Xie, Weiwei, Xianli Wu, Yiding Li, Qing Xiang, Na Wu, Haolun Sun, Bianba Duojie, Hongda Zhao, Jun Liang, and Ye Fan. Erythrocytapheresis Improves Health-Related Quality of Life in High-Altitude Migrans with Chronic Mountain Sickness: A Single-Arm Before-After Trial at 4,000-4,500 m. High Alt Med Biol. 00:00-00, 2026.Chronic mountain sickness (CMS) arises from maladaptive responses to prolonged residence at altitudes exceeding 2,500 m. Despite the known efficacy of erythrocytapheresis on CMS, the impact of this intervention on health-related quality of life for individuals diagnosed with CMS remains poorly understood. We conducted a single-arm before-after trial using erythrocytapheresis on a total of 22 male migrants with CMS who had resided at high altitudes (4,000-4,500 m) for 6.5 (3.8, 9.3) years. Participants underwent between 1 and 4 erythrocytapheresis sessions, with 1-2 days between each one. The participants exhibited significant improvements following the intervention: health-related quality of life score increased from 85.0 (80.0, 85.3) to 90.0 (90.0, 94.3) (p < 0.001, d = 0.57); CMS score decreased from 7.0 (6.0, 8.0) to 3.0 (2.8, 4.0) (p < 0.0001, d = 0.62); the distance in the 6-Minute Walk Test improved from 612.5 (598.8, 623.0) meters to 654.0 (636.3, 676.3) meters (p < 0.0001, d = 0.62); and SpO2 levels rose from 87.5 (85.8, 90.0) to 90.0 (87.0, 92.5) (p = 0.012, d = 0.38). Erythrocytapheresis proves to be an effective intervention for enhancing health-related quality of life and reducing the severity of CMS in migrant populations.
Buja, Alessandra, Sandro Cinquetti, Marco Coller, Angela Padoin, Chiara Trevisiol, Ilaria Pantaleo, Claudio Palmeri, Vincenzo Marcotrigiano, Erica Bino, Silvia Flesia, and Simone Mocellin. Health promotion for sun protection: a community approach in a mountain setting. High Alt Med Biol. 00:00-00, 2026. OBJECTIVE:Alpine regions exhibit high incidence rates of cutaneous melanoma due to increased ultraviolet radiation at higher altitudes. In 2022, the "Montagna SÌ, Melanoma NO" (Mountain YES, Melanoma NO) public health campaign began promoting sun-protective behaviors in these areas. This study aims to evaluate an intervention's effectiveness 3 years after its launch and assess improvements in sun safety practices. METHODS:A before-and-after comparative study was conducted by surveying a random sample of 229 Belluno residents in the Veneto Region, Italy, in 2022, and 115 of those same individuals in 2025 using a standardized questionnaire. Data on sociodemographics, phenotypic characteristics, sun exposure habits, sunscreen use, protective clothing/eyewear usage, and campaign awareness were collected. RESULTS:In 2025, 43% of respondents (95% CI: 33.44%-52.17%) reported being aware of the health promotion efforts. A significant increase in sunscreen application during outdoor activities lasting more than 1 hour and during skiing was detected. Nevertheless, other protective measures, such as the use of caps and sunglasses, did not demonstrate any significant improvement. CONCLUSIONS:The campaign was effective. It reached its target population and improved sun-protective behaviors, confirming the value of community-engaged, tailored health promotion strategies. Further initiatives are necessary to address the remaining gaps in melanoma prevention adherence.
Kolokas, Iraklis, Jenny Schlichtiger, Sara Jamali, Lina Kronschnabel, Paul Adam, Jeremias Götschke, Pontus Mertsch, Christian Goelz, Solveig Vieluf, and Stefan Brunner. Exercise-induced autonomic and cardio-respiratory stress at high altitude in leisure athletes. High Alt Med Biol. 00:00-00, 2026. BACKGROUND:Exercise at high altitude imposes additional cardiovascular and autonomic demands on leisure athletes. We investigated how acute exposure to high altitude alters cardiovascular, respiratory, and autonomic regulation during rest, exercise start, and peak exercise. METHODS:Briefly, 12 nonacclimatized participants (five female) performed standardized exercise tests at low and high altitude, while heart rate (HR), respiratory rate (RR), heart rate variability (HRV_RMSSD), respiratory rate variability (RRV_RMSSD), and respiratory sinus arrhythmia (RSA) were measured using wearable electrocardiogram (ECG) recordings and computer-based signal analysis. RESULTS:Maximal power output during the maximal incremental cycling test was lower at high altitude (235.5 ± 65.5 W) compared to low altitude (276.4 ± 77.5 W). HR and RR increased with exercise intensity and showed a nonsignificant increase at high altitude. RMSSD decreased during exercise (-116.67 ± 79.29 ms, p < 0.01) and at high altitude (-50.16 ± 91.55 ms, p = 0.015), with a significant interaction during exercise at high altitude (p < 0.01), while RRV remained relatively stable. RSA was reduced at high altitude (-1.1 ± 0.71 bpm, p = 0.028) and during exercise (-4.37 ± 0.38 bpm, p < 0.01), reflecting lower cardio-respiratory coupling. CONCLUSION:These patterns indicate that acute high-altitude exercise shifts autonomic balance, imposing heightened cardiac strain while the respiratory system maintains adaptive ventilatory flexibility, highlighting their differential roles in supporting oxygen delivery and systemic homeostasis under hypoxic stress.
Chen, Biao, Shuai Li, Kun He, Dunzhu Basang, Yuzhen Suolang, Fang Li, Jiangcun Silang, Hongyuan Yi, Langjie Jinmei, La Dan, Deqing Ciren, Haifeng Xu, and Dong Wu. Mitigating Intraoperative Fatigue in Surgeons at High Altitude: A Stepped-Wedge Cluster Randomized Trial. High Alt Med Biol. 00:00-00, 2026. BACKGROUND:Both genetically adapted Tibetan surgeons and less-acclimatized Han surgeons deployed through the Aid-Tibet medical aid program face significant challenges from hypobaric hypoxia in the Qinghai-Xizang Plateau. Hypoxia is known to impair cognitive functions and induce fatigue, threatening surgical performance and patient safety. Traditionally, surgeons in Tibet consume Coca-Cola to combat fatigue, a potentially harmful practice lacking in scientific basis. Supplemental oxygen, recommended for better cerebral oxygen delivery, is underutilized. This study compares supplemental oxygen versus Coca-Cola in mitigating intraoperative fatigue among surgeons in Tibet, considering the influence of long-term high-altitude adaptations. METHODS:We conducted a stepped-wedge cluster randomized controlled trial at the People's Hospital of Xizang Autonomous Region in Lhasa (3,650 m altitude). Twenty-two surgeons (11 Han, 11 Tibetan) performed 24 surgeries each, receiving either 100 ml of Coca-Cola every 30 minutes or continuous 2 l/min supplemental oxygen via nasal cannula. Cognitive fatigue was assessed using the d2 Test of Attention, and physical fatigue was measured using a dynamometer, before and after surgeries. The primary outcome was change in concentration performance (ΔCP). The secondary outcome was the change in maximum voluntary contraction force (ΔMVC). Data were analyzed using a linear generalized estimating equations model. RESULTS:All 22 surgeons completed 528 surgeries. Generally, supplemental oxygen significantly reduced cognitive fatigue compared to Coca-Cola (ΔCP: 6.08, 95% confidence interval [CI]: 1.37-10.80, p = 0.012). In subgroup analysis, oxygen significantly lowered cognitive fatigue in Han surgeons (ΔCP: 7.06, 95% CI: 0.72-13.40, p = 0.029), while the effect in Tibetan surgeons did not reach statistical significance (ΔCP: 4.82, 95% CI: -0.51-10.16, p = 0.076). No significant difference was observed in physical fatigue (ΔMVC: -0.18, 95% CI: -1.77-1.40, p = 0.822). CONCLUSIONS:Supplemental oxygen outperforms Coca-Cola in reducing cognitive fatigue during high-altitude surgery, especially for less-acclimatized Han surgeons, supporting its adoption to enhance surgeons' performance and well-being.
Zhuoga Danzeng, Luobu Gesang, Yangzong Suona, Yuansheng Wang, Yangjin Baima, Bai Ci, Ju Huang, Zhuoma Ciren, Rui Zhang, Binyun Liu, and Quzong Zhaxi. Establishing Early Intervention Thresholds for High-Altitude Polycythemia: Evidence from a Cross-Sectional Study of Tibetan Residents. High Alt Med Biol. 00:00-00, 2026. BACKGROUND:High-altitude polycythemia (HAPC), defined by elevated hemoglobin levels, is a key feature of chronic mountain sickness, yet the "intermediate zone" preceding overt HAPC remains poorly understood. This cross-sectional study aimed to define evidence-based thresholds for early intervention in high-altitude populations. METHODS:A total of 2,819 indigenous Tibetan residents (≥18 years) living at altitudes ≥ 4,500 m were classified into three groups based on hemoglobin levels: normal (males: 130-175 g/l; females: 115-150 g/l), intermediate (males: 175-210 g/l; females: 150-190 g/l), and HAPC (males: ≥210 g/l; females: ≥190 g/l). We assessed clinical phenotypes, organ function, and metabolic parameters through questionnaires, physical exams, biochemical analyses, and echocardiography. Logistic regression identified health risks for each group. RESULTS:Revealed that participants in the intermediate and HAPC groups exhibited significant abnormalities compared with the normal group: increased waist circumference (p < 0.001), elevated low-density lipoprotein cholesterol (LDL-C; p < 0.001), and higher uric acid levels (p < 0.001), with an increased risk of hyperuricemia (OR = 2.077, p < 0.001). Additionally, SpO2 was lower in the intermediate (83%) and HAPC (80%) groups, indicating worsening hypoxia (p < 0.001). Organ function abnormalities included elevated ALT levels (p < 0.001) and right ventricular wall thickness (p = 0.025). CONCLUSION:These findings suggest that individuals in the intermediate zone exhibit early signs of organ dysfunction, indicating a "pre-HAPC state." We advocate for a risk-stratified approach to early intervention in high-altitude illness.
Chen, Yanli, Suying Zhu, Doudou Hao, Zhiyou Shi, Yang Zhong, Suyuan Wang, and Yunhong Wu. Time-Dependent Effects of Chronic Hypoxic Exposure on Microarchitecture of Different Skeletal Sites in Mice. High Alt Med Biol. 00:00-00, 2026.-High-altitude hypoxia accelerates bone loss by disrupting bone metabolic homeostasis. Currently, hypoxic effects on bone and their link to exposure time remain undefined. This study aimed to systematically evaluate the dynamic effects of chronic hypoxic exposure on bone homeostasis and bone microstructure in different skeletal sites through in vivo and in vitro experiments. Male C57BL/6J mice were exposed to 5,500 m simulated hypoxia for 16 weeks. Micro-CT analyzed cervical (C3-C4), lumbar (L4-L6) vertebrae, and femurs. Histopathological analysis assessed bone tissue and multiorgan pathology. In vitro experiments, a 5% hypoxic culture system was established to detect the proliferation and differentiation capabilities of MC3T3-E1 osteoblasts. After 12 weeks of hypoxic exposure, compared with the control group, the trabecular separation (Tb.Sp) of the mouse femur was significantly increased, and the bone mineral content was significantly decreased. After 16 weeks of exposure, the trabecular bone volume/tissue volume (Tb.BV/TV) and bone mineral density of the cervical vertebrae, lumbar vertebrae, and femurs were significantly reduced. H&E staining showed osteoblasts in multiple bones of hypoxic mice shifted to quiescent states, and long-term hypoxia induced multi-organ damage (pulmonary, renal, colonic, skeletal muscle). 5% hypoxia significantly downregulated collagen type I and alkaline phosphatase (ALP) mRNA levels in MC3T3-E1 cells, inhibited ALP activity and mineralized nodule formation, and reduced osteoblast differentiation capacity. Chronic hypoxic exposure induces bone loss in multiple skeletal sites of mice in a time-dependent manner, with femur showing significantly higher sensitivity to hypoxic exposure than the cervical and lumbar vertebrae. The underlying mechanism may be related to hypoxia inhibiting osteoblast function and disrupting the balance of bone metabolism. Long-term hypoxia also causes pathological damage to multiple organs. This study provides evidence for clarification of the pathological mechanism of hypoxic bone injury and lays a foundation for the subsequent development of targeted intervention strategies for hypoxia-related bone diseases.
Pena, Eduardo, Samia El Alam, Juliane Hannemann, and Rainer Böger. Compliance and genetic variability are determinants of the success of l-arginine/l-citrulline supplementation in high altitude-A pilot study. High Alt Med Biol. 00:00-00, 2026. BACKGROUND:Asymmetric dimethylarginine (ADMA) is a risk biomarker of high-altitude pulmonary hypertension (HAPH). ADMA is inactivated by dimethylarginine dimethylaminohydrolase (DDAH)1 and 2. Single nucleotide polymorphisms in these genes contribute to genetic predisposition for HAPH. Supplementation with l-arginine may reverse ADMA's inhibitory effect and, thus, HAPH. We conducted a pilot study to test whether supplementation with l-arginine/l-citrulline (A/C) during chronic intermittent hypoxia (CIH) limits the increase in pulmonary arterial pressure (PAP) as compared to placebo. METHODS:Twenty male volunteers were randomly assigned to receive 6 months of A/C or placebo; PAP was assessed by echocardiography. RESULTS:l-Arginine increased in the A/C group at month 1, which subsided until month 6 due to poor compliance with the study supplement. Individuals with 2 or more alleles of a previously described DDAH1/2 haplotype showed a higher increase in ADMA during CIH. A/C caused a trend toward a diminished increase in PAP. However, these findings should be interpreted as exploratory, consistent with the low adherence to treatment in this pilot study. The increase in l-arginine blood levels was attenuated in carriers of a previously described ARG1/2 haplotype. CONCLUSION:Our data show that A/C supplementation may offer an opportunity to alleviate the altitude-induced increase in PAP; however, long-term compliance and genetic factors may affect outcome.
Villamonte-Calanche, Wilfredo, Marco Antonio Salazar-Zegarra, Franklin Miranda-Solis, and María Jerí-Palomino. Correlation of uterine blood flow in the first trimester of pregnancy and birth weight at term in high altitude. High Alt Med Biol. 00:00-00, 2026. OBJECTIVE:To determine the correlation between total uterine artery flow (UtAQ) at the end of the first trimester of pregnancy and birth weight (BW) at term at 3,400 m altitude. METHODS:Prospective study, conducted at 3,400 m altitude in 210 women who underwent routine ultrasound evaluation. The inclusion criteria were singleton pregnancy between 11 and 14 weeks + 1 day, crown-rump length between 45 and 84 mm, born and raised at high altitude (native), and without pathology. The outcome was BW, expressed as a Z score. Variables such as UtAQ, uterine artery (UtA) diameters, age, body mass index, and mean arterial pressure, among others, were evaluated. RESULTS:After applying the inclusion criteria, 203 pregnant women were evaluated, out of a total of 210 women. The average diameter of UtA was 0.27 cm, and the total bilateral UtA blood flow was 305.8 ml/min. A significant correlation was found between BW and UtAQ (rho = 0.15, p = 0.033), with a higher association for the left UtA (rho = 0.19, p = 0.007). Similarly, BW was positively correlated with the average diameter of the UtAs (r = 0.21, p = 0.003) and the association was stonger for the left UtA (r = 0.19, p = 0.006). CONCLUSION:In low-risk singleton pregnancies among native women living at high altitude, a correlation was observed between UtAQ and term BW, with the highest association found between BW and the diameter and UtAQ of the left UtA.
Brillhart, Aaron, Molly Enenbach, Javier Seufferheld, Bernabé Abramor, Peter Callas, Rodrigo Duplessis, Ian Guertin, Theodore A Hartridge, Roxana Pronce, Ana Saravia, and Scott E. McIntosh. Medical screening of climbers who later develop high-altitude pulmonary edema on Aconcagua. High Alt Med Biol. 00:00-00, 2026. INTRODUCTION:On Aconcagua (6,961 m), high-altitude pulmonary edema (HAPE) is the most frequent reason for medical evacuation. This study aimed to compare medical screening data of climbers who developed HAPE with those who did not and to identify trends to aid in illness prevention and climber safety. METHODS:De-identified medical screening data of Aconcagua climbers from 2024 to 25 were retrospectively reviewed, comparing climbers who developed HAPE with those who did not. RESULTS:Fifty-three of 2,336 climbers developed HAPE (2.3%). Asymptomatic climbers screened at 4,300 m who later developed HAPE had lower mean oxygen saturation than controls (80% vs. 85%, p < 0.001) and higher mean heart rate (96 vs. 87 bpm, p < 0.001). Nonsignificant trends were noted with guided status (74% vs. 61%, p = 0.06), and prophylactic acetazolamide use (34% vs. 21%, unadjusted: p = 0.02, odds ratio [OR] 1.92, adjusted: p = 0.08, OR 1.74). CONCLUSIONS:On Aconcagua, certain vital sign parameters, including oxygen saturation below 80% and tachycardia during asymptomatic screening at 4,300 m, could raise concern for later developing HAPE. Future research could clarify any association between HAPE, certain climber groups such as guided clients, ascent rate, and medication use. Gradual ascent should continue to be emphasized to facilitate acclimatization and prevent life-threatening altitude illness such as HAPE.
Ferrarini, Giovanni, Mattia Canevari, Valeria Azzini, Piergiuseppe Agostoni, Beatrice Pezzuto, and Carlo Vignati. Physiological responses to acute hypobaric and normobaric hypoxia: Differences in maximal exercise and clinical impact. High Alt Med Biol. 00:00-00, 2026.-Hypoxia, defined by inspired partial pressure of oxygen (PiO2) <150 mmHg, has been extensively studied in conditions of both reduced barometric pressure (hypobaric hypoxia, HH) and reduced inspired fraction of oxygen (FiO2) at sea level (normobaric hypoxia, NH). Traditionally considered interchangeable, mounting evidence indicates that HH and NH elicit distinct cardiovascular, ventilatory, and gas-exchange responses during physical effort, likely due to factors beyond PiO2, including air density, alveolar gas composition, exercise modality, and the age and sex of the individual performing the effort. A thorough understanding of how different hypoxic modalities affect exercise responses provides fundamental insights into human physiology and pathophysiology under extreme conditions, with practical implications for sports medicine and athletic training, as well as for patients with pathologies potentially influenced by hypoxia dealing with high altitude. This narrative review synthesizes current evidence on the differential effects of HH and NH on exercise responses, with an emphasis on maximal exercise capacity and underlying the physiological mechanisms regarding cardiovascular function, ventilatory adaptation, and gas-exchange responses, also outlining the implications for athletes, clinical populations (heart failure, chronic obstructive pulmonary disease, pulmonary hypertension), and altitude medicine.
Hill, Adam D. Slow symptom resolution of acute altitude illness upon rapid descent. High Alt Med Biol. 00:00-00, 2026.-Acute mountain sickness (AMS) effects roughly one-quarter to more than three-quarters of persons travelling to elevations greater than 2,500 m. Treatment relies primarily on descent or a stoppage of further ascent (with or without pharmacologic therapy) to allow for acclimatization. In the latter approach, acclimatization as heralded by improvement of symptoms can take anywhere from 12 hours to 4 days. The timeline for symptom resolution when descent takes place, however, is not clearly defined. A case is presented of a hiker who suffered from persistent symptoms of AMS for nearly 24 hours despite descending rapidly to sea level.
Ramírez, Esteban, C Alejandro Luzardo, Daniel F Namen, Juan D Rivera, Lina Pérez, Daniela Mora, Nicolás Moncada, Santiago Lopez, and Jaime Guiza. Heart rate variability in adults from low- and high-altitude origins residing in a high-altitude city: A cross-sectional comparison. High Alt Med Biol. 00:00-00, 2026. BACKGROUND:Heart rate variability (HRV) is used to assess autonomic regulation, reflecting autonomic nervous system activity through heartbeat interval analysis. HRV can be evaluated using time-domain, frequency-domain, and nonlinear methods. Although acute high-altitude exposure has been studied, the effects of chronic exposure remain less well understood. METHODS:This study compared HRV in adults from altitudes ≥2,500 m (group 1) and <1,500 m (group 2), with both groups residing in Bogotá, Colombia (2,600 m) for more than 6 months. HRV was assessed using time domain, frequency domain, and nonlinear metrics. RESULTS:Participants from low-altitude regions (group 2) exhibited higher resting heart rates (p = 0.002) and lower time domains (standard deviation of normal-to-normal intervals, root mean square of successive differences, number of pairs of successive normal-to-normal intervals differing by more than 50 ms, percentage of NN50 [%]; p < 0.05), frequency domain (total power, high-frequency power; p ≤ 0.004), and nonlinear measures (triangular interpolation of the NN interval histogram, standard deviation of instantaneous beat-to-beat variability, short-term fractal scaling exponent; p < 0.05) than those from high-altitude regions. These results indicate a lower HRV in individuals from low-altitude regions. CONCLUSION:Adults raised at low altitudes showed lower HRV when living in Bogotá compared with those raised at high altitudes, suggesting an association with long-term autonomic differences potentially related to early-life altitude exposure, rather than a direct causal effect of chronic hypoxia during childhood. These findings may have physiological and clinical implications, particularly in countries with diverse geography. Further prospective, longitudinal research is needed to confirm these associations and clarify their cardiovascular relevance and the potential contribution of genetic and environmental factors.
BACKGROUND:This study examined the effects of chronic high-altitude hypoxic exposure on attention networks in indigenous primary school students, integrating cardiovascular indices to explore underlying physiological mechanisms. METHODS:Three real-world altitude groups were established: low (2,200 m), mid (3,200 m), and high (4,200 m). Cardiovascular function was assessed via systolic blood pressure, diastolic blood pressure, and heart rate. Attentional performance was evaluated using the Attention Network Test (ANT), which provides measures of alerting, orienting, and executive control efficiency. RESULTS:Cardiovascular indices followed a nonlinear pattern across altitudes, with systolic blood pressure, diastolic blood pressure, and heart rate being significantly higher at mid-altitude compared to both low and high altitudes. In contrast, attention performance exhibited an opposite trend: alerting and executive control efficiency were relatively reduced at mid-altitude but were comparable between the low- and high-altitude groups. Orienting efficiency did not differ significantly across the three altitude groups. CONCLUSIONS:The findings reveal a dissociation between physiological regulation and cognitive performance under chronic hypoxia. To explain these results, we propose a U-shaped model of cardiovascular adaptation, where mid-altitude represents an incomplete compensatory state, while prolonged exposure at higher altitudes leads to stabilized cardiovascular function and preserved attentional performance. This integrative framework underscores the crucial role of physiological adaptation in shaping cognitive outcomes in high-altitude environments.
