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. 00:00-00, 2024. 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.

Szymczak, Robert K., Magdalena Sawicka, and Małgorzata Jelitto. Recurrent pulmonary embolism at high altitude in a mountaineer with hereditary thrombophilia. High Alt Med Biol. 25:345-347, 2024.-It is speculated that high-altitude travel is an independent risk factor for thrombosis. Mountaineering-specific factors, such as hypoxia, cold, and immobilization, may interact with patient-specific risk factors and contribute to thrombus formation. We present the case of a mountaineer with hereditary thrombophilia who experienced recurrent pulmonary embolism during high-altitude expeditions.

Ebert-Santos, Christine, and Ana Campos. Ileus at altitude. High Alt Med Biol. 25:342-344, 2024.-Autoimmune myasthenia gravis (MG) is a condition commonly caused by the production of antibodies that block acetylcholine receptors. Until recently, gastrointestinal (GI) symptoms were considered rare in myasthenia gravis, but are now being proposed as an early identification tool. Presented here is a case study that exemplifies GI symptoms in MG, exacerbated by low barometric pressure at altitude. This illustrates the need to identify GI symptoms earlier in MG patients, as well as the need for providers at high altitude to be aware of these manifestations of MG.

Berkemeier, Quint N., Michael R. Deyhle, James J. McCormick, Kurt A. Escobar, and Christine M. Mermier. The potential interplay between HIF-1α, angiogenic, and autophagic signaling during intermittent hypoxic exposure and exercise High Alt Med Biol. 25:326-336, 2024.-Environmental hypoxia as a result of decreased barometric pressure upon ascent to high altitudes (>2,500 m) presents increased physiological demands compared with low altitudes, or normoxic environments. Competitive athletes, mountaineers, wildland firefighters, military personnel, miners, and outdoor enthusiasts commonly participate in, or are exposed to, forms of exercise or physical labor at moderate to high altitudes. However, the majority of research on intermittent hypoxic exposure is centered around hematological markers, and the skeletal muscle cellular responses to exercise in hypoxic environments remain largely unknown. Two processes that may be integral for the maintenance of cellular health in skeletal muscle include angiogenesis, or the formation of new blood vessels from preexisting vasculature and autophagy, a process that removes and recycles damaged and dysfunctional cellular material in the lysosome. The purpose of this review is to is to examine the current body of literature and highlight the potential interplay between low-oxygen-sensing pathways, angiogenesis, and autophagy during acute and prolonged intermittent hypoxic exposure in conjunction with exercise. The views expressed in this paper are those of the authors and do not reflect the official policy of the Department of Army, DOD, DOE, ORAU/ORISE or U.S. Government.

Luks, Andrew M., Thomas G. DeLoughery, Jeffrey H. Gertsch, and Suzy Stokes. Clinical conundrum: return to high altitude after cerebral venous sinus thrombosis. High Alt Med Biol. 25:337-341, 2024.

Wang, Liping, Gang Fu, Ruijuan Han, Peijia Fan, Jing Yang, Kerui Gong, Zhijun Zhao, Chunyang Zhang, Kai Sun, and Guo Shao. MALAT1 and NEAT1 are neuroprotective during hypoxic preconditioning in the mouse hippocampus possibly by regulation of NR2B. High Alt Med Biol. 25:285-294, 2024. Background: The regulation of noncoding ribonucleic acid (ncRNA) has been shown to be involved in cellular and molecular responses to hypoxic preconditioning (HPC), a situation created by the induction of sublethal hypoxia in the brain. The ncRNAs metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) and nuclear paraspeckle assembly transcript 1 (NEAT1) are abundantly expressed in the brain, where they regulate the expression of various genes in nerve cells. However, the exact roles of MALAT1 and NEAT1 in HPC are not fully understood. Methods: A mouse model of acute repeated hypoxia was used as a model of HPC, and MALAT1 and NEAT1 levels in the hippocampus were measured using real-time polymerase chain reaction (PCR). The mRNA and protein levels of N-methyl-d-aspartate receptor subunit 2 B (NR2B) in the mouse hippocampus were measured using real-time PCR and western blotting, respectively. HT22 cells knocked-down for MALAT1 and NEAT1 were used for in vitro testing. Expression of NR2B, which is involved in nerve cell injury under ischemic and hypoxic conditions, was also evaluated. The levels of spectrin and cleaved caspase-3 in MALAT1 and NEAT1 knockdown HT22 cells under oxygen glucose deprivation/reperfusion (OGD/R) were determined by western blotting. Results: HPC increased the expression of MALAT1 and NEAT1 and decreased the expression of NR2B mRNA in the mouse hippocampus (p < 0.05). Knockdown of MALAT1 and NEAT1 increased both NR2B mRNA and protein levels nearly twofold and caused damage under OGD/R conditions in HT22 cells (p < 0.05). Conclusion: MALAT1 and NEAT1 exert neuroprotective effects by influencing the expression of NR2B.

González-García, Mauricio and Luis Ernesto Téllez. Adaptation to living at high altitude in patients with COPD. Comparative study of exercise capacity and ventilatory variables between patients residing at high and low altitudes in the Andes. High Alt Med Biol. 25:266-273, 2024. Introduction: Although some variables related to oxygen transport and utilization such as ventilation, pulmonary vascular responses to hypoxia, heart rate (HR), cardiac output, hemoglobin (Hb), and oxygen saturation (SpO₂) are used to compare adaptation to altitude between populations, peak oxygen consumption (VO₂) constitutes an integrative measure of total oxygen transport that may reflect successful adaptation to altitude. We designed this study to make a direct comparison of VO₂ in a cardiopulmonary exercise test (CPET) between chronic obstructive pulmonary disease (COPD) patients residing at high altitude (Bogotá, Colombia: 2,640 m) (COPD-HA) and those living at low altitude (Bucaramanga, Colombia: 959 m) (COPD-LA). Methods: All patients performed a CPET with measurements of VO₂, minute ventilation (V_E), HR, oxygen pulse (VO₂/HR), ventilatory equivalents (V_E/VCO₂), and SpO₂. Unpaired T-test or Mann-Whitney U test were used for comparisons between COPD-HA and COPD-LA. Results: We included 71 patients with COPD, 53 COPD-HA, and 18 COPD-LA. There were no differences between groups in age, sex, or forced expiratory volume in 1 second. The means ± SD of Hb, g/dl was slightly higher in COPD-HA (15.9 ± 1.9 vs. 14.7 ± 1.8, p = 0.048), without differences in VO₂, % pred (71.6 ± 17.9 vs. 69.0 ± 17.0, p = 0.584), VO₂/HR, % pred (92.1 ± 22.0 vs. 89.7 ± 19.8, p = 0.733) or V_E/MVV, % (75.5 ± 14.1 vs. 76.5 ± 14.3, p = 0.790) at peak exercise between groups. Median (IQR) of V_E/VCO₂ nadir [38.0 (37.0-42.0) vs. 32.5 (31.0-39.0), p = 0.005] was significantly higher, and SpO₂, % at rest [88.0 (86.0-91.0) vs. 95.0 (94.0-96.0), p < 0.001] and at peak exercise [84.0 (77.0-90.0) vs. 93.0 (92.0-95.0), p < 0.001] were significantly lower in COPD-HA. Conclusions: Despite higher desaturation at rest and during exercise in COPD-HA, there were no differences in VO₂ peak between COPD-HA and COPD-LA, suggesting a potential altitude adaptation in those patients chronically exposed to hypoxia.

Ortiz-Prado, Esteban, Juan Sebastian Izquierdo-Condoy, María G. Dávila-Rosero, Jorge Vásconez-González, Ana M. Diaz, Carla E. Moyano, Vanessa Arcos-Valle, Ginés Viscor, and Joshua H. West. Reduced violence-related burden and mortality at higher altitudes: examining the association between high altitude living and homicide rates in Ecuador. High Alt Med Biol. 25:295-307, 2024. Background: Homicides are a major public health concern and a leading cause of preventable deaths worldwide. The relationship between altitude and homicides remains unclear, and evidence of the possible effects of living at high altitudes on homicide rates is limited. This research aimed to investigate the mortality rates resulting from various types of aggression that culminated in homicides in Ecuador and to explore potential differences associated with altitude. Methods: An ecological analysis of homicide rates in Ecuador was conducted from 2001 to 2022. Homicide cases and the population at risk were categorized based on their place of residence according to two altitude classifications: a binary classification of low (<2,500 m) and high altitude (>2,500 m), and a detailed classification according to criteria by the International Society for Mountain Medicine, which includes low (<1,500 m), moderate (1,500-2,500 m), high (2,500-3,500 m), and very high altitude (3,500-5,500 m) categories. Both crude and directly age-sex standardized mortality rates were calculated for each altitude category. Results: We analyzed a total of 40,708 deaths attributed to aggressions (ICD-10 codes X85-Y09). The total homicide rate for men was 21.29 per 100,000 (95% confidence interval [CI]: 9.55-32.37), whereas for women, it was 2.46 per 100,000 (95% CI: 1.44-3.27). Average rates across the 22 analyzed years were higher at low altitudes (men: 13.2/100,000 and women: 1.33/100,000) as compared with high altitudes (men: 5.79/100,000 and women: 1.05/100,000). Notably, the male-to-female rate difference was more pronounced at low altitudes (898%) than at high altitudes (451%). Conclusions: Our study revealed a higher prevalence of homicides in certain provinces and significant disparities in mortality rates between men and women. Although we cannot establish a direct relationship between altitude and homicide rates, further research is needed to explore potential confounding factors and a better understanding of the underlying causes for these variations.