Change in plasma amino acid concentrations during breath-hold diving at high altitude

We studied the plasma concentration of various amino acids in 6 Italian sport divers in Italy and at approximately 4,500 m altitude in Peru; 6 Peruvian inhabitants were examined for comparison. We attempted to create a situation of pronounced hypoxia in muscles by breath-hold diving at altitude. The diving reflex diverts blood away from muscles while diving increases central oxygen tension and prevents loss of consciousness. Differences in certain amino acids, probably related to diet, were noted between Italy and Peru. Increases in concentration of plasma alanine and some branched-chain amino acids occurred after breath-hold diving. These changes were similar to those seen after prolonged hard exercise, even though physical work was low. Hypoxia in muscles, common during hard work and during breath-hold diving at altitude, might thus be the stimulus for amino acid release from working muscles.     

Role of the altitude level on cerebral autoregulation in residents at high altitude.

Cerebral autoregulation is impaired in Himalayan high-altitude residents who live above 4,200 m. This study was undertaken to determine the altitude at which this impairment of autoregulation occurs. A second aim of the study was to test the hypothesis that administration of oxygen can reverse this impairment in autoregulation at high altitudes. In four groups of 10 Himalayan high-altitude dwellers residing at 1,330, 2,650, 3,440, and 4,243 m, arterial oxygen saturation (Sa(O(2))), blood pressure, and middle cerebral artery blood velocity were monitored during infusion of phenylephrine to determine static cerebral autoregulation. On the basis of these measurements, the cerebral autoregulation index (AI) was calculated. Normally, AI is between zero and 1. AI of 0 implies absent autoregulation, and AI of 1 implies intact autoregulation. At 1,330 m (Sa(O(2)) = 97%), 2,650 m (Sa(O(2)) = 96%), and 3,440 m (Sa(O(2)) = 93%), AI values (mean +/- SD) were, respectively, 0.63 +/- 0.27, 0.57 +/- 0.22, and 0.57 +/- 0.15. At 4,243 m (Sa(O(2)) = 88%), AI was 0.22 +/- 0.18 (P < 0.0005, compared with AI at the lower altitudes) and increased to 0.49 +/- 0.23 (P = 0.008, paired t-test) when oxygen was administered (Sa(O(2)) = 98%). In conclusion, high-altitude residents living at 4,243 m have almost total loss of cerebral autoregulation, which improved during oxygen administration. Those people living at 3,440 m and lower have still functioning cerebral autoregulation. This study showed that the altitude region between 3,440 and 4,243 m, marked by Sa(O(2)) in the high-altitude dwellers of 93% and 88%, is a transitional zone, above which cerebral autoregulation becomes critically impaired.     

Responses of the autonomic nervous system in altitude adapted and high altitude pulmonary oedema subjects

Studies were carried out to ascertain the role of sympatho-parasympathetic responses in the process of adaptation to altitude. The assessment of status of autonomic balance was carried out in a group of 20 young male subjects by recording their resting heart rate, blood pressure, oral temperature, mean skin temperature, extremity temperatures, pupillary diameter, cold pressor response, oxygen consumption, cardioacceleration during orthostasis and urinary excretion of catecholamines; in a thermoneutral laboratory. The same parameters were repeated on day 3 and at weekly intervals for a period of 3 weeks, after exposing them to 3,500 m; and also after return to sea level. At altitude, similar studies were carried out in a group of 10 acclimatized lowlanders, 10 high altitude natives and 6 patients who had recently recovered from high altitude pulmonary oedema. In another phase, similar studies were done in two groups of subjects, one representing 15 subjects who had stayed at altitude (3,500–4,000 m) without any ill effects and the other comprising of 10 subjects who had either suffered from high altitude pulmonary oedema (HAPO) or acute mountain sickness (AMS). The results revealed sympathetic overactivity on acute induction to altitude which showed gradual recovery on prolonged stay, the high altitude natives had preponderance to parasympathetic system. Sympathetic preponderance may not be an essential etiological factor for the causation of maladaptation syndromes.     

Genetic adaptation to high altitude in the Ethiopian highlands

Background

Genomic analysis of high-altitude populations residing in the Andes and Tibet has revealed several candidate loci for involvement in high-altitude adaptation, a subset of which have also been shown to be associated with hemoglobin levels, including EPAS1, EGLN1, and PPARA, which play a role in the HIF-1 pathway. Here, we have extended this work to high- and low-altitude populations living in Ethiopia, for which we have measured hemoglobin levels. We genotyped the Illumina 1M SNP array and employed several genome-wide scans for selection and targeted association with hemoglobin levels to identify genes that play a role in adaptation to high altitude.

Results

We have identified a set of candidate genes for positive selection in our high-altitude population sample, demonstrated significantly different hemoglobin levels between high- and low-altitude Ethiopians and have identified a subset of candidate genes for selection, several of which also show suggestive associations with hemoglobin levels.

Conclusions

We highlight several candidate genes for involvement in high-altitude adaptation in Ethiopia, including CBARA1, VAV3, ARNT2 and THRB. Although most of these genes have not been identified in previous studies of high-altitude Tibetan or Andean population samples, two of these genes (THRB and ARNT2) play a role in the HIF-1 pathway, a pathway implicated in previous work reported in Tibetan and Andean studies. These combined results suggest that adaptation to high altitude arose independently due to convergent evolution in high-altitude Amhara populations in Ethiopia.     

Mast cells in the human lung at high altitude

Mast cell densities in the lung were measured in five native highlanders of La Paz (3600 m) and in one lowlander dying from high-altitude pulmonary oedema (HAPO) at 3440 m. Two of the highlanders were mestizos with normal pulmonary arteries and the others were Aymara Indians with muscular remodelling of their pulmonary vasculature. The aim of the investigation was to determine if accumulation of mast cells in the lung at high altitude (HA) is related to alveolar hypoxia alone, to a combination of hypoxia and muscularization of the pulmonary arterial tree, or to oedema of the lung. The lungs of four lowlanders were used as normoxic controls. The results showed that the mast cell density of the two Mestizos was in the normal range of lowlanders (0.6–8.8 cells/mm²). In the Aymara Indians the mast cell counts were raised (25.6–26.0 cells/mm²). In the lowlander dying from HAPO the mast cell count was greatly raised to 70.1 cells/mm² lung tissue. The results show that in native highlanders an accumulation of mast cells in the lung is not related to hypoxia alone but to a combination of hypoxia and muscular remodelling of the pulmonary arteries. However, the most potent cause of increased mast cell density in the lung at high altitude appears to be high-altitude pulmonary oedema.     

Effect of high altitude hypoxia on the human EEG

The paper presents the results of the comparative study of the EEG at alpine altitudes (Tuya -- Ashu pass, 3200 m) and at low altitudes (City of Frunze, 760 m above the sea level). The dynamics of EEG changes at different stages of adaptation to hypoxia is also traced. The obtained data show that the alpine hypoxia produces a considerable intensification of the excitation processes in the cerebral cortex. Different sensitivity to the oxigen shortage has been found in the frontal-temporal parts of the right and the left hemispheres.     

氧化应激在高原重体力劳动过程中急性高原反应发生中的作用

目的：观察氧化应激在高原重体力劳动过程中急性高原反应（AHAR）发生中的作用。方法：由低海拔（1500m）快速进入高原（3700m）并从事重体力劳动的男性官兵96名,年龄18～35岁。根据AHAR症状评分,分为重度AHAR组（A组,n=24）、轻中度AHAR组（B组,n=47）和无AHAR组（C组,n=25）,在该高度逗留50d后下撤前及返回低海拔（1500m）后12h、15d分别测定血清8．异前列腺素F2a（8-iso-PGF2a）、超氧化物歧化酶（SOD）、丙二醛（MDA）,并与低海拔（1500m）50名健康官兵（D组）比较。结果：A组血清8-iso-PGF2a、MDA[分别为（9．53±0．47）μg／L、（8．91±0．39）μmol／L]水平显著高于B组[分别为（8．34±O．42）μg／L、（7．31±0．32）μmol／L]、C组[分别为（7．02±0．48）μg／L、（6．41±0．23）μmol／L和D组[分别为（5．13±0．56）μg／L、（5．48±0．33）μmol／L]（均P〈0．01）,SOD（52．08±3．44）μ／mL水平显著低于B组（62．27±2．54）μ/mL、C组（71．99±3．35）μ/mL和D组（80．78±3．44）μ/mL,（均P〈0．01）,B组与c组之间和C组与D组之间亦有显著性差异（均P〈0．01）。海拔3700mAHAR总计分与血清8-iso-PGF2α、ⅣⅡ）A呈显著正相关（均P〈0．01）,与血清SOD显著负相关（P〈0．01）;8-iso-PGF2α、MDA与SOD显著负相关（均P〈0．01）。海拔3700m50d,血清8-iso-PGF2α、MDA水平显著高于,SOD水平显著低于海拔1500m12h、15d和D组（均P〈0．01）,海拔1500m12h与15d之间有显著性差异（均P〈0．01）,海拔1500m 15d与D组之间无显著性差异。结论：人体在高原低氧并重体力时氧化应激和氧化．抗氧化失衡与AHAR的发病和程度有密切关系,氧化应激和氧化．抗氧化失衡越严重,AHAR越重。返回低海拔后12h有显著改善,15d恢复到正常水平。     

Evolution of muscle phenotype for extreme high altitude flight in the bar-headed goose

Bar-headed geese migrate over the Himalayas at up to 9000 m elevation, but it is unclear how they sustain the high metabolic rates needed for flight in the severe hypoxia at these altitudes. To better understand the basis for this physiological feat, we compared the flight muscle phenotype of bar-headed geese with that of low altitude birds (barnacle geese, pink-footed geese, greylag geese and mallard ducks). Bar-headed goose muscle had a higher proportion of oxidative fibres. This increased muscle aerobic capacity, because the mitochondrial volume densities of each fibre type were similar between species. However, bar-headed geese had more capillaries per muscle fibre than expected from this increase in aerobic capacity, as well as higher capillary densities and more homogeneous capillary spacing. Their mitochondria were also redistributed towards the subsarcolemma (cell membrane) and adjacent to capillaries. These alterations should improve O₂ diffusion capacity from the blood and reduce intracellular O₂ diffusion distances, respectively. The unique differences in bar-headed geese were much greater than the minor variation between low altitude species and existed without prior exercise or hypoxia exposure, and the correlation of these traits to flight altitude was independent of phylogeny. In contrast, isolated mitochondria had similar respiratory capacities, O₂ kinetics and phosphorylation efficiencies across species. Bar-headed geese have therefore evolved for exercise in hypoxia by enhancing the O₂ supply to flight muscle.     

Genes for the high life: New genetic variants point to positive selection for high altitude hypoxia in Tibetans

People living on the high plateaus of the world have long fascinated biological anthropologists and geneticists because they live in "thin air" and epitomize an extreme of human biological adaptation.Far from posing obstacles to human habitation,the hypoxic conditions of the Tibetan Plateau,the Andean highlands,and the Amhara Plateau of Ethiopia have served as the contexts for natural experiments in human adaptability (Beall,2014).To the studies of the high-altitude human phenotype of the latter half of the twentieth century have been added studies of the complementary high-altitude genotype in the first decades of the twenty first century.     

Morphological characteristics of the pituitary-gonad system in high altitude hypoxia

The experiments on male rats showed that their sojourn at high altitude resulted in alterations of functional relationship between the gonadotropic pituitary cells and tests. That was characterized by synthesis inhibition and hormone release by gonadotropocytes. In the testes we found impairments in the barrier function and active substance transport in sustentocytes. Intensification of destructive processes in sustentocytes, with prolongation of adaptation duration, are mediated to a greater extent by a direct destructive high altitude factors. A decrease in hormone producing function of glandulocytes as a result of destruction processes has aggravated dysharmony of the pituitary-testes system which by the end of the second month was manifested by a marked inhibition of gonadotropic cell hormone release with preservation of the synthesis high level in them.