Lake Louise Score Research Articles

Temporal changes in biomarkers in individuals with and without acute mountain sickness following rapid ascent

BackgroundField studies have reported conflicting results regarding changes in biomarkers at high altitude. This study measured temporal changes in biomarkers and compared the differences between individuals with and without acute mountain sickness (AMS). Materials and methodsThis study included 34 nonacclimatized healthy participants. Ten-milliliters of blood were collected at four time points: 3 days before ascent (T0), on two successive nights at 3150 m (T1 and T2), and 2 days after descent (T3). Participants were transported by bus from 555 m to 3150 m within 3 hours. AMS was diagnosed using the self-reported Lake Louise Scoring (LLS) questionnaire. ResultsCompared with T0, significant increases in E-selectin and decreases in vascular endothelial growth factor (VEGF) levels were observed at high altitude. Significantly increased C-reactive protein (CRP), monocyte chemoattractant protein-1 (MCP-1), and S100 calcium-binding protein B (S100B) levels were observed at T2, and significantly decreased vascular cell adhesion molecule-1 (VCAM-1) levels were observed at T3. Eighteen (53%) participants developed AMS. Changes in E-selectin, CRP, MCP-1, and S100B levels were independent of AMS. Relative to individuals without AMS, those with AMS had significantly higher atrial natriuretic peptide (ANP) and VCAM-1 levels and lower plasminogen activator inhibitor-1 (PAI-1) levels at T1 and higher brain natriuretic peptide and lower VEGF and PAI-1 levels at T3. LLSs were positively correlated with ANP and VCAM-1 levels and negatively correlated with PAI-1 levels measured at T1. ConclusionsAfter acute ascent, individuals with and without AMS exhibited different trends in biomarkers associated with endothelial cell activation and natriuretic peptides.

High Altitude Illness among Rapidly Ascending Pilgrims to Kailash Mansarovar.

High altitude pilgrims typically ascend rapidly, are not well prepared for the austere environment and tend to have multiple co-morbidities. Here, we list the trend of altitude and other illnesses who visited Humla district hospital (2,950 meters) following very rapid ascent to Kailash Mansarovar (4,500 meters). A prospective study was conducted among 55 patients at the Humla District Hospital from September 2019 - August 2022. Patients who fell ill during pilgrimage and brought to the hospital were included. The patients were assessed with medical history and clinical examination. Lake Louise Score Acute Mountain Sickness Score (2018) was used for the diagnosis of Acute Mountain Sickness. A total of 56 evacuees visited the hospital which included 55 patients and 1 brought dead. The mean age was 50.63 ±10.91 years. Sixteen patients (29.1%) developed symptoms within 24 hours and 15 patients (27.3%) within 48 hours of ascent. Headache 42 (76.4%) was the most common complain. Mild acute mountain sickness (30.9%; 17 patients) was the most common altitude related illness while 14 patients (25.4%) were diagnosed with non-altitude related illnesses. Twelve patients (21.8%) had co-morbidities like hypertension and diabetes mellitus. In the rapidly ascending pilgrims, majority of travelers requiring medical attention are suffering from some form of altitude illnesses. Hence, proper planning and public awareness about slow and gradual ascent profile is necessary to make the travel safer.

AZU1 (HBP/CAP37) and PRKCG (PKC-gamma) may be candidate genes affecting the severity of acute mountain sickness

BackgroundAcute Mountain Sickness (AMS) is one of the diseases that predispose to sudden ascent to high altitudes above 2500 m. Among the many studies on the occurrence and development of AMS, there are few studies on the severity of AMS. Some unidentified phenotypes or genes that determine the severity of AMS may be vital to elucidating the mechanisms of AMS. This study aims to explore the underlying genes or phenotypes associated with AMS severity and to provide evidence for a better understanding of the mechanisms of AMS.MethodsGSE103927 dataset was downloaded from the Gene Expression Omnibus database, and a total of 19 subjects were enrolled in the study. Subjects were divided into a moderate to severe AMS (MS-AMS, 9 subjects) group and a no or mild AMS (NM-AMS, 10 subjects) group based on the Lake Louise score (LLS). Various bioinformatics analyses were used to compare the differences between the two groups. Another dataset, Real-time quantitative PCR (RT-qPCR), and another grouping method were used to validate the analysis results.ResultNo statistically significant differences in phenotypic and clinical data existed between the MS-AMS and NM-AMS groups. Eight differential expression genes are associated with LLS, and their biological functions are related regulating of the apoptotic process and programmed cell death. The ROC curves showed that AZU1 and PRKCG had a better predictive performance for MS-AMS. AZU1 and PRKCG were significantly associated with the severity of AMS. The expression of AZU1 and PRKCG were significantly higher in the MS-AMS group compared to the NM-AMS group. The hypoxic environment promotes the expression of AZU1 and PRKCG. The results of these analyses were validated by an alternative grouping method and RT-qPCR results. AZU1 and PRKCG were enriched in the Neutrophil extracellular trap formation pathway, suggesting the importance of this pathway in influencing the severity of AMS.ConclusionAZU1 and PRKCG may be key genes influencing the severity of acute mountain sickness, and can be used as good diagnostic or predictive indicators of the severity of AMS. Our study provides a new perspective to explore the molecular mechanism of AMS.

Effects of age on hypoxic tolerance in women

Effects of age on hypoxic tolerance in women

IoT-Enabled Intelligent Dynamic Risk Assessment of Acute Mountain Sickness: The Role of Event-Triggered Signal Processing

The rapid developments in Internet of Medical Things open up new avenues for personalized healthcare. Continuously monitored physiological data can be collected by wearable devices and are transmitted to a remote server for real-time monitoring and diagnosis. This article concerns a risk assessment problem of acute mountain sickness (AMS) with data transmitted according to an event-triggered transmission schedule. An event-triggered signal processing approach is introduced to reconstruct the untransmitted information, based on which, a dynamic SpO <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"><tex-math notation="LaTeX">$_{\bf 2}$</tex-math></inline-formula> index (DSI) is further proposed for AMS risk evaluation. The performance of the proposed approach is analyzed through physiological data collected in a proof-of-the-concept study ( <italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">N</i> =12). Statistical significant correlation of the DSI with AMS ground truth including Lake Louise score, deep sleep duration, deep sleep ratio, and mean SpO <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"><tex-math notation="LaTeX">$_{\bf 2}$</tex-math></inline-formula> during sleep is observed. More importantly, it is observed that the proposed event-triggered signal processing procedure can dramatically reduce the data transmission rate while maintaining the performance of the DSI assessment, through comparison of the DSI obtained using the proposed event-triggered approach with those obtained based on event-triggered raw data and continuously transmitted time-triggered data. The obtained results indicate the feasibility of adopting event-triggered data scheduling and signal processing to achieve AMS risk evaluation using data from wearable devices with limited communication/battery resources.

Hypoxia-altitude simulation test to predict altitude-related adverse health effects in COPD patients.

Amongst numerous travellers to high altitude (HA) are many with the highly prevalent COPD, who are at particular risk for altitude-related adverse health effects (ARAHE). We then investigated the hypoxia-altitude simulation test (HAST) to predict ARAHE in COPD patients travelling to altitude. This prospective diagnostic accuracy study included 75 COPD patients: 40 women, age 58±9 years, forced expiratory volume in 1 s (FEV1) 40-80% pred, oxygen saturation measured by pulse oximetry (S pO2 ) ≥92% and arterial carbon dioxide tension (P aCO2 ) <6 kPa. Patients underwent baseline evaluation and HAST, breathing normobaric hypoxic air (inspiratory oxygen fraction (F IO2 ) of 15%) for 15 min, at low altitude (760 m). Cut-off values for a positive HAST were set according to British Thoracic Society (BTS) guidelines (arterial oxygen tension (P aO2 ) <6.6 kPa and/or S pO2 <85%). The following day, patients travelled to HA (3100 m) for two overnight stays where ARAHE development including acute mountain sickness (AMS), Lake Louise Score ≥4 and/or AMS score ≥0.7, severe hypoxaemia (S pO2 <80% for >30 min or 75% for >15 min) or intercurrent illness was observed. ARAHE occurred in 50 (66%) patients and 23 out of 75 (31%) were positive on HAST according to S pO2 , and 11 out of 64 (17%) according to P aO2 . For S pO2 /P aO2 we report a sensitivity of 46/25%, specificity of 84/95%, positive predictive value of 85/92% and negative predictive value of 44/37%. In COPD patients ascending to HA, ARAHE are common. Despite an acceptable positive predictive value of the HAST to predict ARAHE, its clinical use is limited by its insufficient sensitivity and overall accuracy. Counselling COPD patients before altitude travel remains challenging and best focuses on early recognition and treatment of ARAHE with oxygen and descent.

Intraocular pressure changes at high altitude

AbstractPurpose: The effect of altitude on Intraocular Pressure has been debated for decades. The literature is unclear, encompassing exertional and non‐exertional ascents, as well as simulated ascents, with most finding a decrease in IOP, but some finding no change or an increase. Additionally, several papers have previously corrected IOP for Central Corneal Thickness, further confounding efforts to draw conclusions from the literature. The Imperial Remote Medicine BSc's Morocco expedition aimed to assess changes in IOP and CCT during an exertional winter ascent of Mount Toubkal (4167 m) which to our knowledge is the first exertional study conducted partially in sub‐zero temperatures.Methods: IOP, CCT, clinical parameters and Lake Louise Score (LLS) were recorded daily in 9 participants before, 1 month after and during the expedition. Participants flew into Marrakesh, ascended to Imlil (1886 m) by car, and ascended from there on foot, stayed at the Nelter refuge for 3 nights (3037 m). All measurements were taken in the evening. IOP was measured using an iCare ic200 tonometer. Total IOP and CCT per participant per day was used to assess more fully the overall change in IOP and CCT across the expedition. Differences between eyes were also assessed.Results: No significant change in IOP was seen. CCT increased significantly at altitude. IOP was significantly positively correlated with LLS and headache, and significantly negatively correlated with SpO2. In line with current clinical practice, IOP was not adjusted for CCT. There was no difference in IOP or CCT between contact users and non‐contact users.Conclusions: The increase in CCT is in line with the existing literature. The lack of significant change in IOP has precedence, and we propose that it is the interplay of physiological changes at altitude, alongside other factors such as exertion and temperature that alter IOP rather than IOP changes simply being a function of altitude.

Unveiling Interpretable Key Performance Indicators in Hypoxic Response: A System Identification Approach

Advances in wireless networks and wearable electronic devices have enabled the monitoring of massive physiological data for disease diagnosis. In this article, we aim to explore the hypoxic response dynamics through the use of system identification based on physiological data monitored by wearable devices. A third-order autoregressive moving average with exogenous inputs model is developed to describe the dominant system dynamics, based on which an interpretable index called “sum of distance” (SoD) is proposed from a systems and control perspective for AMS risk evaluation. The effectiveness of SoD is evaluated on the basis of physiological data from a proof-of-the-concept study. Statistically, significant relationships of DSI with ground truth AMS metrics (including, Lake Louise score, deep sleep duration, and deep sleep ratio) are observed. To accelerate the evaluation algorithm design, a simulator is designed. A model parameter selection method based on the three-sigma rule is proposed to generate an <italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">in silico</i> population, and a total disturbance sequence is determined for disturbance simulation. The created data has the same trend as the real measurements. The proposed method and experimental results indicate the feasibility of improving the AMS risk evaluation performance by understanding and learning the hypoxic response mechanism.

Optic nerve sheath diameter changes at altitude

AbstractPurpose: This study aimed to assess variations in Optic Nerve Sheath Diameter (ONSD) as a correlate of Intracranial Pressure (ICP) during ascent to high‐altitude and to explore the relationship between ONSD and Acute Mountain Sickness (AMS). AMS is a high‐altitude illness characterized by headaches, lethargy, nausea and vomiting. At present there is no consensus on the pathophysiology of AMS. There are similarities in symptomology between AMS and raised ICP. A greater understanding of ICP at altitude and its role in AMS may yield new strategies for management of the illness.Methods: We conducted a longitudinal cohort study involving 10 mountaineers climbing Mt Toubkal (4167 m). Participants underwent daily binocular ultrasound B‐scans at interval altitudes during the ascent. Altitude, AMS diagnosis and severity (using Lake Louise Score [LLS]) were recorded concurrently with ultrasound examinations. Ultrasound scans were reviewed by a blinded observer who measured ONSD and assessed image quality (1 = poor, 2 = moderate, 3 = good).Results: During the ascent to 4167 m and return to low‐land, there was no significant variation in left (p = 0.97), right (p = 0.68) or mean (p = 0.86) ONSD. The ratio of ONSD to baseline was significantly (p = 0.038) greater in participants with AMS on Day 5; this was not consistent across all time points. No significant correlation between the ratio of ONSD to baseline and LLS was observed at any time point. Mean image quality was 2.12 (SD ± 0.65); images largely scored in the ‘Moderate’ – ‘Good’ range.Conclusions: This study is reflective of changes in ONSD during slow ascent profiles commonly used in mountaineering. This suggests that ONSD and therefore ICP does not significantly vary during this style of ascent to 4167 m. We did not identify any convincing relationship between AMS and ONSD, adding to previous research suggesting the same. Considering the limitations of this study, it cannot stand alone to disapprove a causal relationship between ONSD and AMS.

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

BackgroundAcute mountain sickness (AMS) is a major health issue for people travelling to high altitudes. This study was designed to comprehensively evaluate the changes in clinical characteristics and biochemical indices of high-altitude travelers and determine whether these changes were associated with AMS. MethodsA total of 14 clinical indices and 52 biochemical indices were determined in 22 subjects before and during acute high-altitude exposure. Six hours after passive ascent to 3648 m (Lhasa, China), the Lake Louise Scoring (LLS) system 2018 was used to assess AMS, which was defined as headache with a total LLS ≥3. ResultsBefore travelling to high altitudes, uric acid (UA), platelet distribution width (PDW), mitral peak E velocity (MVE), and ejection fraction (EF) were significantly higher in AMS-resistant individuals than in AMS-susceptible ones (all p < 0.05). A good predictive value of UA (0.817, 95% CI: 0.607–1.000) and PDW (0.844, 95% CI: 0.646–1.000) for AMS-susceptible subjects was found. With high-altitude experience, 14 subjects were diagnosed as having AMS. Compared with non-AMS, the changes in UA and number of neutrophils in AMS presented a significant difference (all p < 0.05). The high-altitude-induced changes in UA, area under the curve, specificity, and sensitivity for identifying AMS were 0.883 (95% CI: 0.738–1.000), 83.30%, and 90.00%, respectively. ConclusionHuman presents a compensatory physiological and biochemical response to high-altitude travel at early phase. The UA concentration before travel and its trend with high-altitude experience exhibited good performance for identifying AMS.

A slow feature based LSTM network for susceptibility assessment of acute mountain sickness with heterogeneous data

Objective:Acute mountain sickness (AMS) is a syndrome that occurs when an individual rapidly rises to a high altitude and fails to adapt to acute hypobaric hypoxia physiologically. The aim of this paper is to develop an intelligent approach for the individual susceptibility assessment of AMS based on dynamic heterogeneous data monitored by multiple wearable devices. Methods:In this paper, the adaptive domain of hypoxia tolerance (ADHT) is established based on k-means clustering and mutual information (MI). Furthermore, a slow feature based long short-term memory (LSTM) learner is proposed to evaluate an individual’s ability to tolerate hypoxia, which is used as the susceptibility evaluation of AMS. Results:The proposed method’s performance is evaluated by using the heterogeneous physiological data of 18 subjects, augmented to 396 samples. The maximum MI value (0.3946) between cluster results and the lake louise score is retained to establish ADHT. The classification accuracy of the slow feature based LSTM method reaches 85.71% and the area under the ROC curve reaches 0.925. Comparing with other benchmark and deep learning approaches, the proposed method perform best in term of accuracy, precision, specificity and Matthews correlation coefficient. Conclusion:The results show that the proposed method is feasible in classifying individual hypoxia tolerance and evaluating AMS susceptibility. The system takes full advantage of dynamic heterogeneous data during offline modeling, and only needs the IHT data fed back by wearable devices during online monitoring. Significance:The method improves the convenience of susceptibility assessment of AMS.

Effectiveness, implementation, and monitoring variables of intermittent hypoxic bicycle training in patients recovered from COVID-19: The AEROBICOVID study.

Hypoxic exposure is safely associated with exercise for many pathological conditions, providing additional effects on health outcomes. COVID-19 is a new disease, so the physiological repercussions caused by exercise in affected patients and the safety of exposure to hypoxia in these conditions are still unknown. Due to the effects of the disease on the respiratory system and following the sequence of AEROBICOVID research work, this study aimed to evaluate the effectiveness, tolerance and acute safety of 24 bicycle training sessions performed under intermittent hypoxic conditions through analysis of peripheral oxyhemoglobin saturation (SpO2), heart rate (HR), rate of perceived exertion (RPE), blood lactate concentration ([La-]) and symptoms of acute mountain sickness in patients recovered from COVID-19. Participants were allocated to three training groups: the normoxia group (GN) remained in normoxia (inspired fraction of O2 (FiO2) of ∼20.9%, a city with 526m altitude) for the entire session; the recovery hypoxia group (GHR) was exposed to hypoxia (FiO2 ∼13.5%, corresponding to 3,000m altitude) all the time except during the effort; the hypoxia group (GH) trained in hypoxia (FiO2 ∼13.5%) throughout the session. The altitude simulation effectively reduced SpO2 mean with significant differences between groups GN, GHR, and GH, being 96.9(1.6), 95.1(3.1), and 87.7(6.5), respectively. Additionally, the proposed exercise and hypoxic stimulus was well-tolerated, since 93% of participants showed no or moderate acute mountain sickness symptoms; maintained nearly 80% of sets at target heart rate; and most frequently reporting session intensity as an RPE of "3" (moderate). The internal load calculation, analyzed through training impulse (TRIMP), calculated using HR [TRIMPHR = HR * training volume (min)] and RPE [TRIMPRPE = RPE * training volume (min)], showed no significant difference between groups. The current strategy effectively promoted the altitude simulation and monitoring variables, being well-tolerated and safely acute exposure, as the low Lake Louise scores and the stable HR, SpO2, and RPE values showed during the sessions.

Ascent rate and the Lake Louise scoring system: An analysis of one year of emergency ward entries for high-altitude sickness at the Mustang district hospital, Nepal.

More travellers are making swift ascents to higher altitudes without sufficient acclimatization or pharmaceutical prophylaxis as road connectivity develops in the Himalayan region of Nepal. Our study connects ascent rate with prevalence and severity of acute mountain sickness (AMS) among patients admitted to the emergency ward of the Mustang district hospital in Nepal. A register-based, cross-sectional study was conducted between June 2018 and June 2019 to explore associations of Lake Louise scores with ascent profile, sociodemographic characteristics, and comorbidities using chi-square test, t-test, and Bayesian logistic regression. Of 105 patients, incidence of AMS was 74%, of which 61%, 36%, and 3% were mild, moderate, and severe cases, respectively. In the Bayesian-ordered logistic model of AMS severity, ascent rate (odds ratio 3.13) and smoking (odds ratio 0.16) were significant at a 99% credible interval. Based on the model-derived counterfactual, the risk of developing moderate or severe AMS for a middle-aged, non-smoking male traveling from Pokhara to Muktinath (2978m altitude gain) in a single day is twice that of making the ascent in three days. Ascent rate was strongly associated with the likelihood of developing severe AMS among travellers with AMS symptoms visiting Mustang Hospital's Emergency Ward.

Association of Pre-existing Mental Health Conditions with Acute Mountain Sickness at Everest Base Camp.

Hüfner, Katharina, Fabio Caramazza, Evelyn R. Pircher Nöckler, Agnieszka E. Stawinoga, Paolo Fusar-Poli, Sanjeeb S. Bhandari, Buddha Basnyat, Monika Brodmann Maeder, Giacomo Strapazzon, Iztok Tomazin, Ken Zafren, Hermann Brugger, and Barbara Sperner-Unterweger. Association of pre-existing mental health conditions with acute mountain sickness at Everest Base Camp. High Alt Med Biol. 23:338-344, 2022. Background: Mental health disorders are common, but limited data are available regarding the number of people with a past medical history of psychiatric diagnoses going to high altitude (HA). It is also unknown whether mental health conditions are associated with an increased risk of acute mountain sickness (AMS). Methods: We analyzed data from a previous study at Everest Base Camp. Participants self-reported their past medical history and history of substance use and had a brief history taken by a physician. AMS was assessed using the self-reported 2018 Lake Louise AMS Score. Results: Eighty-five participants (66 men and 19 women, age 38 ± 9 years) were included. When questioned by a physician, 28 participants reported prior diagnoses or symptoms compatible with depression (23%), anxiety disorder (6%), post-traumatic stress disorder (1%), and psychosis/psychotic experiences (9%). The prevalence of psychiatric diagnoses in the past medical history was much lower in the self-reported data (2/85) compared to data obtained via physician assessment (28/85). Increased risks of AMS were associated with a past medical history of anxiety disorder (odds ratio [OR] 22.7; confidence interval [95% CI] 2.3-220.6; p < 0.001), depression (OR 3.6; 95% CI 1.2-11.2; p = 0.022), and recreational drug use ever (OR 7.3; 95% CI 1.5-35.5; p = 0.006). Conclusions: Many people who travel to HA have a past medical history of mental health conditions. These individuals have an increased risk of scoring positive for AMS on the Lake Louise Score compared with people without a history of mental health conditions.

Matrix metalloproteinase-9 and substance-P as predictors for early-stage diagnosis of acute mountain sickness

IntroductionAlthough acute mountain sickness (AMS) can be a life-threatening condition, early diagnosis is difficult due to vague and non-specific symptoms. The aim of this study is to investigate biochemical markers that can detect high-altitude diseases in advance. Eight different biomarkers (BNP, HIF-1α, NGAL, MMP-3, MMP-9, SESN2, substance P (SP), and U-II) were studied, and their relationship with AMS was investigated. MethodsOf the 84 mountaineers who participated in the mountaineering training organized by the Turkish Mountaineering Federation in the Rize Kaçkar Mountains in 2018, 52 volunteered to participate in the study. Twelve hours after the participants reached an altitude of 2200 m (exposed to moderate hypoxia), their vital parameters were measured, and blood samples were taken for biochemistry tests. Vital signs and Lake Louise (LL) AMS scores were recorded every 24 h during the following 72 h. The participants were divided into two groups according to their LL scores: those with AMS and those without (AMS+ and AMS −), and the vital parameters and biomarker levels of both groups were compared and evaluated. ResultsOf the volunteers participating in the study, 35 (67.3%) were male and 17 (32.7%) were female, although there was no gender difference in terms of susceptibility to AMS. Among the investigated markers in the AMS + group, MMP-9 and SP were statistically significantly higher (p = 0.037 and p = 0.038, respectively). There were no statistical differences between AMS− and AMS+ groups with regard to heart rate, oxygen saturation, and systolic and diastolic blood pressure values (p = 0.507, p = 0.929, p = 0.955, p = 0.572, respectively). ConclusionThere were significant differences between the AMS− and AMS+ groups in terms of MMP-9 and SP. However, differences in physical indexes between the groups were not statistically significant. This could provide objective indexes for scanning and screening individuals susceptible to AMS in the early stages of rapid ascending.

Thickened Retinal Nerve Fiber Layers Associated With High-Altitude Headache.

Purpose: This study aimed to quantify the different quadrants of the optic nerve head (ONH) and macular parameters and their changes during exposure to high altitude, and to assess their correlation with high-altitude headache (HAH). Methods: Spectral-domain optical coherence tomography (OCT) was used to quantify changes in the retinal structure in 109 healthy subjects during acute exposure to high altitude (3,700 m). Self-reported symptoms of HAH and acute mountain sickness AMS were assessed using Lake Louise Score (LLS), alongside measurements of physiological parameters (oxygen saturation [SpO2], heart rate [HR], hemoglobin level [Hb], and red blood cell [RBC] count). Measurements were taken before and after exposure to the high-altitude environment. The correlations of these parameters and changes at ONH were examined. Results: With the exposure to high altitude, the incidence of AMS was 44.0% and the frequency of HAH was 67.0% (54.1% mild, 12.9% moderate-severe). As for systemic parameters measured at high altitude, the participants exhibited significantly lower SpO2, higher resting HR, higher Hb, and a higher RBC (all p < 0.05). Key stereometric parameters used to describe ONH [superior, inferior, nasal, temporal, and mean retinal nerve fiber layer (RNFL) thickness] and macula (macular thickness) increased at high altitude compared with baseline. Most parameters of ONH changed, especially superior, inferior, and mean RNFL thickness (p < 0.05). There was a significant correlation between the ratios of RNFL at ONH and HAH [mean thickness (r = 0.246, p = 0.01); inferior (r = 0.216, p = 0.02); nasal (r = 0.193, p = 0.04)]. No associations between parameters of ONH and AMS or LLS were observed. Conclusion: The high-altitude environment can increase RNFL thickness at ONH. Furthermore, we found that the ratios of mean thickness, inferior area, and nasal area correlated positively with HAH, which provides new insights for understanding of the underlying pathological mechanisms of high-altitude retinopathy (HAR).

Preliminary Intermittent Hypoxia Training Alleviates the Damage of Sustained Normobaric Hypoxia on Human Hematological Indexes and Cerebral White Matter.

Zhang, Guangbo, Yanzhao Zhou, Zhengtao Cao, Xiang Cheng, Xiangpei Yue, Tong Zhao, Ming Zhao, Yongqi Zhao, Ming Fan, and Lingling Zhu. Preliminary intermittent hypoxia training alleviates the damage of sustained normobaric hypoxia on human hematological indexes and cerebral white matter. High Alt Med Biol. 23:273-283, 2022. Background: We aimed to examine the effects of preliminary intermittent hypoxia training (IHT) on human hematological indexes and cerebral white matter (WM) after exposure to a simulated altitude of 4,300 m. Methods: We recruited 20 young healthy volunteers. Participants were then randomized to either the IHT group (n = 10) or the control group (n = 10). We measured the physiological function of the control group at sea level and after exposure to a simulated altitude of 4,300 m, respectively. The IHT group performed the above tests at three time points: before and after hypoxia training, and after exposure to a simulated altitude of 4,300 m, respectively. Results: We found that mean SpO2 during day 10 of hypoxia training showed a significant increase compared with mean SpO2 on day 1 (88.3% ± 1.5% vs. 90.0% ± 1.6%, p < 0.05), and erythrocyte P50 of post-training was significantly increased compared with pretraining (37.8 ± 2.9 mmHg vs. 45.9 ± 6.4 mmHg, p < 0.05). Mean SpO2 measures after acute exposure to high altitude exhibited a significant difference, with the IHT group showing significantly greater SpO2 than the control group (73.8% ± 3.7% vs. 77.4% ± 3.2%, p < 0.05), and the Lake Louise Score was also lower than the control group (2.55 ± 2.1 vs. 6.67 ± 2.5, p < 0.05). After daily IHT, brain-derived neurotrophic factor plasma levels of participants in the IHT group did not change but significantly increased in response to high-altitude hypoxia (103.5% ± 70.4% vs. 29.7% ± 73.2%, p < 0.05). Interleukin-10 (IL-10) plasma level did not change before and after IHT in the IHT group, whereas the IL-10 plasma level of the control group after high-altitude exposure was significantly higher. Furthermore, we found that fractional anisotropy values in the left corticospinal tract and splenium of the corpus callosum in the IHT group were significantly higher than those in the control group after high-altitude hypoxia. Conclusions: These results demonstrate that IHT alleviates the damage of sustained normobaric hypoxia on human hematological indexes and cerebral WM.

Contribution of Hypoxic Exercise Testing to Predict High-Altitude Pathology: A Systematic Review.

Altitude travelers are exposed to high-altitude pathologies, which can be potentially serious. Individual susceptibility varies widely and this makes it difficult to predict who will develop these complications. The assessment of physiological adaptations to exercise performed in hypoxia has been proposed to help predict altitude sickness. The purpose of this review is to evaluate the contribution of hypoxic exercise testing, achieved in normobaric conditions, in the prediction of severe high-altitude pathology. We performed a systematic review using the databases PubMed, Science Direct and Embase in October 2021 to collect studies reporting physiological adaptations under hypoxic exercise testing and its interest in predicting high-altitude pathology. Eight studies were eligible, concerning 3558 patients with a mean age of 46.9 years old, and a simulated mean altitude reaching of 5092 m. 597 patients presented an acute mountain sickness during their altitude travels. Three different protocols of hypoxic exercise testing were used. Acute mountain sickness was defined using Hackett’s score or the Lake Louise score. Ventilatory and cardiac responses to hypoxia, desaturation in hypoxia, cerebral oxygenation, core temperature, variation in body mass index and some perceived sensations were the highlighted variables associated with acute mountain sickness. A decision algorithm based on hypoxic exercise tests was proposed by one team. Hypoxic exercise testing provides promising information to help predict altitude complications. Its interest should be confirmed by different teams.

Association of Genes of the NO Pathway with Altitude Disease and Hypoxic Pulmonary Hypertension.

Chronic intermittent hypoxia leads to high-altitude pulmonary hypertension, which is associated with high asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthesis. Therefore, we aimed to understand the relation of single nucleotide polymorphisms in this pathway to high-altitude pulmonary hypertension (HAPH). We genotyped 69 healthy male Chileans subjected to chronic intermittent hypoxia. Acclimatization to altitude was determined using the Lake Louise Score and the presence of acute mountain sickness. Echocardiography was performed after six months in 24 individuals to estimate pulmonary arterial pressure. The minor allele of dimethylarginine dimethylaminohydrolase (DDAH)1 rs233112 was associated with high-baseline plasma ADMA concentration, while individuals homozygous for the major allele of DDAH2 rs805304 had a significantly greater increase in ADMA during chronic intermittent hypoxia. The major allele of alanine glyoxylate aminotransferase-2 (AGXT2) rs37369 was associated with a greater reduction of plasma symmetric dimethylarginine (SDMA). Several genes were associated with high-altitude pulmonary hypertension, and the nitric oxide synthase (NOS)3 and DDAH2 genes were related to acute mountain sickness. In conclusion, DDAH1 determines baseline plasma ADMA, while DDAH2 modulates ADMA increase in hypoxia. AGXT2 may be up-regulated in hypoxia. Genomic variation in the dimethylarginine pathway affects the development of HAPH and altitude acclimatization.

Different physiopsychological changes between AMS-susceptible and AMS-resistant pre-selected Antarctic expeditioners in Tibet

Through dynamically monitoring changes of acute mountain sickness (AMS) occurrences, cardiopulmonary function and mood states from Shanghai (4 m) to Lhasa (3650 m) and Yambajan (4300 m), Tibet, we obtained physiopsychological data of the 37th Chinese Antarctic pre-selected expeditioners for Kunlun Station. Through analyzing different physiopsychological changes between AMS-susceptible (AMS-S) and AMS-resistant (AMS-R) expeditioners, we would explore indicators to screen hypoxia-susceptible expeditioners. According to AMS occurrences evaluated by Lake Louise Score (LLS) in Yambajan, we divided the expeditioners (n=24, 31.92±5.76 a) into AMS-S and AMS-R groups. Using a series of medical instruments and questionnaires, we monitored their cardiopulmonary function and mood states, and analyzed the differences of physiopsychological parameters between AMS-S and AMS-R groups. Compared with Shanghai, when expeditioners arrived in Yambajan, in both AMS-S and AMS-R groups, oxygen saturation (SpO2) significantly decreased, and blood pressure significantly increased (P Citation : Wu X P, Liu S Y, Wang X, et al. Different physiopsychological changes between AMS-susceptible and AMS-resistant pre-selected Antarctic expeditioners in Tibet. Adv Polar Sci, 2021, 32(3): 239-247, doi: 10.13679/j.advps.2021.0010