Acute Mountain Sickness Research Articles

17 The Rumen Microbiome: Realizing the Potential for Mediating Host Performance

Abstract The rumen microbiome has a critical role in multiple facets of ruminant livestock production. It is well known that the rumen microbiome is integral to animal performance through impacts on feed efficiency, greenhouse gas production, volatile fatty acid production, and numerous aspects of animal health. Therefore, understanding factors that influence the rumen microbiome at various stages of the production cycle and the interactions with other microbial niches and physiological processes is a critical area of research to aid in the goal of improving livestock performance. Our research objectives have focused on 3 primary general areas including 1) to characterize and understand the potential pathways of early gut colonization from conception throughout gestation, 2) implications of varying gestational perturbations on rumen microbiome development and calf performance post-weaning, and 3) understand the connections between the rumen microbiome and the microbiomes of the reproductive tract, blood, and respiratory tract. We hypothesize that strategies to program the rumen microbiome early in life may have lasting impacts on host performance specific to feed efficiency, reproductive fitness, and have implications on high altitude disease. These effects may not be a direct relationship between the rumen microbiome and host response, but rather through a total system level response that has the rumen microbiome as a key player in that cascade. The rumen microbiome has the potential to impact numerous aspects of host performance, as such, it is imperative that research continues to elucidate its role in host physiology and the development of intervention mechanisms to initiate specific responses in the rumen microbiome to improve downstream host response.

A Randomized Phase 2 Study to Evaluate Efficacy and Safety of AR36 for Prevention of Acute Mountain Sickness

AR36 is a pharmaceutical-grade plant extract used to support cardiovascular health in traditional Chinese medicine. Studies suggest that AR36 may prevent acute mountain sickness (AMS) during gradual ascent to high altitude. This randomized, placebo-controlled Phase 2 trial aimed to evaluate dosing regimens and assess efficacy and safety of AR36 for AMS prevention during rapid ascent. Participants received placebo, low-dose AR36 (225 mg twice daily for 14 d prior and 5 d at altitude), or high-dose AR36 (12 d placebo, 300 mg twice daily for 2 d prior and 5 d at altitude). The primary efficacy outcome was 1993 Lake Louise Scoring System (LLSS) score on the morning after ascent. Safety was assessed through the proportion of treatment-emergent adverse events (TEAEs). One hundred thirty-two participants were randomized. Mean±SD age was 31.4±8.6 (range, 19-54) y. Baseline characteristics did not differ across groups. Lake Louise Scoring System scores on Day 16 in the placebo, low-dose, and high-dose groups were 4.03 (2.88), 4.42 (3.17), and 3.5 (2.31), respectively (placebo versus low-dose, P=0.462; placebo versus high-dose, P=0.574; n=110). The incidence of AMS on Day 16 was 66.7% in the placebo, 61.1% in the low-dose, and 55.3% in the high-dose group (P=0.66). The proportion of TEAEs in the placebo, low-dose, and high-dose groups was 38.4% (81), 28.4% (60), and 33.2% (70), respectively (P=0.205; n=127). There was no statistical difference between groups in LLSS, incidence of AMS, or TEAEs. AR36 did not improve LLSS or AMS incidence using the current regimens. AR36 was well tolerated.

Anxiety as a Risk Factor for Acute Mountain Sickness Among Young Chinese Men After Exposure at 3800 M: A cross‒sectional Study.

We aimed to explore whether anxiety is a risk factor for acute mountain sickness [AMS] in a young Chinese male population. A total of 143 young Chinese men with a median age of 23 years (IQR, 21-25) were employed in the present study, and they were divided into the AMS+ and AMS- groups according to the Lake Louise AMS score [AMS-S] after exposure at 3800 m for two days. Participants' pulse oximeter saturation [SpO2] and heart rate [HR] were measured. AMS was evaluated using the AMS-S. The anxiety and sleep quality of the subjects were assessed using the Zung Self-Rating Anxiety Scale [SAS] and the Athens Insomnia Scale [AIS], respectively. Outcomes were analysed using Spearman's partial correlation and logistic regression analysis. After two days of exposure at 3800 m, the overall prevalence of AMS was 54% in the whole group. The HR was significantly higher in the AMS+ group than in the AMS- group, as well as the SAS score and AIS score. A converse pattern was observed for SpO2. A significant difference was observed for the change in SAS and AIS score between the AMS+ and AMS- groups. Correlation analysis showed that AMS-S was positively correlated with SAS score, AIS score, HR, ΔSAS score, ΔAIS score, and ΔHR but negatively correlated with SpO2. AIS score was positively correlated with SAS score. After logistic regression analysis was adjusted for HR, SpO2, ΔAIS and ΔHR, SAS score (OR=1.446, 95% CI 1.200-1.744, p<0.001), AIS score (OR=1.216, 95% CI 1.033-1.432) and ΔSAS score (OR=1.158, 95% CI 1.012-1.327) were identified as independent risk factors for AMS. The present study suggests that anxiety is a risk factor for AMS among young Chinese men, and poor sleep quality may partially mediate the association.

Exercise performance reduction and preventive measures in highland sports.

The plateau is a special environment with low pressure, low oxygen, low temperature, and high ultraviolet radiation. The exercise performance of people on the plateau is generally reduced, which seriously affects the life and health of people living in the plateau and entering the plateau. In recent years, the prevention and treatment of injury caused by high altitude hypoxia has attracted wide attention. It has shown that the higher the altitude with the longer the duration of exercise, the faster the stationing, the greater the impact on people's sports performance. Rapid entry into the plateau and long-term stay in the plateau have an impact on people's explosive power, endurance and fine operation. Advances in medical technology enable various prevention methods to be used to acclimate to high altitude environments. However, in vitro intervention methods are costly, easy to rebound and possess limited effects. Therefore, drug prevention and treatment is obviously a more economical choice. Chemical drugs increase the efficiency of high altitude exercise by improving the ischemic and hypoxic symptoms of the heart and brain, increasing lung ventilation and arterial oxygenation capacity, and accelerating the elimination of adverse product accumulation after exercise. Single Chinese medicine, Chinese patent medicine, and compound preparations can improve exercise performance by promoting body metabolism, improving muscle endurance, enhancing immunity, and other mechanisms. Traditional Chinese medicine has unique advantage and application prospect in improving plateau sports performance damage.

Medication rule of traditional Chinese medicine in the treatment of plateau hypoxia based on data mining.

The development of traditional Chinese medicine (TCM) in the plateau area is relatively backward. There is a lack of system to analyze the effects of the special environment of plateau low pressure and hypoxia on human meridians qi and blood, as well as the etiology and pathogenesis of plateau hypoxic diseases. To analyze the composition rules of anti-hypoxia TCM formulation with data mining methods. The experimental literatures related to high altitude hypoxia were searched in China National Knowledge Infrastructure (CNKI), Wanfang Med Online, VIP, China Biology Medicine disc and other databases, a standardized prescription database was established after screening and standardization of prescription data in the literature. The composition rules of these prescription including drug frequency, drug attributes, drug efficacy, drug combination, and core prescription were analyzed and displayed with visual charts. A total of 135 TCM prescriptions were included, and 229 flavored drugs were included. Among these prescriptions, the TCM with high frequency of use were Astragalus, Danshen, Ginseng, and Angelica, etc. Four natures of the TCM were mostly warm and calm. Five flavours of the TCM were mostly sweet, bitter, and pungent. And channel tropism of the TCM mostly entered the heart, lung, and liver meridians. The frequency combination of TCM was Astragalus-Danshen and Astragalus-Angelica. The core medicines of these prescriptions were Astragalus, Danshen, Angelica, Rhodiola, Goji, and Ginseng. TCM could alleviate symptoms such as chest tightness, chest pain, coughing and wheezing, coughing, vomiting, fatigue, and loss of appetite caused by hypoxia at high altitude. Through data mining, it is concluded that the prevention or treatment of plateau hypoxic diseases mostly utilized products can nourish blood, replenish qi and dispel stasis, and help yang and dispel qi, most of them are compatible with qi tonic drugs and blood circulation and stasis dissolving drugs, and pay attention to the combination of virtual and real, yin and yang.

Acétazolamide et effusion uvéale : à propos de deux cas

We report two cases of uveal effusion following oral acetazolamide administration: one case after a standard cataract surgery and a second following a preventive treatment for altitude sickness. The outcome in both cases was favorable. This rare complication requires appropriate management, including ruling out other pathologies. The pathophysiological mechanism is not fully understood.

Women's Health at High Altitude: An Introduction to a 7-Part Series by the International Climbing and Mountaineering Federation Medical Commission.

Horakova, Lenka, Peter Paal, Jacqueline Pichler Hefti, Marija Andjelkovic, Beth A. Beidleman, Mia Derstine, David Hillebrandt, Dominique Jean, Kastė Mateikaitė-Pipirienė, Alison J. Rosier, Susi Kriemler, and Linda E. Keyes. Women's health at high altitude: An introduction to a 7-part series by the International Climbing and Mountaineering Federation Medical Commission. High Alt Med Biol. 24:243-246, 2023. Background: Women have been traveling to high altitude since the inception of modern mountaineering. Although there are distinct female-specific features such as menstruation and menopause relevant to adaptation to and performance at high altitude, very little data exist on women's high-altitude health. To summarize what is known to date, the Medical Commission of the International Climbing and Mountaineering Federation (UIAA) has created a series of articles on women's health, high altitude illness, and performance at high altitude. Methods: Assembling an international author team, two types of manuscripts were developed: (1) reviews on female-specific topics such as pregnancy; (2) reviews on sex differences in high-altitude related illnesses, nutrition, cold injuries, and mortality. Results: The literature search yielded 7,165 articles, with 482 studies meeting the inclusion criteria for full-text review. The authors of individual chapters reviewed these articles and performed additional hand searches. Conclusions: Some important questions on women sojourning and exercising at high altitude have been studied, but many are still awaiting a qualified and evidence-based response. Our seven reviews, to be published in future issues of this journal, summarize what is known about lowland women sojourning at high altitude, provide recommendations, and highlight knowledge gaps in high altitude women's medicine.

Oxygen enrichment protects against intestinal damage and gut microbiota disturbance in rats exposed to acute high-altitude hypoxia.

Acute high-altitude hypoxia can lead to intestinal damage and changes in gut microbiota. Sustained and reliable oxygen enrichment can resist hypoxic damage at high altitude to a certain extent. However, it remains unclear whether oxygen enrichment can protect against gut damage and changes in intestinal flora caused by acute altitude hypoxia. For this study, eighteen male Sprague-Dawley rats were divided into three groups, control (NN), hypobaric hypoxic (HH), and oxygen-enriched (HO). The NN group was raised under normobaric normoxia, whereas the HH group was placed in a hypobaric hypoxic chamber simulating 7,000 m for 3 days. The HO group was exposed to oxygen-enriched air in the same hypobaric hypoxic chamber as the HH group for 12 h daily. Our findings indicate that an acute HH environment caused a fracture of the crypt structure, loss of epithelial cells, and reduction in goblet cells. Additionally, the structure and diversity of bacteria decreased in richness and evenness. The species composition at Phylum and Genus level was characterized by a higher ratio of Firmicutes and Bacteroides and an increased abundance of Lactobacillus with the abundance of Prevotellaceae_NK3B31_group decreased in the HH group. Interestingly, after oxygen enrichment intervention, the intestinal injury was significantly restrained. This was confirmed by an increase in the crypt depth, intact epithelial cell morphology, increased relative density of goblet cells, and higher evenness and richness of the gut microbiota, Bacteroidetes and Prevotellaceae as the main microbiota in the HO group. Finally, functional analysis showed significant differences between the different groups with respect to different metabolic pathways, including Amino acid metabolism, energy metabolism, and metabolism. In conclusion, this study verifies, for the first time, the positive effects of oxygen enrichment on gut structure and microbiota in animals experiencing acute hypobaric hypoxia.

WITHDRAWN: Wilderness Medical Society Clinical Practice Guidelines for the Prevention, Diagnosis, and Treatment of Acute Altitude Illness: 2024 Update

To provide guidance to clinicians about best practices, the Wilderness Medical Society (WMS) convened an expert panel to develop evidence-based guidelines for prevention, diagnosis, and treatment of acute mountain sickness, high altitude cerebral edema, and high altitude pulmonary edema. Recommendations are graded based on the quality of supporting evidence and the balance between the benefits and risks/burdens according to criteria put forth by the American College of Chest Physicians. The guidelines also provide suggested approaches for managing each form of acute altitude illness that incorporate these recommendations as well as recommendations on how to approach high altitude travel following COVID-19 infection. This is an updated version of the original WMS Consensus Guidelines for the Prevention and Treatment of Acute Altitude Illness published in Wilderness & Environmental Medicine in 2010 and the subsequently updated WMS Practice Guidelines for the Prevention and Treatment of Acute Altitude Illness published in 2014 and 2019.

The Effect of High-Altitude Hypoxia on Neuropsychiatric Functions.

Liu, Bo, Minlan Yuan, Mei Yang, Hongru Zhu, and Wei Zhang. The effect of high-altitude hypoxia on neuropsychiatric functions. High Alt Med Biol. 25:26-41, 2024. Background: In recent years, there has been a growing popularity in engaging in activities at high altitudes, such as hiking and work. However, these high-altitude environments pose risks of hypoxia, which can lead to various acute or chronic cerebral diseases. These conditions include common neurological diseases such as acute mountain sickness (AMS), high-altitude cerebral edema, and altitude-related cerebrovascular diseases, as well as psychiatric disorders such as anxiety, depression, and psychosis. However, reviews of altitude-related neuropsychiatric conditions and their potential mechanisms are rare. Methods: We conducted searches on PubMed and Google Scholar, exploring existing literature encompassing preclinical and clinical studies. Our aim was to summarize the prevalent neuropsychiatric diseases induced by altitude hypoxia, the potential pathophysiological mechanisms, as well as the available pharmacological and nonpharmacological strategies for prevention and intervention. Results: The development of altitude-related cerebral diseases may arise from various pathogenic processes, including neurovascular alterations associated with hypoxia, cytotoxic responses, activation of reactive oxygen species, and dysregulation of the expression of hypoxia inducible factor-1 and nuclear factor erythroid 2-related factor 2. Furthermore, the interplay between hypoxia-induced neurological and psychiatric changes is believed to play a role in the progression of brain damage. Conclusions: While there is some evidence pointing to pathophysiological changes in hypoxia-induced brain damage, the precise mechanisms responsible for neuropsychiatric alterations remain elusive. Currently, the range of prevention and intervention strategies available is primarily focused on addressing AMS, with a preference for prevention rather than treatment.

Carbonic anhydrase inhibition by antiviral drugs in vitro and in silico.

Enzyme inhibition is a commonly utilized method for controlling enzymatic activity in various physiologically relevant biological systems. Herein, the selected five active antiviral drugs, abacavir, emtricitabine, lamivudine, ribavirin, and ritonavir, were assayed as inhibitors of two human isoforms of the metalloenzyme carbonic anhydrase (hCA, EC 4.2.1.1) involved in various physiological/pathological conditions. For this aim, in vitro and in silico studies were performed to gain insights into the plausible binding interactions and affinities for the antiviral drugs within hCA I and II isoforms' active sites. The hCA I, an isoform involved in some pathological conditions such as retinal or cerebral edema, was moderately inhibited by these five drugs at micromolar concentrations with KI s spanning from 0.49 ± 0.05 to 3.51 ± 0.37 μM compared with the reference drug acetazolamide (AAZ, KI of 0.19 ± 0.01 μM). Moreover, hCA II, a promising target for edema, glaucoma, epilepsy, and altitude sickness, was a reasonably inhibited isoform by these agents, with KI s in the range of 0.64 ± 0.08-5.80 ± 0.64 μM compared with AAZ (KI of 0.17 ± 0.01 μM). Both in vitro and in silico results demonstrated significant interactions between these five drugs and hCAs and that they can support therapeutic targets against the above-mentioned pathological conditions. Additionally, the results obtained will help optimize the clinical dosage regimens of these drugs and avoid drug-drug interactions unexpectedly when used in combination with other agents.

The role of hypoxia related hormones responses in acute mountain sickness susceptibility individuals unaccustomed to high altitude.

Acute mountain sickness (AMS) is caused by rapid ascent to altitude (>2500 m) and remains a poorly understood pathophysiological condition. Accordingly, we investigated the relationship between acute exposure to high altitude and hypoxia related biochemical proteins. 21 healthy subjects (Female (8) and male (13), Age: 36.7±8.5, BMI: 23.2±3.1) volunteers participated in this project and fasting blood samples were taken before (sea level) and after 1 and 24-h exposure to high altitude (3,550 m). Blood oxygen saturation (SpO2), AMS status (Lake Louise Score) and serum HIF-1, Endothelin-1, VEGF and Orexin-A were measured (via ELISA) at 1, 6 and 24 h after exposure to high altitude. Pre-ascent measurement of hypoxia related proteins (Orexin-A, HIF-1, VEGF and Endothelin-1) where all significantly (<0.05) higher in the AMS-resistant individuals (No-AMS) when compared to AMS susceptible individuals (AMS+). Upon ascent to high altitude, 11 out of 21 volunteers had AMS (10.1±0.6 in AMS+ vs. 0.9±0.6 in No-AMS, P<0.05) and presented with lower resting SpO2 levels (77.7±0.4 vs. 83.5±0.3 respectively, p<0.05). Orexin-A, HIF-1, VEGF and Endothelin-1, significantly increased 24 hrs after exposure to high altitude in both AMS+ and No-AMS. The response of Orexin-A was similar between two groups, also, HIF-1 elevation 24 hrs after exposure to altitude was more in AMS+ (13% vs. 19%), but the increase of VEGF and Endothelin-1, 1 and 24 hrs after exposure to altitude in No-AMS was double that of AMS+. Hypoxia related proteins include Orexin-A, HIF-1, VEGF and Endothelin-1 may play a pathophysiological role in those who are susceptible to AMS.

Brain-aging related protein expression and imaging characteristics of mice exposed to chronic hypoxia at high altitude.

To determine changes in protein expression related to brain aging and imaging features in mice after chronic hypoxia exposure at high altitude. A total of 24 healthy 4-week-old mice were randomly divided into high altitude hypoxia (HH) and plain control (PC) groups (n = 8 per group). HH mice were transported from Xi'an (450 m above sea level) to Maduo (4,300 m above sea level) while PC mice were raised in Xi'an. After 6 months, 7.0T magnetic resonance imaging (MRI) was performed. All mice completed T2-weighted imaging (T2WI), diffusion tensor imaging (DTI), resting-state functional MRI (rs-fMRI), arterial spin labeling (ASL), and magnetic resonance angiography (MRA) examinations. Next, brain slices were prepared and Nissl staining was used to observe morphological changes in neurons. Ultrastructural changes in neurons were observed by transmission electron microscopy. Expression changes of Caspase-3, klotho, P16, P21, and P53 at the gene and protein levels were detected by real-time PCR (RT-PCR) and Western blot. The number of neuronal Nissl bodies in the hippocampus and frontal cortex was significantly decreased in the HH group compared to the PC group. Some hippocampal and frontal cortical neurons were apoptotic, the nuclei were wrinkled, chromatin was aggregated, and most mitochondria were mildly swollen (crista lysis, fracture). Compared with the PC group, the HH group showed elevated expression of caspase-3 mRNA, P16 mRNA, P21 mRNA, and P53 mRNA in the hippocampus and frontal cortex. Expression of Klotho mRNA in the frontal cortex was also significantly decreased. Western blot results showed that caspase-3 protein expression in the hippocampus and frontal cortex of the HH group was increased compared with the PC group. Moreover, there was decreased Klotho protein expression and significantly increased P-P53 protein expression. Compared with the PC group, expression of P16 protein in the frontal cortex of the HH group was increased and the gray matter (GM) volume in the left visceral area, left caudate nucleus, and left piriform cortex was decreased. Furthermore, the amplitude of low frequency fluctuation was decreased in the left posterior nongranular insular lobe, right small cell reticular nucleus, left flocculus, left accessory flocculus, and left primary auditory area, but increased in the GM layer of the left superior colliculus. Regional homogeneity was decreased in the left and right olfactory regions, but increased in the left bed nucleus. After exposure to high altitude, functional connectivity (FC) between the bilateral caudate nucleus and thalamus, corpus callosum, cingulate gyrus, anterior limbic cortex, globus pallidus, and hippocampus was weakened. FC between the right caudate nucleus and hypothalamus and entorhinal cortex was also weakened. The fractional anisotropy value of the left hippocampus was decreased in the HH group. Compared with the PC group, the HH group showed significantly increased inner diameters of the bilateral common carotid artery and left internal carotid artery. The cerebral blood flow values of the bilateral cortex and bilateral hippocampus in the HH group did not change significantly. Taken together, our findings show that chronic hypoxia exposure at high altitude may promote neuronal apoptosis and abnormal expression of related proteins, changing the structure and function of brain. These changes may contribute to brain aging.

Comprehensive Investigation of the Influence of High-Altitude Hypoxia on Clopidogrel Metabolism and Gut Microbiota.

The amount of metabolites converted into active metabolites is correspondingly reduced since only more than 50% of clopidogrel is absorbed. Exploring the effect of gut microbiota altered by altitude hypoxia on the pre-absorption metabolism of clopidogrel. In vitro and in vivo experiments were conducted to analyze the metabolism of clopidogrel through LCMS/ MS, while 16S rRNA analysis was used to investigate the changes in the gut microbiota of high-altitude animals. We demonstrated that the intestinal flora is involved in the metabolism of clopidogrel through in vivo and in vitro experiments. In addition, the plateau environment caused changes in the number and composition of intestinal microbes. Intriguingly, alterations in the microbial population could lead to an increase in the pre-absorption metabolism of clopidogrel after rapid entry into the plateau, the amount of absorbed blood is thus reduced, which may affect the bioavailability and therapeutic effect of clopidogrel. Our results not only as a first clinical reference for dose adjustment of clopidogrel in high-altitude environments but also would be helpful to provide a statement on the broader significance within the field of pharmacokinetics or personalized medicine.

Potential plasma biomarkers at low altitude for prediction of acute mountain sickness.

Ascending to high altitude can induce a range of physiological and molecular alterations, rendering a proportion of lowlanders unacclimatized. The prediction of acute mountain sickness (AMS) prior to ascent to high altitude remains elusive. A total of 40 participants were enrolled for our study in the discovery cohort, and plasma samples were collected from all individuals. The subjects were divided into severe AMS-susceptible (sAMS) group, moderate AMS-susceptible (mAMS) group and non-AMS group based on the Lake Louise Score (LLS) at both 5000m and 3700m. Proteomic analysis was conducted on a cohort of 40 individuals to elucidate differentially expressed proteins (DEPs) and associated pathways between AMS-susceptible group and AMS-resistant group at low altitude (1400m) and middle high-altitude (3700m). Subsequently, a validation cohort consisting of 118 individuals was enrolled. The plasma concentration of selected DEPs were quantified using ELISA. Comparative analyses of DEPs among different groups in validation cohort were performed, followed by Receiver Operating Characteristic (ROC) analysis to evaluate the predictive efficiency of DEPs for the occurrence of AMS. The occurrence of the AMS symptoms and LLS differed significantly among the three groups in the discovery cohort (p<0.05), as well as in the validation cohort. Comparison of plasma protein profiles using GO analysis revealed that DEPs were primarily enriched in granulocyte activation, neutrophil mediated immunity, and humoral immune response. The comparison of potential biomarkers between the sAMS group and non-AMS group at low altitude revealed statistically higher levels of AAT, SAP and LTF in sAMS group (p=0.01), with a combined area under the curve(AUC) of 0.965. Compared to the mAMS group at low altitude, both SAP and LTF were found to be significantly elevated in the sAMS group, with a combined AUC of 0.887. HSP90-α and SAP exhibited statistically higher levels in the mAMS group compared to the non-AMS group at low altitude, with a combined AUC of 0.874. Inflammatory and immune related biological processes were significantly different between AMS-susceptible and AMS-resistant groups at low altitude and middle high-altitude. SAP, AAT, LTF and HSP90-α were considered as potential biomarkers at low altitude for the prediction of AMS.

Load carriage physiology in normoxia and hypoxia

PurposeTo determine the effects of load carriage in normoxia and normobaric hypoxia on ventilatory responses, hemodynamics, tissue oxygenation, and metabolism.MethodsHealthy males (n = 12) completed 3 randomly ordered baseline graded exercise tests in the following conditions: (1) unloaded normoxic (U: FIO2 = 20.93%), (2) loaded (~ 30 kg) normoxic (LN), and (3) loaded hypoxic simulating ~ 3650 m (LH: FIO2 = ~ 13%). Thereafter, experimental exercise trials were completed in quasi-randomized order (i.e., U completed first) consisting of 3 × 10 min of walking (separated by 5 min seated rest) with stages matched with the U condition (in ascending order) for relative intensity, absolute oxygen consumption ([VO2]; 1.7 L min−1), and walking speed (1.45 ± 0.15 m s−1).ResultsLoad carriage increased perceived exertion and reduced VO2max (LN: − 7%; LH: − 32%; p < 0.05). At matched VO2, stroke volume and tidal volume were reduced and maintained with LN and LH vs. U, respectively (p < 0.05). Increases in cardiac output and minute ventilation at matched VO2 (with LH) and speed (with LN and LH), were primarily accomplished via increases in heart rate and breathing frequency (p < 0.05). Cerebral oxygenated hemoglobin (O2HHb) was increased at all intensities with LN, but deoxygenated hemoglobin and total hemoglobin were increased with LH (p < 0.05). Muscle oxygen kinetics and substrate utilization were similar between LN and U, but LH increased CHO dependence and reduced muscle O2HHb at matched speed (p < 0.05).ConclusionLoad carriage reduces cardiorespiratory efficiency and increases physiological strain, particularly in hypoxic environments. Potential load carriage-induced alterations in cerebral blood flow may increase the risk for altitude illnesses and requires further study.

Angiotensin-Converting Enzyme (ACE) gene polymorphism and arterial blood pressure among the Tawang Monpa of Eastern Himalayan Mountains: Is there a signature of natural selection?

The present paper aims to characterize the Angiotensin-converting enzyme (ACE) genotype, with particular emphasis on its association with arterial oxygen saturation, arterial blood pressure, hemoglobin [Hb] concentration, and ventilatory measures among the Tawang Monpa, a high-altitude native population of the Eastern Himalaya, India. A cross-sectional sample of 168Monpa participants from Tawang town, Arunachal Pradesh, India, was selected who live at an altitude of ∼3,200 meters (m) above sea level. For each participant, height, weight, and skinfold thickness were measured, based on which body mass index (BMI, kg/m2) and percentage of body fat (%BF) were calculated. Physiological measures, such as the transcutaneous arterial oxygen saturation (SaO2), hemoglobin [Hb] concentration, forced vital capacity (FVC), forced expiratory volume in 1-second (FEV1), and systemic arterial blood pressure were measured. First, the peripheral venous blood samples (four ml) were drawn, and then white blood cells were separated for the ACE genotyping of each participant. Unlike high-altitude natives from Peru and Ladakh, who exhibit high frequencies of II homozygotes, the Tawang Monpa shows a significantly high frequency of ID heterozygotes (p<0.0001). In addition, no significant association was identified between ACE gene polymorphism and arterial blood pressure, oxygen saturation at rest, vital capacity, or [Hb] concentration. The results suggest that the association of the ACE gene with resting SaO2 is inconsistent across native populations living under hypobaric hypoxia. Further, ACE I/D gene polymorphism may not be under natural selection in specific native populations, including Tawang Monpa, for their adaptation to high-altitude hypoxia.

Prevalence and knowledge about acute mountain sickness in the Western Alps.

To assess the prevalence of acute mountain sickness (AMS) in 1370 mountaineers at four different altitudes in the Western Alps. We also examined the influence of potential risk factors and the knowledge about AMS on its prevalence. In this observational cross-sectional study AMS was assessed on the day of ascent by the Lake Louise score (LLS, cut-off ≥3, version 2018) and the AMS-Cerebral (AMS-C) score of the environmental symptom questionnaire (cut-off ≥0,70). The latter was also obtained in the next morning. Knowledge regarding AMS and high-altitude cerebral edema (HACE) and the potential risk factors for AMS were evaluated by questionnaires. On the day of ascent, the prevalence of AMS assessed by the LLS and AMS-C score was 5.8 and 3.9% at 2850 m, 2.1 and 3.1% at 3050 m, 14.8 and 10.1% at 3650 m, and 21.9 and 15% at 4559 m, respectively. The AMS prevalence increased overnight from 10.1 to 14.5% and from 15 to 25.2% at 3650 m and 4559 m, respectively, and was unchanged at 2850 m and 3050 m. A history of AMS, higher altitude, lower degree of pre-acclimatization, and younger age were identified as risk factors for developing AMS. Slow ascent was weakly associated with AMS prevalence, and sex and knowledge about AMS and HACE were indistinct. AMS is common at altitudes ≥ 3650 m and better knowledge about AMS and HACE was not associated with less AMS in mountaineers with on average little knowledge.

Effects of Hypoxemia by Acute High-Altitude Exposure on Human Intestinal Flora and Metabolism.

This study examined the effects of hypoxemia caused by acute high-altitude hypoxia (AHAH) exposure on the human intestinal flora and its metabolites. The changes in the intestinal flora, metabolism, and erythropoietin content in the AHAH population under altitude hypoxia conditions were comprehensively analyzed using 16S rRNA sequencing, metabonomics, and erythropoietin content. The results showed that compared with those in the control group (C group), the flora and metabolites in the hypoxemia group (D group) were altered. We found alterations in the flora according to the metabolic marker tyrosine through random forest and ROC analyses. Fecal and serum metabonomics analyses revealed that microbial metabolites could be absorbed into the blood and participate in human metabolism. Finally, a significant correlation between tyrosine and erythropoietin (EPO) content was found, which shows that human intestinal flora and its metabolites can help to confront altitude stress by regulating EPO levels. Our findings provide new insights into the adaptive mechanism and prevention of AHAH.

Quantifying systemic molecular networks affected during high altitude de-acclimatization

High altitude acclimatization and disease have been the centerpiece of investigations concerning human health at high altitude. Almost all investigations have focused on either understanding and ameliorating high altitude disease or finding better methods of acclimatization/training at high altitude. The aspect of altitude de-induction/de-acclimatization has remained clouded despite the fact that it was documented since the first decade of twentieth century. A few recent studies, particularly in China, have stated unanimously that high altitude de-acclimatization involved multiple observable clinical symptoms ranging from headache to abdominal distention. These symptoms have been collectively referred to as “high altitude de-acclimatization syndrome” (HADAS). However, computational omics and network biology centric investigations concerning HADAS are nascent. In this study, we focus on the quantitative proteo-informatics, especially network biology, of human plasma proteome in individuals who successfully descended from high altitude areas after a stay of 120 days. In brief, the protein list was uploaded into STRING and IPA to compute z-score based cut-offs which were used to analyze the directionality and significance of various identified protein networks as well as the proteins within them. Relevant upstream regulators extracted using computational strategies were also validated. Time-points till the 180th day of de-induction have been investigated to comparatively assess the changes in the plasma proteome and protein pathways of such individuals since the 7th day of arrival at altitude. Our investigation revealed extensive effects of de-induction on lipid metabolism, inflammation and innate immune system as well as coagulation system. This novel study provides a conceptual framework for formulating therapeutic strategies to ease the symptoms of HADAS during de-acclimatization. Such strategies should focus on normalization of lipid metabolism, inflammatory signaling and coagulation systems.