High altitude medicine & biology最新文献

Guo, Yan, Chao Yu, Zhongsheng Lu, Menglan Zhang, Qiang Zhang, and Xiao Liu. Zinc homeostasis plays important roles in hypoxia tolerance: a study conducted clinically and in vitro. High Alt Med Biol. 26:242-255, 2025. Objective: High-altitude environments pose significant challenges to human physiology due to reduced oxygen availability, often resulting in altitude-related illnesses such as high-altitude cerebral edema (HACE). This study focuses on understanding the role of zinc homeostasis in enhancing hypoxia tolerance, which may be pivotal in mitigating the adverse effects of such illnesses. Methods: The study involved healthy individuals from high-altitude (4,500-5,000 m) and low-altitude areas (0-200 m), as well as patients with HACE. Blood samples were collected and analyzed. Additionally, a hypoxic model was developed using human brain microvascular endothelial cells (HBMECs), and zinc intervention was implemented. Results: In the blood samples of patients with HACE and those of healthy individuals, there were over 4,000 differentially expressed genes (DEGs), with more than 300 of them linked to zinc. Among these zinc-associated genes, only carbonic anhydrase I (CA1) exhibited a substantial upregulation in expression, while the expression of others was notably downregulated. Compared with the high-altitude group, hemoglobin (Hb) (14.7 vs. 19.5 g/dl) and plasma zinc (37.0 vs. 94.0 mmol/dl) were lower in HACE, while CA1 (55.4 vs. 8.6 g/l) was elevated (p < 0.01). In vitro studies confirmed that exposure to hypoxia (O₂ 8%-8.5%, 24 hours) inhibited HBMECs proliferation and migration, increased apoptosis and necrosis, and led to abnormal expression of CA1 and various zinc transport proteins. However, zinc intervention (6 μM, 24 hours) significantly mitigated these adverse effects and improved the cell's ability to tolerate hypoxia. Conclusion: Zinc homeostasis was crucial for hypoxia tolerance. Proper zinc supplementation could potentially alleviate symptoms associated with hypoxia intolerance, such as altitude sickness, but further confirmation was needed.

Yin, Jiaojiao, Yuhang Wang, Bing Li, Xiaoyan Hu, Yao Ma, Chong Zhang, Xiaoqin Ha, Linyan Wang, and Yaozhu Pan. Hypobaric hypoxia increased autophagy and apoptosis in PC12 rat pheochromocytoma cells more than normobaric hypoxia. High Alt Med Biol. 26:301-307, 2025. Purpose: Currently, in vitro studies have focused on hypoxia injury in acute mountain sickness (AMS), but little effort has been made to assess the effects of hypobaric hypoxia. AMS is a neurological disorder, and rat pheochromocytoma (PC12) cells are a model to study neuronal survival and apoptosis. Here, we developed a novel cell culture method that mimics hypobaric hypoxia at high attitude and compared the effects of hypobaric hypoxia and normobaric hypoxia on autophagy and apoptosis of PC12 cells. Methods: PC12 cells were cultured under normal conditions, normobaric hypoxia, and hypobaric hypoxia. Autophagy was observed by transmission electron microscopy and immunofluorescence microscopy. The hypoxia-inducible factor1-α (HIF1-α), LC3, caspase-3, and cleaved caspase-3 expression levels were determined by Western blot. Results: The cell culture chamber mimicking hypobaric hypoxia at high attitude perfectly maintained the air pressure at 41.1 kPa and the oxygen density at 1% (PO₂ around 3.08 mmHg). Hypobaric hypoxic treatment of PC12 cells at 0, 4, 8, 16, 24, and 48 hours resulted in an increase in HIF1-α and LC3Ⅱ protein levels, and the ratio of HIF1-α/actin and LC3Ⅱ/actin both peaked at 16 hours (p < 0. 01) when the cell viability was 88.02%. There was a 1.5-fold increase in LC3Ⅱ expression, a 2-fold increase in LC3B-positive spots, and an increase in autophagosome accumulation at hypobaric hypoxia compared to PC12 cells at normobaric hypoxia for 16 hours (p < 0.001). Interestingly, the promotion of autophagy (coculture with rapamycin or 3-MA) in PC12 cells under normobaric hypoxia reduced cleaved caspase-3 expression (the ratio of cleaved caspase-3/caspase-3 decreased, p < 0.01). However, under hypobaric hypoxia, the promotion of autophagy inversely increased cleaved caspase-3 (the ratio of cleaved caspase-3/caspase-3 increased, p < 0.01), and the inhibition of autophagy (hydroxychloroquine [HCQ] coculture) decreased cleaved caspase-3 (the ratio of cleaved caspase-3/caspase-3 decreased, p < 0.01). Conclusions: Compared with normobaric hypoxia cells, hypobaric hypoxia cells cultured in vitro exhibited increased autophagy and apoptosis.

Adams, Edmund and Tamlyn Peel. Chronic mountain sickness: A comprehensive review of current management and proposals for novel therapies. High Alt Med Biol. 26:318-327, 2025.-Chronic mountain sickness (CMS) is an acquired condition affecting 5%-10% of high-altitude residents. Lifelong exposure to chronic hypoxia triggers excessive erythrocytosis, resulting in an expanded hematocrit. Patients present with symptoms such as dyspnea, fatigue, and palpitations. Complications such as pulmonary hypertension and heart failure are often fatal. Relocation to sea level remains the only definitive management of CMS but poses an unacceptable personal burden. Long-term oxygen therapy provides symptomatic relief, but dependency issues remain a concern. Phlebotomy reduces hematocrit and offers short-term symptom relief. However, side effects and cultural conflicts continue to pose challenges. Acetazolamide, enalapril, and medroxyprogesterone have lowered hematocrit and alleviated symptoms in human trials. Further research into systemic side effects, application in women, and long-term use is required. Methylxanthines, adrenergic blockers, almitrine, and dopamine antagonists showed promise in murine and/or short-term human trials, highlighting the need for further long-term human trials. Inhibition of hypoxia-inducible factor and Janus Kinase-signal transducer and activator of transcription pathways is currently used to suppress hematocrit in polycythemia vera, demonstrating potential application in CMS. Topiramate may stimulate ventilation via acid-base modulation, thus providing therapeutic value. Similarly, the effect of aspirin and caffeine on ventilation may provide a low-cost, accessible intervention.

David Eidenbenz, Alexandre Kottmann, Ken Zafren, Pierre-Nicolas Carron, Roland Albrecht, and Mathieu Pasquier. Noncompressible chest wall in critically buried avalanche victims with cardiac arrest: a case series. High Alt Med Biol. 26:129-133, 2025. Introduction: In avalanche victims with cardiac arrest, a noncompressible chest wall or frozen body is a contraindication to initiating cardiopulmonary resuscitation. The evidence sustaining this recommendation is low. Objective: To describe the characteristics and prehospital management of critically buried avalanche victims declared dead on site, with and without noncompressible chest walls. Methods: Retrospective study including all critically buried avalanche victims declared dead on site by physicians of a helicopter emergency medical service in Switzerland, from 2010 to 2019. The primary outcome was the proportion of victims with a noncompressible chest wall reported in medical records. Secondary outcomes included victims' characteristics and the relevance of the criterion, noncompressible chest wall, for management. Results: Among the 53 included victims, 12 (23%) had noncompressible chest walls. Victims with noncompressible chest walls had significantly longer burial durations (median 1,125 vs. 45 minutes; p < 0.001) and lower core temperatures (median 14 vs. 32°C; p = 0.01). The criterion, noncompressible chest wall, assessed in six victims, was decisive for declaring death on site in four victims. Conclusion: The presence of a noncompressible chest wall does not appear to be a sufficient criterion to allow to declare the death of critically buried avalanche victims. Further clinical information should be sought.

Yoder, Taylor L., Kreager A. Taber, Laurens E. Howle, and Richard E. Moon. Pushing scuba to new heights: approach, decompression, and logistical considerations for high-altitude diving. High Alt Med Biol. 26:109-117, 2025.-There is interest among technical, expedition, commercial, and military divers in expanding diving operations to high altitude. However, altitude diving presents unique challenges including acclimatization, increased decompression sickness (DCS) risk, and logistical and equipment considerations. Divers must plan altitude acclimatization strategies conservatively to reduce risk of acute mountain sickness and dehydration before diving. Several methods of augmenting sea level diving tables to be used at altitude have been theorized and tested both in simulated dives and high-altitude expeditions. With proper acclimatization, augmentation of standard diving tables, equipment, and safety planning, diving at high altitude may be performed in many contexts safely while minimizing risk of DCS or injury.

Sharma, Narendra Kumar, Mansi Srivastava, Tikam Chand Dakal, Vipin Ranga, and Pawan Kumar Maurya. Acute hypobaric hypoxia causes alterations in acetylcholine-mediated signaling through varying expression of muscarinic receptors in the prefrontal cortex and cerebellum of rats' brain. High Alt Med Biol. 26:156-164, 2025. Background: Muscarinic receptor (CHRM) proteins are G-protein-associated acetylcholine receptors found in neuronal membranes. Five major subtypes, CHRM1-CHRM5, modulate acetylcholine in central nervous system signaling cascades. CHRM1, CHRM3, and CHRM5 are linked to Gαq/Gα11 proteins, whereas CHRM2 and CHRM4 are linked to Gαi/Gαo proteins. Objective: Limited research has been conducted to explore the impact of HH on CHRM gene expressions. It is caused by low oxygen availability at high altitudes, which impairs neurotransmission, cognitive performance, and physiological functions. Previous studies have shown that exposure to hypoxia leads to a reduction in CHRM receptors, which in turn causes alteration in signal transduction, physiological responses, cognitive deficits, and mood alterations. Method: In the present study, we have used semiquantitative PCR to measure muscarinic receptor gene expression after 6, 12, and 24 hours of HH exposure at 25,000 feet using a decompression chamber in rat brain's PFC and cerebellum. Result: We have found that CHRM1-CHRM5 downregulated after acute exposure to hypoxia until 12 hours, and then, the expression level of these receptors increased to 24 hours when compared with 12 hours in PFC. All subtypes have shown a similar pattern in PFC regions under hypoxia exposure. On the other hand, these receptors have shown altered expression at different time points in the cerebellum. CHRM1 and CHRM4 acutely downregulated, CHRM2 and CHRM5 downregulated, while CHRM3 upregulated after hypoxia exposure. Conclusion: Our study, for the first time, has shown the altered expressions of muscarinic receptors under temporal hypoxia exposure. The altered expression pattern has shown an association with acclimatization and protection against necrosis due to hypoxia. This study may pave further investigations for understanding and addressing the cognitive, behavioral, and physiological impacts of hypoxia and therapeutic development.

Kansara, Nikunj Kumar, Anurag Timothy, Rijesh Unnithan, and Manas Chatterjee. Unraveling high altitude-induced thromboembolic disorders: polycythemia or complex mechanisms? High Alt Med Biol. 26:204-208, 2024. Background: Thromboembolic disorders (TEDs) occurring at high altitudes due to exposure to hypoxic environments pose a significant challenge for clinicians in high-altitude area. Hypobaric hypoxia often leads to acquired erythrocytosis, which is believed to increase the incidence of thrombosis. This study aims to examine the relationship between thromboembolic events and erythrocytosis. Methodology: A prospective study was conducted, including all the patients admitted to Siachen hospital for TEDs from January 01, 2022, to December 31, 2022. Data on height, duration of the stay, hemoglobin (Hb), and packed cell volume levels at the time of admission were recorded. Results: A total of 35 cases were enrolled during the study period. The average age of the patients was 29.10 years (standard deviation: 6.06). The mean deployment height was 17,300 ft, with a range of 12,000 ft-21,600 ft. The average duration of stay was 73 days, ranging from 7 to 162 days. The mean Hb level was 18 g/dl (SD: 2.64), with a range of 12.4 g/dl-22.4 g/dl. Twenty-five cases of thrombotic events (71.4%) occurred with normal Hb levels (<17.5 mg/dl), compared with 10 cases (28.6%) with Hb levels >17.5 mg/dl. Conclusion: Prolonged stays at high altitudes and exposure to hypobaric hypoxia are major stressors. The study suggests that it is not elevated Hb levels, but rather the body's lack of an appropriate physiological response, that contributes to the development of thromboembolic events.

Häfliger, Alina, Aline Buergin, Laura C. Mayer, Maamed Mademilov, Mona Lichtblau, Talantbek Sooronbaev, Silvia Ulrich, Konrad E. Bloch, and Michael Furian. Sex-specific difference in health-related altitude-effects and their prevention by acetazolamide. Data from a randomized controlled trial. High Alt Med Biol. 26:195-203, 2025. Background: Women are underrepresented in studies on acute mountain sickness (AMS), altitude-induced sleep-disordered breathing and preventive acetazolamide use. Methods: We analyzed sex-specific altitude-effects in participants of a randomized, placebo-controlled, double-blind trial in healthy lowlanders >40 years. Participants took 375 mg/day acetazolamide or placebo starting 24 hours before ascent to and while staying 2 days at 3,100 m. Main outcomes of this analysis were sex-specific incidence of AMS (Lake Louise score ≥3), nocturnal pulse oximetry (SpO₂) and apnea-hypopnea index (AHI) at 3,100 m. Results: With placebo, 30 of 119 (25%) women and 4 of 51 (8%) men developed AMS (p = 0.009 between sexes) at 3,100 m. Among women assigned to placebo, SpO₂ (mean ± SE 84 ± 0%) and AHI (16.9 ± 1.3/h) in night 1 at 3,100 m were lower compared to men (SpO₂ 86 ± 0%; AHI 28.3 ± 1.9/h), despite similar baseline values at 760 m. Mean between-sex difference in altitude-effects (women-men) in SpO₂ was -1.4% (95% CI, -2.4 to -0.3%); AHI -10.7/h (95% CI, -15.7 to -5.7/h). The impact of acetazolamide on AMS was not significant for either sex but acetazolamide improved AHI in men (difference men-women, -9.8/h [95% CI, -16.8 to -2.7/h]). Conclusion: This study suggests sex-specific differences in altitude-induced hypoxemia, periodic breathing, AMS incidence, and in the response to preventive acetazolamide treatment.

Yufei Wang, Qiong Meng, Jin Zhang, Bing Guo, Nanyan Li, Qian Deng, Julinling Hu, Quzong Deji, Han Guan, Wangjiu Danzhen, Hui Yu, Zhifeng Li, and Junmin Zhou. Altitude and metabolic dysfunction-associated fatty liver disease (MAFLD) in China: a population-based study. High Alt Med Biol. 26:148-155, 2025. Objectives: The epidemiological evidence for the relationship between altitude and metabolic dysfunction-associated fatty liver disease (MAFLD) is scarce. This study aims to examine the altitude-MAFLD relationship and explore the potential mediators explaining the relationship. Methods: Data were derived from the China Multi-Ethnic Cohort. The participants' altitude information was extracted from their residential addresses. MAFLD was diagnosed based on radiographically confirmed hepatic steatosis and any one of the following three items: overweight/obese status, diabetes mellitus, or metabolic dysregulation. We performed multivariable logistic regression and mediation analyses to assess the altitude-MAFLD associations and potential mediators, respectively. In the mediation analysis, mediation proportion is an estimate of the extent to which the total effect (altitude-MAFLD association) is accounted for by the pathway through the mediators. Results: In total, 87,679 participants (female: 60.7%, mean age: 51.36 years) were included. The odds ratio of MAFLD was 1.61 (95% confidence interval [CI]: 1.52-1.71) between high and low altitudes, 1.52 (95% CI: 1.43-1.62) between high and middle altitudes, and 1.06 (95% CI: 1.01-1.10) between middle and low altitudes. Of the total estimated effect between high and low altitude, physical activity and vegetable intake accounted for 15.7% (95% CI: 12.8-19.1) and 3.8% (95% CI: 1.2-6.6), respectively. Of the total estimated effect between high and middle altitude, physical activity and vegetable intake accounted for 31.4% (95% CI: 26.2-34.8) and 2.3% (95% CI: 0.6-3.8), respectively. Of the total estimated effect between middle and low altitude, vegetable intake accounted for 11.8% (95% CI: 3.2-61.5). Conclusion: Higher altitude was associated with increased odds of MAFLD, and physical activity and vegetable intake mediated such association. Multifaceted efforts should be taken in public health to promote healthy lifestyles among higher altitude residents.