Clinical and biochemical indices of people with high-altitude experience linked to acute mountain sickness

Liu, Bao; Xu, Gang; Sun, Bing‐Da; Wu, Gang; Chen, Jian; Gao, Yuqi

doi:10.1016/j.tmaid.2022.102506

Cited by 9 publications

(4 citation statements)

References 33 publications

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“…Another distinctive feature of hypoxic exposure is the activation of the immune-inflammatory responses, in which PDGF-AB is involved. We found that 6 h of hypoxia caused a significant neutrophil-dependent inflammatory response, which was consistent with previous studies [ 38 , 39 ]. Particularly, our results showed that PDGF-AB, a downstream product of hypoxia-inducible factor (HIF) pathway, played a role during acute hypoxic exposure.…”

Section: Discussionsupporting

confidence: 93%

Effects of acetazolamide combined with remote ischemic preconditioning on risk of acute mountain sickness: a randomized clinical trial

Liu,

Jiao,

et al. 2024

BMC Med

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Background We aimed to determine whether and how the combination of acetazolamide and remote ischemic preconditioning (RIPC) reduced the incidence and severity of acute mountain sickness (AMS). Methods This is a prospective, randomized, open-label, blinded endpoint (PROBE) study involving 250 healthy volunteers. Participants were randomized (1:1:1:1:1) to following five groups: Ripc (RIPC twice daily, 6 days), Rapid-Ripc (RIPC four times daily, 3 days), Acetazolamide (twice daily, 2 days), Combined (Acetazolamide plus Rapid-Ripc), and Control group. After interventions, participants entered a normobaric hypoxic chamber (equivalent to 4000 m) and stayed for 6 h. The primary outcomes included the incidence and severity of AMS, and SpO2 after hypoxic exposure. Secondary outcomes included systolic and diastolic blood pressure, and heart rate after hypoxic exposure. The mechanisms of the combined regime were investigated through exploratory outcomes, including analysis of venous blood gas, complete blood count, human cytokine antibody array, ELISA validation for PDGF-AB, and detection of PDGF gene polymorphisms. Results The combination of acetazolamide and RIPC exhibited powerful efficacy in preventing AMS, reducing the incidence of AMS from 26.0 to 6.0% (Combined vs Control: RR 0.23, 95% CI 0.07–0.70, P = 0.006), without significantly increasing the incidence of adverse reactions. Combined group also showed the lowest AMS score (0.92 ± 1.10). Mechanistically, acetazolamide induced a mild metabolic acidosis (pH 7.30 ~ 7.31; HCO3− 18.1 ~ 20.8 mmol/L) and improved SpO2 (89 ~ 91%) following hypoxic exposure. Additionally, thirty differentially expressed proteins (DEPs) related to immune-inflammatory process were identified after hypoxia, among which PDGF-AB was involved. Further validation of PDGF-AB in all individuals showed that both acetazolamide and RIPC downregulated PDGF-AB before hypoxic exposure, suggesting a possible protective mechanism. Furthermore, genetic analyses demonstrated that individuals carrying the PDGFA rs2070958 C allele, rs9690350 G allele, or rs1800814 G allele did not display a decrease in PDGF-AB levels after interventions, and were associated with a higher risk of AMS. Conclusions The combination of acetazolamide and RIPC exerts a powerful anti-hypoxic effect and represents an innovative and promising strategy for rapid ascent to high altitudes. Acetazolamide improves oxygen saturation. RIPC further aids acetazolamide, which synergistically regulates PDGF-AB, potentially involved in the pathogenesis of AMS. Trial registration ClinicalTrials.gov NCT05023941.

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Section: Discussionsupporting

confidence: 93%

Effects of acetazolamide combined with remote ischemic preconditioning on risk of acute mountain sickness: a randomized clinical trial

Liu,

Jiao,

et al. 2024

BMC Med

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“…11C). Differential PM expression levels may account for altitude sickness severity when rapidly ascending to high altitudes, consistent with a previous study [47].…”

Section: Discussionsupporting

confidence: 91%

“…Hypoxia stimulates glycolysis while disrupting the glycolytic pathway, purine degradation, and glutathione homeostasis [5]. Previous research reported that changes in uric acid concentrations before and during highaltitude exposure could be used to identify AMS [47]. From our analyses of PM pathway characteristics, differences between males and females were distinct at T1 (Fig.…”

Section: Discussionmentioning

confidence: 74%

Serum metabolite changes are implicated in high-altitude acclimatization and de-acclimatization

Wei,

Liu,

Yang

et al. 2024

Preprint

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For individuals from lowland areas traveling to high-altitude regions, acclimatization and de-acclimatization (ADA) to high altitudes is an inevitable physiological process, accompanied by complex metabolic adjustments. In this study, we investigated 18 subjects (nine males and nine females) who traveled to and remained at an altitude of 4200 m for 3 months. We used untargeted metabolomics to analyze serum metabolomic changes after this period and then at specific time points after their return to the plains. We observed considerable differential serum metabolite expression at T1 (after the 3 month-high-altitude stay), T2 (day 2 after returning to the plains), and T3 (day 30 after returning to the plains). Gender differences and initial high-altitude response levels also affected metabolite changes. Metabolite-related signaling pathway analyses showed that the most significant differential metabolic pathways at T1 and T2 were pentose phosphate pathway (PPP), butanoate metabolism, arginine biosynthesis, and glucagon signaling pathways. The most significant differential metabolic pathways at T1 and T3 were galactose metabolism, arginine biosynthesis, sphingolipid signaling pathway, ATP-binding cassette (ABC) transporter, and biosynthesis of unsaturated fatty acid (FA) pathways. The most significant differential metabolic pathways between males and females at T1 were ABC transporter, purine metabolism (PM), central carbon metabolism in cancer (CCMiC), ascorbate and aldarate metabolism (AAM), and valine, leucine, and isoleucine biosynthesis pathways. Thus, during ADA to high altitudes, ABC transporter, PP, pentose and glucuronate interconversion (PGI), and PM signaling pathways had important roles. Our data provide new insights into the metabolic changes during ADA to high altitudes.

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“…In this study, we found people from lower altitude of resident place had the higher proportions of AMS occurence, which indicated migrants from lower altitude areas were much more prone to AMS, mainly owing to unacclimatization to the hypobaric hypoxic environment of high altitudes 1,15 . Moreover, air travel has become the preferred way of transportation for most tourists, but a large observational study found that when tourists rapidly ascended to high-altitude destinations by air, the incidence of AMS increased by 4.5 times; in contrast, the incidence increased only by 2.1% for those who travelled by foot or a combination of walking, driving and flying 2 .…”

Section: (Which Was Not Certified By Peer Review)mentioning

confidence: 57%

Association of demographic factors with acute mountain sickness: a retrospective study in Litang

Zhao,

Wang,

Wang

et al. 2024

Preprint

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ObjectiveAcute mountain sickness (AMS) is a common clinical syndrome in high altitude areas, but the role of demographic factors in AMS has not been well-illucidated. This study aims to describe the relationship between demographic factors and AMS in Litang, one of the highest-altitude town in the world.MethodsDemographic data of patients diagnosed with AMS from January 2022 to December 2023 were collected from the information management system of Litang County People’s Hospital, including gender, age, onset time, ethnicity, current residence and its altitude. Descriptive statistical methods were used to describe these factors.Results7,290 AMS patients were included, among which 62.37% (4,547/7,290) were male and 37.63% (2,743/7,290) were female; 90.41% (6,591/7,290) were non-Tibetan, and 9.59% (699/7,290) were Tibetan; the age group 20-29 had the highest number of patients (2,422, 39.08%), and the incidence of AMS generally decreased with age; the proportion of AMS occurring from May to August reached 51.99% (3,790/7,290); the percentage from lower altitude areas was 79.05% (4,333/7,150).ConclusionsThese data from Litang suggest higher incidence of AMS may be detected in males, non-Tibetans, young people, summer time and residents from lower altitude. Special attention should be paid to these demographic factors for preventing the occurrence of AMS.

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Clinical and biochemical indices of people with high-altitude experience linked to acute mountain sickness

Cited by 9 publications

References 33 publications

Effects of acetazolamide combined with remote ischemic preconditioning on risk of acute mountain sickness: a randomized clinical trial

Effects of acetazolamide combined with remote ischemic preconditioning on risk of acute mountain sickness: a randomized clinical trial

Serum metabolite changes are implicated in high-altitude acclimatization and de-acclimatization

Association of demographic factors with acute mountain sickness: a retrospective study in Litang

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