure to acclimatize to high-altitude environments characterized by hypobaric hypoxia. Heart rate variability (HRV) has been proposed … Background: Acute mountain sickness (AMS) is associated with symptoms arising from an individual’s failure to acclimatize to high-altitude environments characterized by hypobaric hypoxia. Heart rate variability (HRV) has been proposed as a potential predictor of AMS, but results from individual studies have been inconsistent. Therefore, this study investigated HRV before and after ascent to provide a more comprehensive review of the relationship between HRV and AMS. Methods: We conducted a systematic search of MEDLINE, PubMed, and Google Scholar from inception to August 2023. Studies measuring HRV in relation to AMS were included. The quality of studies was assessed using the Newcastle–Ottawa scale. Results: Initially, 153 trials were identified through our search strategy. Seven studies met the inclusion criteria, comprising a total of 329 participants. Before ascent, individuals who developed AMS showed significantly higher percentage of successive R–R intervals that differ by more than 50 ms compared with those who did not develop AMS (standardized mean difference = 0.40, 95% confidence interval: [0.11 to 0.69]). After ascent, the AMS group exhibited significantly lower standard deviation of normal-to-normal R–R intervals (standardized mean difference = −0.41, 95% confidence interval: [−0.69 to −0.13]). Other HRV parameters, including low-frequency and high-frequency power, showed trends toward lower values in the AMS group but did not reach statistical significance. Conclusion: This meta-analysis proves that certain HRV parameters, particularly percentage of successive R–R intervals that differ by more than 50 ms before ascent and standard deviation of normal-to-normal R–R intervals after ascent, may be associated with AMS development. These findings suggest that HRV analysis could potentially be used as a tool for predicting and monitoring AMS. However, further research is needed to establish definitive clinical guidelines.

Mechanisms of ventilatory acclimatization to high altitude

2025-06-13
Martin Burtscher , Axel Kleinsasser , Johannes Burtscher +1 more | National Science Review

Impact of Living in a Mountain Environment on Health and Mortality: Insights from the Alpine Population in Northern Italy

2025-06-13
Essi Hantikainen , Nikola Đorđević , Daniel Neunhäeuserer +3 more | Gerontology
Introduction: Residing at moderate altitudes has been associated with various health benefits also affecting mortality risk. This study investigates life expectancy and disease-specific mortality rates among populations in the Italian … Introduction: Residing at moderate altitudes has been associated with various health benefits also affecting mortality risk. This study investigates life expectancy and disease-specific mortality rates among populations in the Italian Alps and in northern Italian lowland regions. Additionally, cardiometabolic health and serum metabolite concentrations of residents in an Alpine province across three distinct elevation zones (&lt;1,000 m, 1,000-1,500 m, and &gt;1,500 m above sea level) are studied. Methods: Data on life expectancy and mortality rate (per ten thousand) were retrieved from the ISTAT database for 6 provinces located in the Italian Alps and 6 provinces at sea level near the Alps. Using cross-sectional data from a sub-sample of the Cooperative Health Research in South Tyrol (CHRIS) study (n=6,292), we fitted multivariable adjusted logistic regression models to investigate associations between altitude and cardiometabolic health, determined by the Cumulative Illness Rating Scale. Moreover, associations between altitude and 175 serum metabolites were evaluated through linear regression models (n=1,447). Results: Population size and sex distribution were similar between provinces (p&gt;0.485). Life expectancy at 65 years differed between areas (20.8±0.4 vs 20.1±0.3, for Alps vs sea-level, respectively, p=0.026). Mortality rate for diseases of the circulatory system was lower in the Alps than at sea-level (35.3±5.7 vs. 44.5±6.8, respectively, p=0.026). No statistically significant differences were found for mortality (Alps vs. sea-level) from all causes (108.1±15.7 vs. 126.1±15.5, p=0.065), cerebrovascular diseases (8.4±2.5 vs. 12.6±3.1, p=0.065), endocrine, nutritional and metabolic diseases (3.6±1.0 vs. 5.0±1.0, p=0.065), neoplasms (31.1±4.7 vs. 34.3±2.4 p=0.394) and diseases of the respiratory system (8.3±1.7 vs. 8.8±1.7, p=0.589). In the CHRIS study sample, living at moderate vs. low altitude level was associated with lower odds of mild to severe conditions in the hypertension (OR:0.77; 95%CI: 0.62-0.96) and endocrine-metabolic domain (OR:0.77, 95%CI: 0.61-0.97). No differences in blood serum metabolic profiles were observed between people living at different altitude levels. Conclusions: Living in the Italian Alps seems to have a positive effect on life expectancy and mortality from certain diseases compared to living at sea level in northern Italy. Furthermore, living at moderate altitude conferred some cardiometabolic health benefits in the CHRIS study population, even after corrections for confounding factors. The metabolite profile in a sub-sample did, however, not reveal any significant differences between altitude levels.

Education and urbanization improves cognitive function affected by altitude of adolescents: a cross-section study in Tibet, China

2025-06-13
Yangzong Ciren , Jianhong Gong , Furong Li +6 more | Frontiers in Public Health
Background The aim of the study was to examine the cognitive function of Tibetan adolescents at different altitudes and evaluate the influence of education and urbanization on child’s cognition at … Background The aim of the study was to examine the cognitive function of Tibetan adolescents at different altitudes and evaluate the influence of education and urbanization on child’s cognition at high altitudes. Methods A cross-sectional study was conducted between October 2015 and September 2016 in four counties in Tibet. The study population included 324 adolescents living at an altitude of 2,800 m, including 227 who grew up at altitudes of 4,300 m, and 732 adolescents attending three high-altitude boarding schools (one at 4,300 m and two at 4,500 m), including 119 who grew up at an altitude of 2,800 m. Fluid reasoning was assessed using Standard Progressive Matrices (SPMs). The background information was collected using self-administered questionnaires. Results A multilevel linear regression model was used to determine the effects of altitude, education, and urbanization on fluid reasoning. In the fixed-effects model, the average SPM score of adolescents from low altitudes who attended kindergarten was 40.41. Scores of students who moved from high to low altitudes, came from high altitudes, and moved from low to high altitudes were 2.66, 4.71, and 6.70 points lower, respectively, than those of students from low altitudes, and 2.50 points lower in students who had not attended kindergarten than those who had. In the random-effects model, the scores of those who only went to first grade were 2.93 points lower. Students from County 3 had average scores of 1.89 higher than did students from the other three counties. Conclusion High altitudes may negatively affect the cognition of Tibetan adolescents. This effect was reduced by moving to a lower altitude, increasing the number of years of formal education, attending kindergarten, and living in a more urbanized location. Even at high altitude, moving to higher altitudes should be avoided.

Efficacy and safety of Rhodiola crenulata extract in the treatment of acute high altitude disease, based on studies involving populations in China: A systematic review and meta-analysis

2025-06-13
Zixuan Gao , Yaoyuan Liu , Wen-Jie Liao +6 more | Frontiers in Pharmacology
Introduction To evaluate the efficacy and safety of Rhodiola crenulata extract (RCE) for the treatment of patients with acute high altitude disease (AHAD). Methods This study systematically retrieved randomized controlled … Introduction To evaluate the efficacy and safety of Rhodiola crenulata extract (RCE) for the treatment of patients with acute high altitude disease (AHAD). Methods This study systematically retrieved randomized controlled trials (RCTs) published prior to September 2024 from eight distinct databases. It included AHAD patients, with the control group receiving either conventional western medicine (WM) or placebo, and the experimental group receiving RCE alone or in conjunction with WM. The primary outcomes were arterial oxygen saturation (SaO 2 ) and arterial partial pressure of oxygen (PaO 2 ). The secondary outcomes were total clinical efficacy, systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate (HR). Adverse events incidence was analyzed to assess safety. The meta-analysis was performed with Review Manager 5.4, and the evidence’s certainty was assessed using the GRADE approach. Results This study included 19 eligible RCTs with 1,690 participants. In improving SaO 2 , PaO 2 and total clinical efficacy, no significant differences were found between RCE and WM, but RCE was more effective than placebo. RCE showed no significant effect in reducing SBP, DBP and HR. Regarding safety, the experimental group demonstrated superior performance compared to the control group. Conclusion RCE may enhance blood oxygen levels and mitigate clinical symptoms in the treatment of AHAD with favorable safety. Nonetheless, it is imperative to undertake further rigorous RCTs to validate these findings. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/myprospero , identifier CRD42024593081.

Exogenous Ketosis during Early Acclimatization at High Altitude: Ventilatory, Cardiovascular and Muscular Responses to Maximal Exercise

2025-06-13
Domen Tominec , Myrthe Stalmans , Benjamin J. Narang +3 more | Medicine & Science in Sports & Exercise
ABSTRACT Background Exogenous ketosis, induced via ketone monoester (KE) ingestion, can attenuate blood desaturation and muscle deoxygenation during hypoxic exercise. However, its effect(s) on exercise capacity and underlying integrated physiological … ABSTRACT Background Exogenous ketosis, induced via ketone monoester (KE) ingestion, can attenuate blood desaturation and muscle deoxygenation during hypoxic exercise. However, its effect(s) on exercise capacity and underlying integrated physiological responses to incremental exercise to exhaustion during early acclimatization at terrestrial high altitude remain unexplored. Methods Healthy active adults were randomised to an intermittent exogenous ketosis (IEK; n = 16) or placebo (PLA, n = 17) group, before performing two incremental cycling tests to volitional exhaustion. The first was conducted at sea level (295 m) without prior supplementation. The second was conducted at high altitude (3375 m) following ~69 hours of acclimatization, during which participants intermittently ingested KE (IEK) or placebo (PLA). During exercise, gas exchange, cardiac output, and both blood and muscle oxygenation were recorded continuously using a metabolic cart, transthoracic impedance, earlobe oximetry and near-infrared spectroscopy, respectively. Results Pre-exercise blood ketone concentrations were higher in IEK than PLA (~2.1 mM vs . ~0.3 mM, P &lt; 0.001). However, both experimental groups exhibited comparable ( P = 0.525–0.644) high altitude-induced reductions in peak power output ( P &lt; 0.001), as well as in blood ( P &lt; 0.001) and muscle oxygenation ( P &lt; 0.001) during maximal exercise and submaximal power levels. Furthermore, high altitude significantly increased resting and/or exercising ventilation ( P &lt; 0.001) and cardiac output ( P &lt; 0.001), yet irrespective of the KE vs . placebo ingestion ( P = 0.529–0.828). Conclusions These findings indicate that intermittent exogenous ketosis during early acclimatization does not mitigate altitude- and exercise-induced reductions in blood and muscle oxygenation. Moreover, it does not importantly modulate ventilatory and cardiac output responses, and therefore does not seem to confer ergogenic advantage during subacute high altitude exposures.

Graduate Medical Education Fellowships Versus Specialty Society Curriculum: A Comparative Study on Alumni Outcomes and Academic Pursuits in Wilderness Medicine

2025-06-12
Stephanie Lareau , Pavel Diaz , Alec M. Chan‐Golston +1 more | Wilderness and Environmental Medicine

Lack of Altitude Medicine Knowledge Among Mountaineers in the Italian Alps

2025-06-05
Remco R. Berendsen , Dirk C.A.A. de Vries , Alea Steger +5 more | High Altitude Medicine & Biology
Berendsen, Remco R., Dirk C A.A. de Vries, Alea Steger, Nadine Herold, Feico J.J. Halbertsma, Adriaan F. Norbart, Hannes Gatterer, and Bengt Kayser. Lack of altitude medicine knowledge among mountaineers … Berendsen, Remco R., Dirk C A.A. de Vries, Alea Steger, Nadine Herold, Feico J.J. Halbertsma, Adriaan F. Norbart, Hannes Gatterer, and Bengt Kayser. Lack of altitude medicine knowledge among mountaineers in the Italian Alps. High Alt Med Biol. 00:00-00, 2025. Introduction: In 2022, expert consensus defined a set of minimum altitude medicine knowledge statements for laypersons traveling to high altitudes (STAK: strengthening altitude knowledge). We used these statements to assess knowledge among mountaineers in the Italian Alps. Methods: Mountaineers in a hut (3,647 m) completed an online STAK-based questionnaire, also indicating their confidence after each answer. A score of ≥19/28 was used as a statistical threshold, exceeding chance alone. Logistic regression assessed the link between confidence and correctness; multivariate regression explored demographic, educational, and behavioral predictors of achieving an above-threshold score. Results: Of 576 participants, 412 (72%) were included in the final analysis and 115 (28%) scored ≥19. Among them, 59% of medical professionals, 36% of mountain guides, and 23% of general participants reached the threshold; the medical professionals scored significantly higher than the general participants (p < 0.001). Both being a mountain guide (odds ratios [OR]: 2.3, 95% confidence intervals [CI]: 1.0-5.0, p < 0.05) and being a medical professional (OR: 4.5, 95% CI: 2.1-10.0, p < 0.001) were associated with higher scores. Conclusion: Using STAK as a benchmark, we found a substantial lack of altitude medicine knowledge in mountaineers, even among guides and medical professionals. These findings suggest a potential for targeted educational interventions.

The effect of hypoxia on rheumatoid arthritis

2025-06-02
Anting Liu , Shuang Li , Chenlu Huo +3 more | Modern Rheumatology
Abstract Rheumatoid arthritis (RA) is a chronic autoimmune disease with synovitis as the main pathologic change, and acute exacerbation severely affects patients’ quality of life, but its specific pathogenesis has … Abstract Rheumatoid arthritis (RA) is a chronic autoimmune disease with synovitis as the main pathologic change, and acute exacerbation severely affects patients’ quality of life, but its specific pathogenesis has not been clarified. The effects of low-pressure hypoxia brought on by high-altitude surroundings and intestinal hypoxia have received comparatively less attention, even though hypoxia is a distinct state in the synovium of RA. In an effort to offer fresh approaches and ideas for treating RA, reducing pain, and enhancing quality of life, this review updates the mechanism of synovial hypoxia on RA in recent years. It also advances the theory that intestinal hypoxia and low-pressure hypoxia in the external environment also aggravate arthritis.

Aerobic Intermittent Hypoxic Training Is Not Beneficial for Maximal Oxygen Uptake and Performance: A Systematic Review and Meta‐Analysis

2025-06-01
Gianluigi Dorelli , Gaia Giuriato , G.A. Zamboni +7 more | Scandinavian Journal of Medicine and Science in Sports
ABSTRACT Although many studies have investigated whether aerobic training in hypoxia (IHT) could bring advantages to maximal oxygen uptake (V̇O 2max ) and sea‐level performance when compared to analogous normoxic … ABSTRACT Although many studies have investigated whether aerobic training in hypoxia (IHT) could bring advantages to maximal oxygen uptake (V̇O 2max ) and sea‐level performance when compared to analogous normoxic training (NT), the literature results are inconsistent. This variability may come from differences in population, training protocols, hypoxic methods, and potential bias. Therefore, a comprehensive meta‐analysis with strict inclusion criteria is needed to assess the effects of aerobic IHT on V̇O 2max and performance. This study aims to review previous meta‐analyses and analyze all parallel‐design studies examining the effect of aerobic IHT compared to NT on V̇O 2max and sea‐level aerobic performance. Systematic research was conducted following PRISMA guidelines regarding the effects of aerobic IHT on sea‐level V̇O 2max and performance outcomes. The analysis accounted for characteristics of the population, training protocol, hypoxic environment, and publication details. A total of 35 studies involving 524 participants were included. The analysis showed that IHT, compared to NT, did not significantly improve V̇O 2max ( p = 0.333), peak power output ( p = 0.159), and time to exhaustion ( p = 0.410). Subgroup analyses identified no significant differences based on fitness level ( p = 0.690) and exercise modality ( p = 0.900); however, a publication bias was found ( p = 0.004). These results suggest that, despite some enthusiastic findings in the literature, possibly influenced by publication‐related biases, aerobic IHT does not offer superior improvement in V̇O 2max and performance compared with NT. Therefore, adding hypoxia to aerobic exercise does not enhance training adaptations.

Inhibition of ER stress mitigates hypobaric hypoxia-induced retinal damage: a simulated high-altitude study

2025-06-01
Xiang‐Jun Zheng , Cong Han , Yi Yang +1 more | Neuroscience

Recommendations for mountain travel and altitude acclimation in pediatric populations: a French Delphi study

2025-06-01
Clémence Rascle , Pauline Connan , Corentin Tanné | Archives de Pédiatrie