High-altitude Residents Research Articles

Altered placental ion channel gene expression in preeclamptic high-altitude pregnancies.

High-altitude (>2,500 m) residence increases the risk of pregnancy vascular disorders such as fetal growth restriction and preeclampsia, each characterized by impaired placental function. Genetic attributes of highland ancestry confer relative protection against vascular disorders of pregnancy at high altitudes. Although ion channels have been implicated in placental function regulation, neither their expression in high-altitude placentas nor their relationship to high-altitude preeclampsia has been determined. Here, we measured the expression of 26 ion-channel genes in placentas from preeclampsia cases and normotensive controls in La Paz, Bolivia (3,850 m). In addition, we correlated gene transcription to maternal and infant ancestry proportions. Gene expression was assessed by PCR, genetic ancestry evaluated by ADMIXTURE, and ion channel proteins localized by immunofluorescence. In preeclamptic placentas, 11 genes were downregulated (ABCC9, ATP2A2, CACNA1C, KCNE1, KCNJ8, KCNK3, KCNMA1, KCNQ1, KCNQ4, PKD2, and TRPV6) and two were upregulated (KCNQ3 and SCNN1G). KCNE1 expression was positively correlated with high-altitude Amerindian ancestry and negatively correlated with non-high altitude. SCNN1G was negatively correlated with African ancestry, despite minimal African admixture. Most ion channels were localized in syncytiotrophoblasts (Cav1.2, TRPP2, TRPV6, and Kv7.1), whereas expression of Kv7.4 was primarily in microvillous membranes, Kir6.1 in chorionic plate and fetal vessels, and MinK in stromal cells. Our findings suggest a role for differential placental ion channel expression in the development of preeclampsia. Functional studies are needed to determine processes affected by these ion channels in the placenta and whether therapies directed at modulating their activity could influence the onset or severity of preeclampsia.

Risk factors for microalbuminuria in adult Tibetan patients with high-altitude pulmonary hypertension: a cross-sectional study.

It has been suggested that chronic hypoxia underlies the higher prevalence of microalbuminuria in high-altitude residents than in sea-level dwellers. This study explored the risk factors for microalbuminuria in Tibetans with high-altitude pulmonary hypertension (HAPH). This retrospective cross-sectional study included adult patients with HAPH admitted to the People's Hospital of Tibet Autonomous Region between November 2018 and August 2019. One hundred and twenty patients with HAPH were included in this study, and 69 patients (57.5%) had microalbuminuria. Compared with the patients without microalbuminuria, the microalbuminuria group had significantly higher values for age, pulmonary arterial systolic pressure (PASP), systolic blood pressure, diastolic blood pressure, blood hemoglobin concentration, glycated hemoglobin, serum creatinine, and serum uric acid, significantly lower values for heart rate, peripheral oxygen saturation (SpO2), estimated glomerular filtration rate, and 6-min walking distance, and poorer New York Heart Association functional class (P<0.05 for all variables). PASP [odds ratio (OR): 1.55; 95% CI: 1.19-2.00; P=0.001] and SpO2 (OR = 0.78; 95% CI: 0.63-0.97; P=0.02) were independently associated with microalbuminuria. Higher PASP and lower SpO2 were independently associated with microalbuminuria in adult Tibetan patients with HAPH.

The Increase in Hemoglobin Concentration With Altitude Differs Between World Regions and Is Less in Children Than in Adults.

To compensate for decreased oxygen partial pressure, high-altitude residents increase hemoglobin concentrations [Hb]. The elevation varies between world regions, posing problems in defining cutoff values for anemia or polycythemia. The currently used altitude adjustments (World Health Organization [WHO]), however, do not account for regional differences. Data from The Demographic and Health Survey (DHS) Program were analyzed from 32 countries harboring >4% of residents at altitudes above 1000 m. [Hb]-increase, (ΔHb/km altitude) was calculated by linear regression analysis. Tables show 95% reference intervals (RIs) for different altitude ranges, world regions, and age groups. The prevalence of anemia and polycythemia was calculated using regressions in comparison to WHO adjustments. The most pronounced Δ[Hb]/km was found in East Africans and South Americans while [Hb] increased least in South/South-East Asia. In African regions and Middle East, [Hb] was decreased in some altitude regions showing inconsistent changes in different age groups. Of note, in all regions, the Δ[Hb]/km was lower in children than in adults, and in the Middle East, it was even negative. Overall, the Δ[Hb]/km from our analysis differed from the region-independent adjustments currently suggested by the WHO resulting in a lower anemia prevalence at very high altitudes. The distinct patterns of Δ[Hb] with altitude in residents from different world regions imply that one single, region-independent correction factor for altitude is not be applicable for diagnosing abnormal [Hb]. Therefore, we provide regression coefficients and reference-tables that are specific for world regions and altitude ranges to improve diagnosing abnormal [Hb].

Oxygen saturation thresholds for bronchiolitis at high altitudes: a cost-effectiveness analysis

ABSTRACT Background There is evidence suggesting that exaggerated reliance on pulse oximetry (SpO2) and the use of arbitrary/inadequate thresholds of SpO2 might drive unnecessary hospitalizations for viral bronchiolitis, especially among high-altitude residents. The aim of the present study was to compare the cost-effectiveness of two oxygen SpO2 thresholds for deciding whether infants with viral bronchiolitis living at high altitudes need hospital admission or can be discharged home. Methods A cost-effectiveness study was performed to compare the cost and clinical outcomes of two oxygen SpO2 thresholds, adjusted or not, to an altitude above the sea level of Bogota, Colombia (2640 m), for deciding whether infants with viral bronchiolitis need hospitalization or can be discharged home. The principal outcome was avoidance of hospital admission. Results Compared to the use of an SpO2 threshold of 90%, using an SpO2 threshold of 85% in infants with viral bronchiolitis was associated with lower overall costs (US$130.4 vs. US$194.0 average cost per patient) and a higher probability of hospitalization avoided (0.7500 vs. 0.5900), thus leading to dominance. Conclusions The use of an SpO2 threshold below 90% for deciding on hospitalization in infants with viral bronchiolitis living at high altitudes appears to be logical, secure, and cost-effective.

Excessive Erythrocytosis Is Not Associated With Altered Iron Homeostasis in Men From the World's Highest City.

Excessive Erythrocytosis Is Not Associated With Altered Iron Homeostasis in Men From the World's Highest City.

Decreased Vitamin D Levels and Altered Placental Vitamin D Gene Expression at High Altitude: Role of Genetic Ancestry.

High-altitude hypoxia challenges reproduction; particularly in non-native populations. Although high-altitude residence is associated with vitamin D deficiency, the homeostasis and metabolism of vitamin D in natives and migrants remain unknown. We report that high altitude (3600 m residence) negatively impacted vitamin D levels, with the high-altitude Andeans having the lowest 25-OH-D levels and the high-altitude Europeans having the lowest 1α,25-(OH)2-D levels. There was a significant interaction of genetic ancestry with altitude in the ratio of 1α,25-(OH)2-D to 25-OH-D; with the ratio being significantly lower in Europeans compared to Andeans living at high altitude. Placental gene expression accounted for as much as 50% of circulating vitamin D levels, with CYP2R1 (25-hydroxylase), CYP27B1 (1α-hydroxylase), CYP24A1 (24-hydroxylase), and LRP2 (megalin) as the major determinants of vitamin D levels. High-altitude residents had a greater correlation between circulating vitamin D levels and placental gene expression than low-altitude residents. Placental 7-dehydrocholesterol reductase and vitamin D receptor were upregulated at high altitude in both genetic-ancestry groups, while megalin and 24-hydroxylase were upregulated only in Europeans. Given that vitamin D deficiency and decreased 1α,25-(OH)2-D to 25-OH-D ratios are associated with pregnancy complications, our data support a role for high-altitude-induced vitamin D dysregulation impacting reproductive outcomes, particularly in migrants.

Quantify retinal structure in high-altitude residents with and without high altitude polycythemia

BackgroundTo assess retinal structural parameters in high-altitude (HA) residents with and without high altitude polycythemia (HAPC) and to elucidate the relationship between retinal structural parameters and hemoglobin (HGB).MethodsThis cross-sectional study included 55 HAPC patients and 52 healthy HA residents. Retinal structural parameters included retinal nerve fiber layer (RNFL) thickness, optic nerve head (ONH) parameters and retinal vessel diameter. RNFL thickness were acquired from spectral domain optical coherence tomography (SD-OCT) built-in software. ONH parameters including neuroretina rim height, cup area, disc area and vertical cup/disc ratio were obtained by OCT built-in software and ImageJ software. Retinal vessel measurements including central retinal artery equivalent (CRAE), central retinal vein equivalent (CRVE) and AVR (artery/vein ratio) were calculated by revised formulas for summarizing retinal vessel diameters. All parameters were compared between HAPC group versus healthy HA group. The associations between retinal parameters and HGB were assessed by Pearson correlation analyses.ResultsIn comparison of HAPC group versus healthy HA group, RNFL thickness was thicker in the nasal quadrant of the optic disc in HAPC group (74.82 ± 14.4 VS. 66.06 ± 13.71 μm, P = 0.002). Bigger disc area and bigger cup area were also observed in HAPC group (all P < 0.05). Meanwhile, the value of CRVE was higher in HAPC group which suggested that retinal veins dilated significantly in HAPC patients (P < 0.001), however, CRAE and AVR were comparable between groups. Pearson analyses revealed that HGB was positive correlated with CRVE in HAPC group (r = 0.469, P = 0.003).Conclusionslong-term HA exposure secondary HAPC could result in thickened RNFL, enlarged ONH and dilated retinal veins. Moreover, increased blood viscosity caused by HGB should be responsible for dilated veins, but not for thickened RNFL and enlarged ONH. This study deepens the understanding of the impact of HA environment on retina.

Regional peculiarities of specific immunity in inhabitants of different mountain heights of the Kyrgyz Republic

Kyrgyzstan’s challenging natural conditions and fragile mountain ecosystems can weaken the immune system of individuals residing permanently in high-altitude areas. Our study aimed to explore specific immune protection indicators in healthy populations from the Chui and Naryn regions at varying mountain altitudes. We assessed percentages of CD3+ (T-lymphocytes), CD20+ (B-lymphocytes), CD4+ (T-helper lymphocytes), CD8+ (cytotoxic T-lymphocytes), IRI (immunoregulatory index), CIC (circulating immune complexes), and quantified immunoglobulins of classes A, M, and G. Using immunofluorescent methods and monoclonal antibodies; we determined the percentages of CD3+, CD20+, CD4+, and CD8+. Radial immunodiffusion was used to quantify immunoglobulins of classes A, M, and G, while Falk’s method helped study CIC levels in blood sera. The participant count was based on statistical expert recommendations and G power analysis. The analysis revealed a decrease in the total number of T-lymphocytes (CD3+), primarily due to reduced T-helper and cytotoxic T-lymphocyte subpopulations. However, a significant increase in cytotoxic T-lymphocytes (CD8+) was observed among high-altitude residents. Mountain residents exhibited wide-ranging individual fluctuations for each immunoglobulin class. Our findings suggest varying degrees of immune mechanism disruptions, which maintain natural protection and internal environment constancy at different altitudes, resulting in a mixed type of cellular and humoral immunity suppression. These results emphasize the need for further research in the region and consideration of altitude when implementing disease prevention strategies related to the immune system for the local population.

COVID-19 Mortality Is Attenuated at High Tropical and Subtropical Altitude: An Observational Study of a Database Covering Five Latin American Countries

The COVID-19 pandemic, caused by the SARS-COV-2 virus, has had devastating consequences worldwide. Remarkably, the incidence, virus transmission capacity, and severity of COVID-19 have been reported to be significantly decreased in high-altitude human populations. The clinical significance of these findings is enormous, as they suggest that permanent inhabitants of high altitudes have developed adaptive protective changes against certain pathologies. However, these observations have been overshadowed by contradictory reports on the COVID-19 mortality rate at high altitude, ascribed to low population densities. These interpretations, however, fail to consider that the environmental conditions of high-altitude regions of the temperate and tropical geographical zones are radically different from each other. Contrary to common thought, the conditions of high-altitude areas of countries within the tropical zone are so benign that they have favored the growth and development of densely populated cities. In this work, we use data from a COVID-19 database covering five Latin American countries in the tropical and subtropical geographic zone that corresponded to the period between the start of the pandemic and the end of 2020, when no vaccine was yet available. Our results reveal that residing above 1,000 m in tropical countries was a protective factor against COVID-19 mortality. Interestingly, this protective effect was independent of population size. The findings presented here, and those from other similar studies, substantiate the need for more research to reveal the secrets of the physiology of permanent high-altitude residents. In conclusion, our findings clearly demonstrate that the high-altitude environment in tropical and subtropical geographic zones significantly contributes to the decreased mortality impact of the SARS-COV-2 virus in high-altitude-exposed populations.

Health Benefits of Residence at Moderate Altitude Do Not Reduce COVID-19 Mortality.

Moderate altitude (1000−2000 m above sea level) residence is emerging as a protective factor from the mortality of various causes, including of cardiovascular diseases. Conversely, mortality from certain respiratory diseases is higher at these altitudes than in lowlands. These divergent outcomes could indicate either beneficial or detrimental effects of altitude on the mortality of COVID-19 that primarily infects the respiratory tract but results in multi-organ damage. Previous epidemiological data indeed suggest divergent outcomes of moderate to high altitude residence in various countries. Confounding factors, such as variations in the access to clinical facilities or selection biases of investigated populations, may contribute to the equivocation of these observations. We interrogated a dataset of the complete population of an Alpine country in the center of Europe with relatively similar testing and clinical support conditions across altitude-levels of residence (up to around 2000 m) to assess altitude-dependent mortality from COVID-19 throughout 2020. While a reduced all-cause mortality was confirmed for people living higher than 1000 m, no differences in the mortality from COVID-19 between the lowest and the highest altitude regions were observed for the overall population and the population older than 60 years as well. Conversely, COVID-19 mortality seems to have been reduced in the very old (>85 years) women at moderate altitudes.

High altitude differentially modulates potassium channel-evoked vasodilatation in pregnant human myometrial arteries.

High-altitude (>2500m or 8200ft) residence reduces uterine artery blood flow during pregnancy, contributing to an increased incidence of preeclampsia and intrauterine growth restriction. However, not all pregnancies are affected by the chronic hypoxic conditions of high-altitude residence. K+ channels play important roles in the uterine vascular adaptation to pregnancy, promoting a reduction in myogenic tone and an increase in blood flow. We hypothesized that, in pregnancies with normal fetal growth at high altitude, K+ channel-dependent vasodilatation of myometrial arteries is increased compared to those from healthy pregnant women at a lower altitude (∼1700m). Using pharmacological modulation of two K+ channels, ATP-sensitive (KATP ) and large-conductance Ca2+ -activated (BKCa ) K+ channels, we assessed the vasodilatation of myometrial arteries from appropriate for gestational age (AGA) pregnancies in women living at high or low altitudes. In addition, we evaluated the localization of these channels in the myometrial arteries using immunofluorescence. Our results showed an endothelium-dependent increase in KATP -dependent vasodilatation in myometrial arteries from high versus low altitude, whereas vasodilatation induced by BKCa activation was reduced in these vessels. Additionally, KATP channel co-localization with endothelial markers was reduced in the high-altitude myometrial arteries, which suggested that the functional increase in KATP activity may be by mechanisms other than regulation of channel localization. These observations highlight an important contribution of K+ channels to the human uterine vascular adaptation to pregnancy at high altitude serving to maintain normal fetal growth under conditions of chronic hypoxia. KEY POINTS: High-altitude (>2500m or 8200ft) residence reduces uterine blood flow during pregnancy and fetal growth. Animal models of high altitude/chronic hypoxia suggest that these reductions are partially due to reduced vascular K+. channel responses, such as those elicited by large conductance Ca2+ -activated (BKCa ) and ATP-sensitive (KATP ) K+ channel activation. We found that women residing at high versus low altitude during pregnancy showed diminished myometrial artery vasodilatory responses to endothelium-independent BKCa channel activation but greater responses to endothelium-dependent KATP channel activation. Our observations indicate that KATP channels play an adaptive role in maintaining myometrial artery vasodilator sensitivity under chronic hypoxic conditions during pregnancy. Thus, KATP channels represent potential therapeutic targets for augmenting uteroplacental blood flow and, in turn, preserving fetal growth in cases of uteroplacental hypoperfusion.

Long COVID at Different Altitudes: A Countrywide Epidemiological Analysis.

Several reports from around the world have reported that some patients who have recovered from COVID-19 have experienced a range of persistent or new clinical symptoms after a SARS-CoV-2 infection. These symptoms can last from weeks to months, impacting everyday functioning to a significant number of patients. A cross-sectional analysis based on an online, self-reporting questionnaire was conducted in Ecuador from April to July 2022. Participants were invited by social media, radio, and TV to voluntarily participate in our study. A total of 2103 surveys were included in this study. We compared socio-demographic variables and long-term persisting symptoms at low (<2500 m) and high altitude (>2500 m). Overall, 1100 (52.3%) responders claimed to have Long-COVID symptoms after SARS-CoV-2 infection. Most of these were reported by women (64.0%); the most affected group was young adults between 21 to 40 years (68.5%), and most long-haulers were mestizos (91.6%). We found that high altitude residents were more likely to report persisting symptoms (71.7%) versus those living at lower altitudes (29.3%). The most common symptoms were fatigue or tiredness (8.4%), hair loss (5.1%) and difficulty concentrating (5.0%). The highest proportion of symptoms was observed in the group that received less than 2 doses. This is the first study describing post-COVID symptoms' persistence in low and high-altitude residents. Our findings demonstrate that women, especially those aging between 21-40, are more likely to describe Long-COVID. We also found that living at a high altitude was associated with higher reports of mood changes, tachycardia, decreased libido, insomnia, and palpitations compared to lowlanders. Finally, we found a greater risk to report Long-COVID symptoms among women, those with previous comorbidities and those who had a severer acute SARS-CoV-2 infection.

Anthropometric indices, body function, and physical fitness reference values for Tibetan ethnic children aged 6-17 residing at 3,650 meters above sea level.

ObjectivesIt is known that high altitude influences the growth metrics of high-altitude residents. Using a WHO-recommended standard, the research aimed to establish growth and development reference values for children of Tibetan ethnicity between the ages of 6 and 17 years old.MethodsThe measurements took place in Jomda County, Tibet with an average altitude of 3,650 m above sea level. A total of 3,955 observations (1,932 boys and 2,023 girls) were utilized to model the centile estimations. Included in the measurements are height, weight, body mass index, heart rate, blood pressure, forced lung capacity, sit and reach, and standing long jump. The measurements were modeled using the generalized additive models for location, scale, and shape (GAMLSS). Models were fitted with suitable distributions and locally smoothed using the P-spline for each GAMLSS hyper-parameter. Using the smallest Schwarz Bayesian criterion, the optimal model for each measurement was selected. After model adjustment, centile estimations were calculated for each model.ResultsCompared to the height reference values at the 50th percentile for multi-ethnic Chinese children residing at low altitudes, Tibetan ethnic children exhibit apparent stunted growth. In terms of forced vital capacity, it is remarkable that Tibetan ethnic children lag behind multi-ethnic Chinese children residing at low altitudes. Heart rate and blood pressure regulation are generally normal. Centile estimations are provided in this article and tabulated centiles (1p, 3p, 5p, 15p, 25p, 50p, 75p, 85p, 95p, 97p, 99p) in Chinese, Tibetic, and English are openly available in FigShare (doi: 10.6084/m9.figshare.20898196.v1).ConclusionThis study established the first GAMLSS based growth and development reference values for Tibetan ethnic children aged 6–17. These reference values have numerous clinical and scientific applications. We offer Chinese policymakers with practical initiatives to further enhance the health of Tibetan ethnic children.

Circulating Microparticles Are Differentially Increased in Lowlanders and Highlanders with High Altitude Induced Pulmonary Hypertension during the Cold Season.

The role of microparticles (MPs) and cold in high altitude pulmonary hypertension (HAPH) remains unexplored. We investigated the impact of long-term cold exposure on the pulmonary circulation in lowlanders and high-altitude natives and the role of MPs. Pulmonary hemodynamics were evaluated using Doppler echocardiography at the end of the colder and warmer seasons. We further examined the miRNA content of MPs isolated from the study participants and studied their effects on human pulmonary artery smooth muscle (hPASMCs) and endothelial cells (hPAECs). Long-term exposure to cold environment was associated with an enhanced pulmonary artery pressure in highlanders. Plasma levels of CD62E-positive and CD68-positive MPs increased in response to cold in lowlanders and HAPH highlanders. The miRNA-210 expression contained in MPs differentially changed in response to cold in lowlanders and highlanders. MPs isolated from lowlanders and highlanders increased proliferation and reduced apoptosis of hPASMCs. Further, MPs isolated from warm-exposed HAPH highlanders and cold-exposed highlanders exerted the most pronounced effects on VEGF expression in hPAECs. We demonstrated that prolonged exposure to cold is associated with elevated pulmonary artery pressures, which are most pronounced in high-altitude residents. Further, the numbers of circulating MPs are differentially increased in lowlanders and HAPH highlanders during the colder season.

Prevalence of Tuberculosis Among High Altitude Residents of Nepal

Introduction: Tuberculosis is a global health concern, and its prevalence can vary widely from one region to another. Factors such as altitude, climate, population density, and healthcare infrastructure can all influence the dynamics of Tuberculosis in a particular area. This study aimed to provide insights into whether altitude played a role in the occurrence of tuberculosis and its different forms in the specific region of Jumla the western rural district of Nepal. &#x0D; Methods: Jumla is a high-altitude mountainous region ranging from 915m- 4679 m with a population of 119,337 (2021) having 8 municipalities. Data were collected from all the municipalities over a period starting from July 15th2021-July 14th2022 and were compared with prior years in number and diagnosis with national data of Nepal. &#x0D; Results: A total of 84 cases were recorded of which 52.4% (n=44) were females. The group affected most was between the ages 16-30 years (34.5%) and 61-75yr (22.6%). The cases detected by the sputum Xpert MTB/RIF testing were 54.7%, with positive sputum Acid-fast bacilli being 27.4%. Most of the patients were diagnosed to have pulmonary bacteriologically confirmed (PBC) tuberculosis 52.4%, PCD (Pulmonary clinically diagnosed) 16.7%, Extra-pulmonary 28.6% with one case of each multi-drug resistant tuberculosis (MDR-TB), and Pre-XDR (Extensive drug resistant) TB. Among them, 12% of people had a history of TB undergone ATT (anti-tuberculosis drugs) in the past with 6% having a close contact history. &#x0D; Conclusions: Tuberculosis infection, disease, and mortality seem to be less common at high than low altitudes. As in Karnali Province, Humla with the second being Jumla has the lowest number of TB patients than other parts of Nepal, affecting younger people.

Assessing Severity of Chronic Obstructive lung disease (COPD) Using CAT score among high altitude residents of Nepal

Introduction: The goal of this study was to see if the Chronic Obstructive Pulmonary Disease (COPD) Assessment Test (CAT) score was beneficial in determining the severity of COPD patients. It produces a score that reflects the impact of the condition on their health status. GOLD guideline (2013) recommends CAT above other respiratory questionnaires since it is regarded to be a better assessment tool.&#x0D; Methods: Cross-sectional study conducted in Karnali Academy of Health Sciences, Jumla (Nepal) who presented with COPD exacerbation. A validated CAT questionnaire in the local language (Nepali) was employed and completed by the patient, and then the total CAT score was calculated and grouped into four impact levels. Data was evaluated using descriptive statistics (such as percentage and mean) and Pearson’s correlation tests to compare means.&#x0D; Results: Out of 55 patients, 52.7% were females; all 55 had firewood exposure with current smoking history more prevalent in the high-impact group 0.5%. At 3 months, the median number of COPD exacerbations was 2 (range: 0–90) with median CAT score 30 (range: 17–37). Patients were divided into severity groups based on their CAT scores. 47.3% were in the high impact group, whereas none were in the low impact group. The “very high impact” group had a considerably higher median number of exacerbations than the other high impact and medium groups (5 vs. 2 and 0) respectively with p&lt;0.001. In the “very high impact” group, significant use of inhalers in form of salbutamol or long-acting bronchodilators in combination with steroid was seen.&#x0D; Conclusions: CAT is an independent severity score that is higher in frequent exacerbates. The “very high impact” group had a considerably higher median number of exacerbations than the other groups (5 vs. 2 and 0) respectively with a significant p&lt;0.001 value. Thus, useful in monitoring patients health status and treatment.

Angelica archangelica and Ginkgo biloba Extracts Recover Functional Blood Hemoglobin Derivatives in Rabbits Exposed to High Altitude.

Shortage of oxygen is a common condition for residents of high-altitude (HA) areas. In mammals, hemoglobin (Hb) has four derivatives: oxyhemoglobin (Hb-O2), carboxyhemoglobin (Hb-CO), sulfhemoglobin (Hb-S), and methemoglobin (Met-Hb). In HA areas, aberrant physiological performance of blood hemoglobin is well-established. The study aimed to investigate the influence of 30 days of HA residence on rabbits' total Hb, Hb derivatives, Hb autooxidation rate, and antioxidant enzymes in comparison to low-altitude control rabbits. Further, the study aimed to investigate the effect of antioxidant-rich Angelica archangelica and/or Ginkgo biloba extracts on the same parameters in HA-resident rabbits. Rabbits subjected to 30 days of HA residence were compared to low-altitude control rabbits. HA-residence rabbits were then orally administered 0.11 g/kg b.wt. of Angelica archangelica and/or Ginkgo biloba extract for 14 days. Hb derivatives and Hb autooxidation rate were measured spectrophotometrically. Antioxidant enzymes were estimated using specialized kits. Compared to low-altitude rabbits, 30-day HA-residence rabbits showed a noticeable increase (p<0.05) in Hb-O2 and Hb-CO concentration. In addition, Met-Hb concentration, autooxidation rate of Hb molecules, and activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx) exhibited a remarkable increase in HA-residence rabbits (p<0.01), reflective of rapid ROS generation. In HA-residence rabbits, both individual and combined treatment with antioxidant-rich extracts for 14 days resulted in recovery to near-normal functional levels of Hb-O2 and Met-Hb, Hb autooxidation rate, and activities of SOD and GPx, while only combined treatment led to Hb-O2 recovery. The findings suggest that functional Hb levels may be recovered by oral administration of A. archangelica, G. biloba, or combined treatments. In conclusion, oxidative stress due to living in HA areas may be avoided by supplementation with natural antioxidants.

The Characteristics of Sleep Apnea in Tibetans and Han Long-Term High Altitude Residents.

PurposeObstructive sleep apnea (OSA) is common both at low and high altitude. Since adaptations to high altitude and respiratory control may differ among Tibetans and Hans, we compared characteristics of sleep-disordered breathing in the two ethnic groups at high altitude.Materials and MethodsThis was a prospective observational study including 86 Tibetan and Han long-term (>5 years) high altitude residents with chief complaints of snoring and/or witnessed apnea underwent clinical evaluation and polysomnography at 3200 meters in Shangri-La, China.ResultsIn 42 Tibetans, 38 men, median (quartiles) age was 50.0 (41.0; 56.0)y, total apnea/hypopnea index (AHI) 53.9 (32.0; 77.5)/h, obstructive AHI 51.0 (28.0; 72.2)/h and central AHI 1.5 (0.2; 3.1)/h. In 44 Hans, 32 men, median (quartiles) age was 47.0 (43.5; 51.0)y, total AHI 22.2 (12.8; 39.2)/h, obstructive AHI 17.7 (12.0; 33.0)/h and central AHI 2.4 (0.5; 3.4)/h (p < 0.001 total and obstructive AHI vs Tibetans). In Tibetans, mean nocturnal oxygen saturation was lower [median 85.0 (83.0; 88.0)% vs 88.5 (87.0; 90.0)%] and obstructive apnea and hypopnea duration was longer [22.0 (19.6; 24.8) sec vs 18.3 (16.7; 20.6) sec] than in Hans (all p < 0.001). In regression analysis, Tibetan ethnicity, neck circumference and high-altitude living duration were the predictors of total AHI. We also found that with every 10/h increase in total AHI, there were an approximately 0.9 beat/min and 0.8 beat/min increase in mean heart rate during rapid eye movement (REM) and non-REM sleep and 1.9 mmHg and 2.0 mmHg increase in evening and morning systolic blood pressure.ConclusionOur data suggest that Tibetans presented more severe obstructive sleep apnea, hypoxemia and longer apnea duration compared to Hans at 3200 meters, which was correlated with higher heart rate and blood pressure suggesting a greater cardiovascular risk.

Effects of Moderate Altitude Training Combined with Moderate or High-altitude Residence.

We aimed to identify potential physiological and performance differences of trained cross-country skiers (V˙o2max=60±4 ml ∙ kg-1 ∙ min-1) following two, 3-week long altitude modalities: 1) training at moderate altitudes (600-1700 m) and living at 1500 m (LMTM;N=8); and 2) training at moderate altitudes (600-1700 m) and living at 1500 m with additional nocturnal normobaric hypoxic exposures (FiO2 =0.17;LHTM; N=8). All participants conducted the same training throughout the altitude training phase and underwent maximal roller ski trials and submaximal cyclo-ergometery before, during and one week after the training camps. No exercise performance or hematological differences were observed between the two modalities. The average roller ski velocities were increased one week after the training camps following both LMTM (p=0.03) and LHTM (p=0.04) with no difference between the two (p=0.68). During the submaximal test, LMTM increased the Tissue Oxygenation Index (11.5±6.5 to 1.0±8.5%; p=0.04), decreased the total hemoglobin concentration (15.1±6.5 to 1.7±12.9 a.u.;p=0.02), and increased blood pH (7.36±0.03 to 7.39±0.03;p=0.03). On the other hand, LHTM augmented minute ventilation (76±14 to 88±10 l·min-1;p=0.04) and systemic blood oxygen saturation by 2±1%; (p=0.02) with no such differences observed following the LMTM. Collectively, despite minor physiological differences observed between the two tested altitude training modalities both induced comparable exercise performance modulation.

Effects of long-term high-altitude exposure on retinal and choroidal microcirculation

To quantify the effect of long-term high-altitude (HA) exposure on retinal and choroidal microcirculation and to relate these changes to high-altitude polycythemia (HAPC), as a proxy for etiopathogenesis of high-altitude related retinopathy (HAR). Fifty-one HAPC patients, 50 healthy HA residents, and 43 low altitude (LA) residents were recruited in this study. Optical coherence tomography angiography (OCTA) and enhanced depth imaging (EDI)-OCT images were analyzed. Retinal microvascular metrics included vessel density (VD), skeleton density (SD), fractal dimension (FD), and foveal avascular zone (FAZ). Choroidal microvascular metrics included subfoveal choroidal thickness (SFCT) and choroidal vascularity index (CVI). All metrics were calculated by ImageJ software and compared among HAPC group, healthy HA group, and LA group. In HAPC group, VD (30.62 ± 3.67%), SD (13.25 ± 1.64%), FD (1.79 ± 0.04), and the CVI (63.01 ± 1.42%) were significant lower and SFCT (403.25 ± 94.3μm) was significant thicker than healthy HA group (all P < 0.001). FAZ area was comparable between two groups (0.42 ± 0.1 vs. 0.4 ± 0.11 mm2, P = 0.411). However, these metrics were not different between healthy HA group and LA group (all P > 0.05) except for FD was lower in HA group (P < 0.001). Pearson's correlation analyses revealed HGB was negatively related with VD (r = - 0.562, P < 0.001) and positively related with SFCT (r = 0.505, P < 0.001) in healthy HA group; however, no associations between HGB and vascular metrics in HAPC group were detected (all P > 0.05). Long-term exposure to HA environment induces retinal and choroidal microcirculation disturbance in HAPC patients. However, these changes were not evident in healthy HA residents because of adaptation.