Pulmonary Function Differences Between Sherpas and Acclimatized Lowlanders at Altitude

Tibetans have higher resting ventilation and arterial oxygen saturation, less excessive polycythemia and lower pulmonary artery pressures than other high altitude populations. Faoro et al (2013) compared pulmonary indices between 13 Sherpas and 13 acclimatized lowlander controls at 5050 m altitude. Compared to lowlanders, Sherpa SpO₂ was 86 vs 83%, (NS), mean resting pulmonary arterial pressure 19 vs 23 mmHg (p<0.05), DLCO corrected for Hgb was 61 vs 37 ml^.min^−1.mmHg⁻¹ (p<0.001), DLNO was 226 vs 153 ml^.min^−1.mmHg⁻¹ (p<0.001), maximum oxygen uptake (VO_2max) was 32 vs 28 ml^.kg^−1.min⁻¹ (NS) and ventilatory equivalent for carbon dioxide at anaerobic threshold was 40 vs 48 (p<0.001). The authors conclude that Sherpas have less pulmonary hypertension, lower ventilatory responses to work and higher lung diffusing capacity although they do not have significantly greater aerobic exercise capacity.

Acclimatization to High Altitude Reduces Central but not Peripheral Fatigue in Hypoxic Exercise

The development of muscle fatigue is O₂-delivery sensitive. Exercise during acute hypoxia increases inspiratory muscle work, also limiting O₂ -delivery. Since chronic hypoxia (CH) partially normalizes arterial O₂ content but exacerbates the work of breathing, Amann et al (2013) compared central and peripheral fatigue before and after 14 days at 5260 m altitude in 8 subjects using constant-load cycling exercise. Peripheral fatigue was expressed as pre-exercose to post-exercise percent reduction in electrically-evoked quadriceps twitch-force. Central fatigue was expressed as the exercise-induced percent decrease in voluntary muscle activation. After 14 days acclimatization, peripheral fatigue was similar but central fatigue was less.

Cerebral Blood Flow (CBF) During Two Weeks at 5050 m Altitude

Adding to the many prior CBF studies of humans during acclimatization, Willie et al (2013) found a progressive rise over the first 3 days to a peak 53% above control, followed by fall to about +15% at 1 and +12% at 2 weeks. SpO₂ remained about 80% and P_etCO₂ remained at about 30 torr over 2 weeks at 5050 m refuting the conclusion that rising SpO2 explained (even in part) the gradual fall of CBF from its peak to a plateau that had been reported in many prior studies.

Acclimatization Improves Submaximal Exercise Economy at 5533 m Altitude

During an expedition to Mt. Muztagh Ata, Latshang et al (2013) report that 32 mountaineers, repeatedly tested with progressive bicycle exercise to exhaustion, showed 9% improved net efficiency between the 6^th and 11^th days at 5533 m while SaO₂ rose from 68% to 74%. As expected, maximal work rate decreased 46% from 490 m. Ratios of VO₂ to work rate increments remained unchanged. On day 11, mountaineers climbed faster from 4497 m to 5533 m than on days 5–6 but perceived less effort (VA scale) and noted reduced symptoms of acute mountain sickness. The authors conclude that the better performance and subjective exercise tolerance after acclimatization were related to regression of acute mountain sickness and improved submaximal exercise economy because of lower metabolic demands for non-external work-performing functions. The authors do not imply inherent improved working muscle efficiency.

Comparing Pathologic Effects of Normobaric vs Hypobaric Hypoxia

Richard et al (2013) confirm that pathophysiologic and physiologic effects of equivalent PO₂ exposures during moderate acute hypoxemia are independent of total pressure in humans. In 11 volunteers they tested hypercapnic and hypoxic ventilatory responses, Lake Louise scores, SpO₂ and blood pressure on two occasions using either Pb=427 torr with 21% O₂ or 760 torr with 10.5% O₂. No differences were seen indicating any total pressure effects.

Moderate Exercise Reduces Oxidative Stress During Hypoxia

Debevec et al (2013) tested 14 males during 10 days in normobaric hypoxia (4000 m simulated altitude). Eight exercised twice daily at 50% of hypoxic maximal aerobic power. Nine plasma indicators of oxidative stress were measured before, during and after the study. Advanced oxidation protein products and nitrotyrosine were higher without exercise. Exercising subjects had increased SOD and catalase indicating that two hours of moderate daily exercise training can attenuate the oxidative stress induced by continuous hypoxic exposure.

A Single Dose of Beetroot Juice Enhances Cycling Performance in Simulated Altitude

Increasing nitric oxide bioavailability via supplementation with nitrate-rich beetroot juice has been shown to attenuate the negative impact of hypoxia on peripheral oxygen saturation and exercise tolerance. In 16.1 km timed trials during acute hypoxia equivalent to 2500 m altitude, 3 hr after taking 70 mL of concentrated beetroot juice, Muggeridge et al (2013) report a 2.5% time reduction (p=0.021) in 9 trained cyclists. Prior to testing, beetroot increased plasma nitrate from ∼40 to ∼150 mμM and nitrite from ∼300 to ∼700 nM. VO₂ during steady-state exercise was 7% lower with beetroot (p=0.049).

Peruvian Altiplano Dwellers Improve Health by Use of Maca (Lepidium meyenii)

Lepidium meyenii (Maca) is an altiplano plant, the hypocotyls of which are traditionally consumed for their nutritional and medicinal properties. Gonzales, Gasco and Lozada-Requena (2013) determined the health status based on a health related quality of life questionnaire, a leg muscle time test and serum levels of interleukin 6 (IL-6) in 27 consumers and 23 non-consumers living at 4,100 m. Users had a lower CMS score (chronic mountain sickness, primarily based on Hct), a higher health status score (p<0.01), better leg muscle performance time test (p<0.01), and lower serum IL-6 (p<0.05). No negative influences were identified.

Acute Hypoxia Shifts Brain White Matter Water into Extracellular Spaces

Lawley et al (2013) examined MRI indices of brain white matter water mobility in 13 normal subjects after 2 and 10 hours breathing 12% O₂. Mean diffusivity was reduced in the left posterior hemisphere after 2 hours and throughout cerebral white matter after 10 hours with no changes in T2 relaxation time or fractional anisotropy. Changes correlated with headache score after 10 hours. The authors conclude that acute hypoxia caused a shift of water into the intracellular space within the cerebral white matter without edema (volumetric enlargement).

Genetic Differences in Japanese Volunteers Susceptible to High Altitude Pulmonary Edema (HAPE)

Using genome-wide association analysis, Kobayashi et al (2013) compared 53 subjects susceptible to HAPE (HAPE-s) and 67 elite Alpinists resistant to HAPE (HAPE-r). Allele frequencies in nine markers were statistically different between HAPE-s and HAPE-r subjects. The SNP genotyping of the TIMP3 gene revealed that the derived allele C of rs130293 and haplotype CAC carrying allele C of rs130293 were associated with resistance to HAPE P=0.0012) while the ancestral allele T was associated with susceptibility to HAPE (p=0.0012).

Genetic Abnormalities in Chronic Mountain Sickness in Andean Highlanders

Chronic mountain sickness, now preferably termed chronic mountain polycythemia, is fairly common in humans living over 3500 m altitude (particularly in the Andes). Zhao et al (2013) sequenced and compared the whole genomes of 20 altiplano natives, 10 with CMS and 10 without. They report 11 genome-wide regions with significant differences in haplotype frequencies consistent with selective sweeps. Two genes (an erythropoiesis regulator, SENP1, and an oncogene, ANP32D) were 2 and 4 fold (resp) above normal in individuals with CMS and well below controls in the highlanders without CMS.

Changes in Human Plasma Proteome on Adaptation to Hypobaric Hypoxia

Ahmad et al (2013) compared, by proteomic analysis, plasma proteins from 10 high altitude natives and 10 sea level natives after removing the two abundant proteins, albumin and IgG. In high altitude natives, the up-regulated proteins were vitamin D-binding protein, hemopexin, alpha-1-antitrypsin, haptoglobin beta-chain, apolipoprotein A1, transthyretin and hemoglobin beta chain. The down-regulated proteins were transferrin, complement C3, serum amyloid, complement component 4A and plasma retinol binding protein. These proteins that differ at altitude all play a positive anti-inflammatory role. The results suggest some adaptive mechanism that sustains the inflammation balance in high altitude natives exposed to hypobaric hypoxia.

Iron Transport and Metabolism in Acute High Altitude Exposure

Human iron homeostasis is regulated by intestinal iron transport, hepatic hepcidin release and signals from pathways that consume or supply iron. Goetze et al (2013) examined the effect in 25 healthy mountaineers of 4 days at 4559 m altitude on serum iron, hepatic hepcidin release, intestinal iron transport, and systemic inflammatory and erythropoietic responses using duodenal biopsies. Serum iron and ferritin levels declined rapidly at altitude and in response duodenal divalent metal-ion transporter 1 and ferroportin 1 mRNA rapidly increased up to 10-fold and protein expression increased. Serum hepcidin levels decreased. Erythropoietin and growth differentiation factor 15 peaked on day 2. IL-6 only increased on day 2. The authors conclude that, under hypoxemic conditions, hepcidin is repressed and duodenal iron transport is rapidly up regulated. These changes may increase dietary iron uptake and allow release of stored iron to ensure a sufficient iron supply for hypoxia induced compensatory erythropoiesis.

Rat Memory EPO Recovery Better with Enriched Environment After 8,000 m Injury

After global cerebral hypoxia, many patients are severely disabled even after intensive neuro-rehabilitation. Secondary mechanisms of brain injury as a result of biochemical and physiological events occur within a period of hours to months, and provide a window of opportunity for therapeutic intervention. Erythropoietin (EPO) has been shown to be neuro-protective in the brain subjected to a variety of injuries. Hralova et al (2013) exposed 59 male rats to hypobaric hypoxia simulating an altitude of 8000 m. One half of the animals received erythropoietin injections. Exposure to a Morris water maze disclosed better spatial learning only in the group that had EPO and an enriched environment.

Fetal Circulation and Body Fat are not Abnormal During Gestation at 3100 m Altitude

While birth weight is reduced at high altitude, fetal circulation and fat alterations are not known to be different at altitude. 24 Leadville pregnant primiparas (3,100 m) were compared to 18 Denver controls during 20 to 36 weeks gestation. Fetal biometry was used to obtain axial images for assessing mid-upper arm and mid-thigh subcutaneous tissue mass. Doppler waveform analysis measured indices of vascular function in the fetal umbilical arteries, umbilical vein, middle cerebral artery, and ductus venosus. No significant differences between altitudes were found (except lower weight) (Schwartz et al., 2013).

Data on Probability of Decompression Sickness

Conkin et al (2013) provide data on probability of bends from 29 tests using 708 human altitude chamber exposures to direct ascent at 1524 m^.min⁻¹ to 226 to 378 mmHg for 4 h with a variety of oxygen pre-breathing times and with varying degrees of physical activity while at altitude. Three predictors (decompression dose, male gender and higher exercise intensity) increased the probability of getting bends.