Recurrent Pulmonary Embolism at High Altitude in a Mountaineer with Hereditary Thrombophilia.

Szymczak, Robert K., Magdalena Sawicka, and Malgorzata Jelitto. Recurrent pulmonary embolism at high altitude in a mountaineer with hereditary thrombophilia. High Alt Med Biol. 00:000-000, 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.

Effects of microplastics on sedimentary greenhouse gas emissions and underlying microbiome-mediated mechanisms: A comparison of sediments from distinct altitudes.

Microplastics (MPs) are emerging contaminants in aquatic ecosystems that can profoundly affect carbon and nitrogen cycling. However, the impact mechanisms of MPs on sedimentary greenhouse gas (GHG) emissions at distinct altitudes remain poorly elucidated. Here, we investigated the effects of polyvinyl chloride (PVC) and polylactic acid (PLA) on sedimentary CO2, CH4, and N2O emissions at distinct altitudes of the Yellow River. PVC increased the relative abundance of denitrifiers (e.g., Xanthobacteriaceae, Rhodocyclaceae) to promote N2O emissions, whereas PLA reduced the abundance of AOA gene and denitrifiers (e.g., Pseudomonadaceae, Sphingomonadaceae), impeding N2O emissions. Both PVC and PLA stimulated the growth of microbes (Saprospiraceae, Aquabacterium, and Desulfuromonadia) associated with complex organics degradation, leading to increased CO2 emissions. Notably, the concurrent inhibition of PLA on mcrA and pmoA genes led to its minimal impact on CH4 emissions. High-altitude MQ sediments, characterized by abundant substrate and a higher abundance of functional genes (AOA, AOB, nirK, mcrA), demonstrated higher GHG emissions. Conversely, lower microbial diversity rendered the low-altitude LJ microbial community more susceptible to PVC, leading to a more significant promotion on GHG emissions. This study unequivocally confirms that MPs exacerbate GHG emissions via microbiome-mediated mechanisms, providing a robust theoretical foundation for microplastic control to mitigate global warming.

The role of oxidative stress and neuroinflammatory mediators in the pathogenesis of high-altitude cerebral edema in rats.

High-altitude environments present extreme conditions characterized by low barometric pressure and oxygen deficiency, which can disrupt brain functioning and cause edema formation. The objective of the present study is to investigate several biomolecule expressions and their role in the development of High Altitude Cerebral Edema in a rat model. Specifically, the study focuses on analyzing the changes in total arginase, nitric oxide, and lipid peroxidation (MDA) levels in the brain following acute hypobaric hypoxic exposure (7620m, SO2=8.1%, for 24hours) along with the histopathological assessment. The histological examination revealed increased TNF-α activity, and an elevated number of mast cells in the brain, mainly in the hippocampus and cerebral cortex. The research findings demonstrated that acute hypobaric hypoxic causes increased levels of apoptotic cells, shrinkage, and swelling of neurons, accompanied by the formation of protein aggregation in the brain parenchyma. Additionally, the level of nitric oxide and MDA was found to have increased (p<0.0001), however, the level of arginase decreased indicating active lipid peroxidation and redox imbalance in the brain. This study provides insights into the pathogenesis of HACE by evaluating some biomolecules that play a pivotal role in the inflammatory response and the redox landscape in the brain. The findings could have significant implications for understanding the neuronal dysfunction and the pathological mechanisms underlying HACE development.

Changes in hypoxic and hypercapnic ventilatory responses at high altitude measured using rebreathing methods.

Ventilatory responses to hypoxia and hypercapnia play a vital role in maintaining gas exchange homeostasis, and in adaptation to high-altitude environments. This study investigates the mechanisms underlying sensitization of hypoxic and hypercapnic ventilatory responses (HVR and HCVR, respectively) in individuals acclimatized to moderate high altitude (3800 m). Thirty-one participants underwent chemoreflex testing using the Duffin modified rebreathing technique. Measures were taken at sea level and after 2 days of acclimatization to high altitude. Ventilatory recruitment thresholds (VRT), HCVR, and HVR were quantified. Acclimatization to high altitude resulted in increased HVR (p<0.001) and HCVR (p<0.001), as expected. We also observed that the decrease in VRT under hypoxic test conditions significantly contributed to the elevated HVR at high altitude since the change in VRT across hyperoxic and hypoxic test conditions was greater at high altitude compared to baseline sea level tests (p=0.043). Pre-VRT ventilation also increased at high altitude (p<0.001), but the change did not differ between oxygen conditions. Taken together, this data suggests that the increase in HVR at high altitude is at least partially driven by a larger decrease in the VRT in hypoxia versus hyperoxia at high altitude compared to sea level. This study highlights the intricacies of respiratory adaptations during acclimatization to moderate high altitude, shedding light on the roles of the VRT, baseline respiratory drive, and two-slope HCVR in this process. These findings contribute to our understanding of how the human respiratory control responds to hypoxic and hypercapnic challenges at high altitude.

A geometric morphometric analysis of wing variations in shape and size of the blue bottle fly, Calliphora vicina (Diptera: Calliphoridae).

A geometric morphometric analysis was performed on the right wing of adult Calliphora vicina (Robineau-Desvoidy) collected across 4 altitudinal levels in Sicily. The objective of this study was to assess differences in shape and centroid size (CS) between females and males and across elevations. The wings analyzed in this study were removed from adults of C. vicina collected with baited traps at 20, 700, 1,153, and 1,552; for this study, 19 landmarks were identified in each wing. The coordinates of the landmarks were aligned and superimposed to prevent variations due to position, orientation, and scale; they were then scaled to the same CS and recentered. CS and Procrustes differences were, respectively, used to assess variations in size and shape. Significant differences were observed in wing shape between males and females but not between all altitudinal levels. Female wings were found to be significantly larger than males (P < 0.01). Wings of flies collected at the highest altitudinal level resulted in significantly larger wings than those collected at lower altitudes (P < 0.001), with CS values ranging from 12.1 to 14.1. Variation in wing shape can impact thermal regulation, and therefore, oxygen content, temperature, atmospheric pressure, and solar radiation can have an effect on an insect's body and activity levels. At high elevations and lower temperatures, larger wings could mean less energy expenditure when flying to increase body temperature.

Symposium review: high altitude travel with pulmonary vascular disease.

Pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension are the main precapillary forms of pulmonary hypertension (PH) summarized as pulmonary vascular diseases (PVD). PVDs are characterized by exertional dyspnoea and oxygen desaturation, and reduced quality of life and survival. Medical therapies improve life expectancy and physical performance of PVD patients, of whom many wish to participate in professional work and recreational activities including traveling to high altitude. The exposure to the hypobaric hypoxic environment of mountain regions incurs the risk of high altitude adverse events (AEHA) due to severe hypoxaemia exacerbating symptoms and further increase in pulmonary artery pressure, which may lead to right heart decompensation. Recent prospective and randomized trials show that altitude-induced hypoxaemia, pulmonary haemodynamic changes and impairment of exercise performance in PVD patients are in the range found in healthy people. The vast majority of optimally treated stable PVD patients who do not require long-term oxygen therapy at low altitude can tolerate short-term exposure to moderate altitudes up to 2500 m. PVD patients that reveal persistent severe resting hypoxaemia ( S p O 2 ${{S}_{{\mathrm{p}}{{{\mathrm{O}}}_{\mathrm{2}}}}}$  <80% for >30 min) at 2500 m respond well to supplemental oxygen therapy. Although there are no accurate predictors for AEHA, PVD patients with unfavourable risk profiles at low altitude, such as higher WHO functional class, lower exercise capacity with more pronounced exercise-induced desaturation and more severely impaired haemodynamics, are at increased risk of AEHA. Therefore, doctors with experience in PVD and high-altitude medicine should counsel PVD patients before any high-altitude sojourn. This review aims to summarize recent literature and clinical recommendations about PVD patients travelling to high altitude.

Tibetans exhibit lower hemoglobin concentration and decreased heart response to hypoxia during poikilocapnia at intermediate altitude relative to Han Chinese.

Background: High-altitude populations exhibit distinct cellular, respiratory, and cardiovascular phenotypes, some of which provide adaptive advantages to hypoxic conditions compared to populations with sea-level ancestry. Studies performed in populations with a history of high-altitude residence, such as Tibetans, support the idea that many of these phenotypes may be shaped by genomic features that have been positively selected for throughout generations. We hypothesize that such traits observed in Tibetans at high altitude also occur in Tibetans living at intermediate altitude, even in the absence of severe sustained hypoxia. Methodology: We studied individuals of high-altitude ancestry (Tibetans, n = 17 females; n = 12 males) and sea-level ancestry (Han Chinese, n = 6 females; n = 10 males), both who had been living at ∼1300 m (∼4327 ft) for at least 18 months. We measured hemoglobin concentration ([Hb]), hypoxic ventilatory response (HVR), and hypoxic heart rate response (HHRR) with end-tidal CO2 (PetCO2) held constant (isocapnia) or allowed to decrease with hypoxic hyperventilation (poikilocapnia). We also quantified the contribution of CO2 on ventilation and heart rate by calculating the differences of isocapnic versus poikilocapnic hypoxic conditions (Δ V˙I/ΔPetCO2 and ΔHR/ΔPetCO2, respectively). Results: Male Tibetans had lower [Hb] compared to Han Chinese males (p < 0.05), consistent with reports for individuals from these populations living at high altitude and sea level. Measurements of ventilation (resting ventilation, HVR, and PetCO2) were similar for both groups. Heart rate responses to hypoxia were similar in both groups during isocapnia; however, HHRR in poikilocapnia was reduced in the Tibetan group (p < 0.03), and the heart rate response to CO2 in hypoxia was lower in Tibetans relative to Han Chinese (p < 0.01). Conclusion: These results suggest that Tibetans living at intermediate altitude have blunted cardiac responses in the context of hypoxia. Hence, only some of the phenotypes observed in Tibetans living at high altitude are observed in Tibetans living at intermediate altitude. Whereas blunted cardiac responses to hypoxia is revealed at intermediate altitudes, manifestation of other physiological adaptations to high altitude may require exposure to more severe levels of hypoxia.

Clinical, Demographic, and Angiographic Profiles of Amarnath Pilgrims Presenting With Acute Coronary Syndrome.

INTRODUCTION: The challenges posed by high altitude are particularly significant in terms of cardiovascular health. There are currently no data available on acute coronary syndrome (ACS) among Amarnath pilgrims. The objective of this study was to investigate the clinical and angiographic profiles of ACS among Amarnath pilgrims, focusing on demographic characteristics, risk factors, types of ACS, clinical presentation, angiographic findings, and in-hospital outcomes. By examining these aspects, we aimed to provide insights into the unique challenges faced by pilgrims during their spiritual journey and to identify potential strategies for improving the prevention and management of ACS in this population.  Methods: This was a hospital-based, prospective, observational study that included patients who had participated in the pilgrimage and presented with ACS between 2022 and 2023.  Results: Sixty patients were recruited for the study, with a mean age of 51.19 ± 11.17 years. Of these, 43 (71.7%) were male. Risk factors identified in the study included hypertension in 35 (58.3%), smoking in 23 (38.3%), diabetes mellitus in 18 (30%), and dyslipidemia in 25 (41.6%) patients. ST-elevation myocardial infarction (STEMI) was present in 46 (76.66%) patients, Anterior wall myocardial infarction (AWMI) occurred in 29 (48.3%), inferior wall myocardial infarction (IWMI) in 15 (25%), and high lateral wall myocardial infarction (HLWMI) in two (3.3%) patients. Of the 60 patients, 19 (31.6%) were in Killip class I, 16 (26.6%) were in class II, and 25 (41.6%) were in classes III or IV. The average time from the onset of symptoms to hospitalization was 7.6 ± 3.1 hours, significantly higher in those with Killip class III or IV (9.3 ± 3.6 vs. 5.4 ± 2.7 hours, p = 0.01). There were nine (15%) in-hospital deaths, and in the multivariate analysis, advanced Killip class (p = 0.04) and delays in hospitalization of more than six hours (p = 0.03) were found to be significant predictors of mortality. CONCLUSION: In conclusion, 40% of patients presented in the advanced Killip class, and 15% experienced in-hospital mortality. The average time from the onset of symptoms to hospitalization was significantly higher for those categorized in the advanced Killip classes. Our study highlights a significant association between advanced Killip class, delay in hospitalization, and in-hospital mortality among Amarnath pilgrims with ACS, underscoring the importance of timely intervention. It is recommended that appropriate measures be taken to improve patient outcomes in these cases.

High-altitude-induced alterations in intestinal microbiota.

In high-altitude environments characterized by low pressure and oxygen levels, the intestinal microbiota undergoes significant alterations. Whether individuals are subjected to prolonged exposure or acute altitude changes, these conditions lead to shifts in both the diversity and abundance of intestinal microbiota and changes in their composition. While these alterations represent adaptations to high-altitude conditions, they may also pose health risks through certain mechanisms. Changes in the intestinal microbiota induced by high altitudes can compromise the integrity of the intestinal mucosal barrier, resulting in gastrointestinal dysfunction and an increased susceptibility to acute mountain sickness (AMS). Moreover, alterations in the intestinal microbiota have been implicated in the induction or exacerbation of chronic heart failure. Targeted modulation of the intestinal microbiota holds promise in mitigating high-altitude-related cardiac damage. Dietary interventions, such as adopting a high-carbohydrate, high-fiber, low-protein, and low-fat diet, can help regulate the effects of intestinal microbiota and their metabolic byproducts on intestinal health. Additionally, supplementation with probiotics, either through dietary sources or medications, offers a means of modulating the composition of the intestinal microbiota. These interventions may offer beneficial effects in preventing and alleviating AMS following acute exposure to high altitudes.

The involvement of oxidative stress and the TLR4/NF-κB/NLRP3 pathway in acute lung injury induced by high-altitude hypoxia.

OBJECTIVE: This study investigated the effect of oxidative stress and the TLR4/NF-κB/NLRP3 pathway on the pathogenesis of acute lung injury (ALI) induced by high-altitude hypoxia. METHODS: Rats were placed in an animal hyperbaric oxygen chamber to establish a rat model of ALI induced by high-altitude hypoxia after treatment with N-acetylcysteine (NAC; a reactive oxygen species [ROS] inhibitor) or/and MCC950 (an NLPR3 inflammasome inhibitor). After modeling, the wet-to-dry weight ratio (W/D) of rat lung tissues was calculated. In lung tissues, ROS levels were detected with immunofluorescence, the enzyme activity was tested with the kit, and the expression of TLR4/NF-κB/NLRP3 pathway-related genes and proteins was measured with western blotting and qRT-PCR. The levels of inflammatory factors in the serum were quantified with ELISA. RESULTS: After modeling, rats showed significantly increased W/D, ROS levels, and Malondialdehyde (MDA) concentrations and markedly diminished Superoxide dismutase (SOD) and Glutathione (GSH) concentrations in lung tissues (all P < 0.01), accompanied by substantially enhanced serum levels of TNF-α, IL-6, and IL-1ß, significantly reduced serum levels of IL-10, and remarkably augmented TLR4, NLRP3, p-NF-κB p65, NF-κB p65 mRNA, and Caspase-1 expression in lung tissues (all P < 0.01). Furthermore, treatment with NAC or MCC950 alone or in combination prominently lowered the W/D of lung tissues (P < 0.01), serum levels of TNF-α (P < 0.05), IL-6 (P < 0.05), and IL-1ß (P < 0.01), and NF-κB p65 expression and phosphorylation (P < 0.05, P < 0.01) while significantly increasing SOD and GSH concentrations (P < 0.05, P < 0.01) and serum levels of IL-10 (P < 0.01) in modeled rats. Meanwhile, treatment of NAC alone or combined with MCC950 significantly reduced MDA concentration and ROS levels (P < 0.05, P < 0.01) in modeled rats, and treatment of MCC950 alone or combined with NAC considerably declined TLR4, NLRP3, and Caspase-1 expression in modeled rats (P < 0.05, P < 0.01). CONCLUSION: Inhibition of oxidative stress and the TLR4/NF-κB/NLRP3 pathway can ameliorate ALI in rats exposed to high-altitude hypoxia.

Arbuscular Mycorrhizal Fungi Diversity in Sophora japonica Rhizosphere at Different Altitudes and Lithologies.

Arbuscular mycorrhizal fungi play a key role in mediating soil-plant relationships within karst ecosystems. Sophora japonica, a medicinal plant with anti-inflammatory and antitumor properties, is widely cultivated in karst areas of Guangxi, China. We considered limestone, dolomite, and sandstone at altitudes ranging from 100 to 800 m and employed Illumina sequencing to evaluate AMF diversity and identify the factors driving S. japonica rhizosphere AMF community changes. We showed that the increase in altitude increased S. japonica AMF colonization and the Shannon index. The colonization of limestone plots was higher than that of other lithology. In total, 3,096,236 sequences and 5767 OTUs were identified in S. japonica rhizosphere soil. Among these, 270 OTUs were defined at the genus level and divided into 7 genera and 35 species. Moreover, available nitrogen, soil organic matter, and available calcium content had a coupling effect and positive influence on AMF colonization and Shannon and Chao1 indices. Conversely, available phosphorus, available potassium, and available magnesium negatively affected AMF Shannon and Chao1 indices. Lithology, altitude, pH, and available phosphorus are important factors that affect the dynamics of AMF in the S. japonica rhizosphere.

Metabolomic Profiling of Floccularia luteovirens from Different Geographical Regions Proposes a Novel Perspective on Their Antioxidative Activities.

Floccularia luteovirens, an endemic resource of the Tibetan Plateau, possesses significant medicinal and ecological values. However, the understanding of antioxidant capacity and metabolic profiling of F. luteovirens from diverse regions remains elusive due to limited resources. Therefore, to comprehensively comprehend the antioxidant capacity and metabolite diversity of F. luteovirens, we conducted a rounded analysis of its antioxidant capacity from three distinct regions using both untargeted and targeted metabolomics. Determination of antioxidant indices, such as ferric ion-reducing antioxidant power (FRAP), total phenolic content (TPC), and flavonoid content (FC), revealed the robust antioxidant capacity of F. luteovirens. QL F. luteovirens (QLFL) exhibited no significant difference compared to ZD F. luteovirens (ZDFL); however, both were significantly distinct from XH F. luteovirens (XHFL) across multiple indices. Furthermore, a positive correlation was observed between FRAP and flavonoid content. A total of 5782 metabolites were identified and chemically classified. Metabolites of F. luteovirens varied significantly at different regions and eight key differential metabolites were screened. Phenylalanine, tyrosine and tryptophan biosynthesis, phenylalanine metabolism, and cyanoamino acid metabolism were the main different regulatory pathways. Consequently, the disparities in the antioxidant activity of F. luteovirens may primarily be ascribed to the biosynthesis and metabolism of phenylalanine, while vanillic acid could potentially serve as a pivotal metabolite influencing the antioxidative capacity of F. luteovirens by targeted metabolomics. These findings enhance our understanding of the composition of F. luteovirens and provide valuable resources for its comprehensive utilization and targeted development.

Polymorphic transposable elements provide new insights on high-altitude adaptation in the Tibetan Plateau.

Several studies demonstrated that populations living in the Tibetan plateau are genetically and physiologically adapted to high-altitude conditions, showing genomic signatures ascribable to the action of natural selection. However, so far most of them relied solely on inferences drawn from the analysis of coding variants and point mutations. To fill this gap, we focused on the possible role of polymorphic transposable elements in influencing the adaptation of Tibetan and Sherpa highlanders. To do so, we compared high-altitude and middle/low-lander individuals of East Asian ancestry by performing in silico analyses and differentiation tests on 118 modern and ancient samples. We detected several transposable elements associated with high altitude, which map genes involved in cardiovascular, hematological, chem-dependent and respiratory conditions, suggesting that metabolic and signaling pathways taking part in these functions are disproportionately impacted by the effect of environmental stressors in high-altitude individuals. To our knowledge, our study is the first hinting to a possible role of transposable elements in the adaptation of Tibetan and Sherpa highlanders.

Extreme elevational migration spurred cryptic speciation in giant hummingbirds.

The ecoevolutionary drivers of species niche expansion or contraction are critical for biodiversity but challenging to infer. Niche expansion may be promoted by local adaptation or constrained by physiological performance trade-offs. For birds, evolutionary shifts in migratory behavior permit the broadening of the climatic niche by expansion into varied, seasonal environments. Broader niches can be short-lived if diversifying selection and geography promote speciation and niche subdivision across climatic gradients. To illuminate niche breadth dynamics, we can ask how "outlier" species defy constraints. Of the 363 hummingbird species, the giant hummingbird (Patagona gigas) has the broadest climatic niche by a large margin. To test the roles of migratory behavior, performance trade-offs, and genetic structure in maintaining its exceptional niche breadth, we studied its movements, respiratory traits, and population genomics. Satellite and light-level geolocator tracks revealed an >8,300-km loop migration over the Central Andean Plateau. This migration included a 3-wk, ~4,100-m ascent punctuated by upward bursts and pauses, resembling the acclimatization routines of human mountain climbers, and accompanied by surging blood-hemoglobin concentrations. Extreme migration was accompanied by deep genomic divergence from high-elevation resident populations, with decisive postzygotic barriers to gene flow. The two forms occur side-by-side but differ almost imperceptibly in size, plumage, and respiratory traits. The high-elevation resident taxon is the world's largest hummingbird, a previously undiscovered species that we describe and name here. The giant hummingbirds demonstrate evolutionary limits on niche breadth: when the ancestral niche expanded due to evolution (or loss) of an extreme migratory behavior, speciation followed.

PaCO2 Association with Outcomes of Patients with Traumatic Brain Injury at High Altitude: A Prospective Single-Center Cohort Study.

BACKGROUND: Partial pressure of carbon dioxide (PaCO2) is generally known to influence outcome in patients with traumatic brain injury (TBI) at normal altitudes. Less is known about specific relationships of PaCO2 levels and clinical outcomes at high altitudes. METHODS: This is a prospective single-center cohort of consecutive patients with TBI admitted to a trauma center located at 2600 m above sea level. An unfavorable outcome was defined as a Glasgow Outcome Scale-Extended (GOSE) score < 4 at the 6-month follow-up. RESULTS: We had a total of 81 patients with complete data, 80% (65/81) were men, and the median (interquartile range) age was 36 (25-50) years. Median Glasgow Coma Scale (GCS) score on admission was 9 (6-14); 49% (40/81) of patients had severe TBI (GCS 3-8), 32% (26/81) had moderate TBI (GCS 12-9), and 18% (15/81) had mild TBI (GCS 13-15). The median (interquartile range) Abbreviated Injury Score of the head (AISh) was 3 (2-4). The frequency of an unfavorable outcome (GOSE < 4) was 30% (25/81), the median GOSE was 4 (2-5), and the median 6-month mortality rate was 24% (20/81). Comparison between patients with favorable and unfavorable outcomes revealed that those with unfavorable outcome were older, (median age 49 [30-72] vs. 29 [22-41] years, P < 0.01), had lower admission GCS scores (6 [4-8] vs. 13 [8-15], P < 0.01), had higher AISh scores (4 [4-4] vs. 3 [2-4], P < 0.01), had higher Acute Physiology and Chronic Health disease Classification System II scores (17 [15-23] vs. 10 [6-14], P < 0.01), had higher Charlson scores (0 [0-2] vs. 0 [0-0], P < 0.01), and had higher PaCO2 levels (mean 35 ± 8 vs. 32 ± 6 mm Hg, P < 0.01). In a multivariate analysis, age (odds ratio [OR] 1.14, 95% confidence interval [CI] 1.1-1.30, P < 0.01), AISh (OR 4.7, 95% CI 1.55-21.0, P < 0.05), and PaCO2 levels (OR 1.23, 95% CI 1.10-1.53, P < 0.05) were significantly associated with the unfavorable outcomes. When applying the same analysis to the subgroup on mechanical ventilation, AISh (OR 5.4, 95% CI 1.61-28.5, P = 0.017) and PaCO2 levels (OR 1.36, 95% CI 1.13-1.78, P = 0.015) remained significantly associated with the unfavorable outcome. CONCLUSIONS: Higher PaCO2 levels are associated with an unfavorable outcome in ventilated patients with TBI. These results underscore the importance of PaCO2 levels in patients with TBI and whether it should be adjusted for populations living at higher altitudes.

The cardiovascular system at high altitude: A bibliometric and visualization analysis.

BACKGROUND: When exposed to high-altitude environments, the cardiovascular system undergoes various changes, the performance and mechanisms of which remain controversial. AIM: To summarize the latest research advancements and hot research points in the cardiovascular system at high altitude by conducting a bibliometric and visualization analysis. METHODS: The literature was systematically retrieved and filtered using the Web of Science Core Collection of Science Citation Index Expanded. A visualization analysis of the identified publications was conducted employing CiteSpace and VOSviewer. RESULTS: A total of 1674 publications were included in the study, with an observed annual increase in the number of publications spanning from 1990 to 2022. The United States of America emerged as the predominant contributor, while Universidad Peruana Cayetano Heredia stood out as the institution with the highest publication output. Notably, Jean-Paul Richalet demonstrated the highest productivity among researchers focusing on the cardiovascular system at high altitude. Furthermore, Peter Bärtsch emerged as the author with the highest number of cited articles. Keyword analysis identified hypoxia, exercise, acclimatization, acute and chronic mountain sickness, pulmonary hypertension, metabolism, and echocardiography as the primary research hot research points and emerging directions in the study of the cardiovascular system at high altitude. CONCLUSION: Over the past 32 years, research on the cardiovascular system in high-altitude regions has been steadily increasing. Future research in this field may focus on areas such as hypoxia adaptation, metabolism, and cardiopulmonary exercise. Strengthening interdisciplinary and multi-team collaborations will facilitate further exploration of the pathophysiological mechanisms underlying cardiovascular changes in high-altitude environments and provide a theoretical basis for standardized disease diagnosis and treatment.

Assessment of Dynamic Cerebral Autoregulation During Long-Term Exposure to High Altitude in Normal Subjects by Ultrasonography.

PURPOSE: To evaluate changes in dynamic cerebral autoregulation (CA) during short-term and long-term exposure to high altitude with ultrasonography, and also study the sex differences in the response of CA to altitude. METHODS: We assessed the differences in dynamic CA and measured with Doppler ultrasound of the bilateral internal carotid artery (ICA), vertebral artery (VA), and middle cerebral artery (MCA) and the values of basic information within 48 hours and at 2 years after arrival at Tibet in 65 healthy Han young Chinese volunteers, meanwhile, we compared the resistance index (RI) and pulsatility index (PI) of the right MCA at inhale oxygen 8 minutes when a newcomer with 2 years after arrival at Tibet. RESULTS: With 2 years of altitude exposure, the SaO2 of all subjects was above 90%, the mean PEF, DAP, and HR values decreased, HGB increased compared within 48 hours in same-gender groups. Comparisons of cerebral hemodynamics between before 2 years and after 2 years within male and female groups, the mean RI and PI values of bilateral MCA after 2 years were significantly higher than before 2 years, at the same time, the mean RI and PI values of bilateral ICA were significant differences (P < .05) between male groups, with regard to female groups, showed that the mean RI and PI values of bilateral VA were significant differences (P < .05). Comparisons of Right MCA hemodynamics between after oxygen uptake 8 minutes and 2 years, the mean RI and PI values were no significant difference within male and female groups (P > .05). CONCLUSIONS: Acute mountain sickness could result from an alteration of dynamic autoregulation of cerebral blood flow, but the impaired autoregulation may be corrected with the extension of time, furthermore, the response of CA to altitude in males and females are different.

Pain control and neonatal outcomes in 211 women under epidural anesthesia during childbirth at high altitude in Qinghai, China.

Background: High altitudes are characterized by low-pressure oxygen deprivation. This is further exacerbated with increasing altitude. High altitudes can be associated with reduced oxygenation, which in turn, can affect labor, as well as maternal and fetal outcomes. Epidural anesthesia can significantly relieve labor pain. This study aimed to assess the effects of elevation gradient changes at high altitude on the analgesic effect of epidural anesthesia, labor duration, and neonatal outcomes. Methods: We divided 211 women who received epidural anesthesia into groups according to varying elevation of their residence (76 in Xining City, mean altitude 2,200 m; 63 in Haibei Prefecture, mean altitude 3,655 m; and 72 in Yushu Prefecture, mean altitude 4,493 m). The analgesic effect was assessed using a visual analog scale (VAS). Labor duration was objectively recorded. The neonatal outcome was assessed using Apgar scores and fetal umbilical artery blood pH. Results: VAS scores among the three groups did not differ significantly (p > 0.05). The neonatal Apgar scores in descending order were: Xining group > Haibei group > Yushu group (p < 0.05). The stage of labor was similar among the three groups (p > 0.05). Fetal umbilical artery blood pH in descending order were: Xining group > Haibei group > Yushu group (p < 0.05). Conclusion: Elevation gradient changes in highland areas did not affect the efficacy of epidural anesthesia or labor duration. However, neonatal outcomes were affected.

Association between sugar-sweetened beverages and duration of physical exercise with psychological symptoms among Tibetan university students at high altitude.

Background: Sugar-sweetened beverages (SSBs) and duration of physical exercise are strongly associated with physical health. Unfortunately, there are few studies focused on the association with psychological symptoms, let alone Tibetan university students at high altitudes in China. Methods: A stratified cluster sampling method was used to include 8,268 Tibetan university students aged 19-22 years in Qinghai and Tibet, both of which are high-altitude regions of China. Self-assessment questionnaires on SSBs, duration of physical exercise, and psychological symptoms were administered. The chi-square test and logistic regression analysis were used to analyze the associations among them. Results: The detection rate of psychological symptoms among Tibetan university students in high-altitude areas of China was 16.7%, with in girls (18.2%) higher than that in boys (14.8%), and the difference was statistically significant (χ2 = 11.73, p < 0.01). The proportion of SSBs for university students ≤1 time/week, 2-5 times/week, and ≥ 6 times/week were 54.2, 24.3, and 21.5%, respectively. The proportion of duration of physical exercise for >60 min/d was only 5.4%. Logistic regression analysis showed that compared with the SSBs ≤1 time/week group of university students, SSBs 2-5 times/week (OR = 1.45, 95% CI: 1.24-1.70) and ≥ 6 times/week (OR = 3.06, 95% CI: 2.62-3.57) had an increased risk of psychological symptoms (p < 0.001). In the reference group, the risk of psychological symptoms was also significantly increased in the group of university students with duration of physical exercise >60 min/d (OR = 2.08, 95% CI: 1.48-2.93), and the risk of psychological symptoms was also significantly increased in the group with duration of physical exercise <30 min/d (OR = 2.08, 95% CI: 1.48-2.93). The risk of psychological symptoms was also significantly increased in the university students with the duration of physical exercise <30 min/d (OR = 2.08, 95% CI: 1.48 ~ 2.93) group. Conclusion: SSBs and exercise time may be important influences on the psychological symptoms of Tibetan university students at high altitudes in China. This study has important implications for mental health planning in universities in highland areas and may also provide guidance for mental health interventions for Tibetan university students.

Inappropriate Acetazolamide Use for a Hiker Who Developed Acute Kidney Injury.

Prophylactic use of acetazolamide (ACZ) to prevent acute mountain sickness (AMS) is a common practice among high altitude travelers and mountaineers. With its use comes a possible risk of acute kidney injury (AKI). We present a case in which a 56-year-old male hiker in Grand Canyon National Park developed acute exertional rhabdomyolysis and subsequent AKI while taking prophylactic ACZ to prevent AMS. This medication was prescribed despite the hiker encountering only moderate altitude at Grand Canyon with a planned descent within <24 h. The resulting AKI was determined to be the combined result of acute exertional rhabdomyolysis and dehydration/hypovolemia, with the ACZ, a diuretic, as a contributing factor. Medical providers need to recognize the risks/benefits with ACZ use for AMS prophylaxis and avoid prescribing it to individuals whose altitude exposure and activity fall outside the clinical practice guidelines recommended for use.