Patent Foramen Ovale and Acute Mountain Sickness.

Acute mountain sickness (AMS) commonly plagues people who travel to high altitude and can be life threatening. Clinically, AMS is defined by a constellation of symptoms as outlined in the Lake Louise Criteria. The underlying etiology is thought to be related to a decrease in partial pressure of oxygen leading to tissue hypoxia. Patent foramen ovale (PFO) has been postulated to play a role in AMS through right-to-left shunt, which can worsen hypoxemia. Recent data demonstrate a higher prevalence of PFO in hikers with AMS. Future studies are needed to further elucidate the relationship between PFO and AMS.

Curcumin-mediated enhancement of lung barrier function in rats with high-altitude-associated acute lung injury via inhibition of inflammatory response.

BACKGROUND: Exposure to a hypobaric hypoxic environment at high altitudes can lead to lung injury. In this study, we aimed to determine whether curcumin (Cur) could improve lung barrier function and protect against high-altitude-associated acute lung injury. METHODS: Two hundred healthy rats were randomly divided into standard control, high-altitude control (HC), salidroside (40 mg/kg, positive control), and Cur (200 mg/kg) groups. Each group was further divided into five subgroups. Basic vital signs, lung injury histopathology, routine blood parameters, plasma lactate level, and arterial blood gas indicators were evaluated. Protein and inflammatory factor (tumor necrosis factor α (TNF-α), interleukin [IL]-1ß, IL-6, and IL-10) concentrations in bronchoalveolar lavage fluid (BALF) were determined using the bicinchoninic acid method and enzyme-linked immunosorbent assay, respectively. Inflammation-related and lung barrier function-related proteins were analyzed using immunoblotting. RESULTS: Cur improved blood routine indicators such as hemoglobin and hematocrit and reduced the BALF protein content and TNF-α, IL-1ß, and IL-6 levels compared with those in the HC group. It increased IL-10 levels and reduced pulmonary capillary congestion, alveolar hemorrhage, and the degree of pulmonary interstitial edema. It increased oxygen partial pressure, oxygen saturation, carbonic acid hydrogen radical, and base excess levels, and the expression of zonula occludens 1, occludin, claudin-4, and reduced carbon dioxide partial pressure, plasma lactic acid, and the expression of phospho-nuclear factor kappa. CONCLUSIONS: Exposure to a high-altitude environment for 48 h resulted in severe lung injury in rats. Cur improved lung barrier function and alleviated acute lung injury in rats at high altitudes.

A Rare Case of High-Altitude Polycythemia Complicated by Spontaneous Splenic Rupture.

Wang, Bowen, Mengjia Peng,, Liheng Jiang,, Fei Fang,, Juan Wang,, Yan Li,, Ruichen Zhao,, and Yuliang Wang,. A Rare Case of High-Altitude Polycythemia Complicated by Spontaneous Splenic Rupture. High Alt Med Biol. 25:247-250, 2024.-High-altitude polycythemia, a condition characterized by an increase in red blood cellRBC mass, can occur after prolonged exposure to high altitudes. While several studies have explored the complications associated with high-altitude polycythemia, there is currently no literature available on spontaneous spleen rupture caused by high-altitude polycythemia. Here, we reported a case of acute abdominal pain and hemodynamic instability in a 36-year-old male who had been residing at high altitude for 6 years, without any recent history of trauma. Computed tomography imaging revealed significant fluid accumulation in the abdomen, and a tear of the splenic capsule was identified during the following laparotomy. Subsequent evaluations confirmed the presence of polycythemia secondary to prolonged high-altitude exposure as the underlying etiology. This case served as an important reminder that high-altitude polycythemia could lead to serious complications, such as spontaneous spleen rupture. Clinicians should be aware of this potential complication and consider it in the differential diagnosis of patients presenting with abdominal pain and hemodynamic instability in this population.

Intermittent high altitude hypoxia induced liver and kidney injury leading to hyperuricemia.

About 140 million people worldwide live at an altitude above 2500 m. Studies have showed an increase of the incidence of hyperuricemia among plateau populations, but little is known about the possible mechanisms. This study aims to assess the effects of high altitude on hyperuricemia and explore the corresponding mechanisms at the histological, inflammatory and molecular levels. This study finds that intermittent hypobaric hypoxia (IHH) exposure results in an increase of serum uric acid level and a decrease of uric acid clearance rate. Compared with the control group, the IHH group shows significant increases in hemoglobin concentration (HGB) and red blood cell counts (RBC), indicating that high altitude hyperuricemia is associated with polycythemia. This study also shows that IHH exposure induces oxidative stress, which causes the injury of liver and renal structures and functions. Additionally, altered expressions of organic anion transporter 1 (OAT1) and organic cation transporter 1 (OCT1) of kidney have been detected in the IHH exposed rats. The adenosine deaminase (ADA) expression levels and the xanthione oxidase (XOD) and ADA activity of liver of the IHH exposure group have significantly increased compared with those of the control group. Furthermore, the spleen coefficients, IL-2, IL-1ß and IL-8, have seen significant increases among the IHH exposure group. TLR/MyD88/NF-κB pathway is activated in the process of IHH induced inflammatory response in joints. Importantly, these results jointly show that IHH exposure causes hyperuricemia. IHH induced oxidative stress along with liver and kidney injury, unusual expression of the uric acid synthesis/excretion regulator and inflammatory response, thus suggesting a potential mechanism underlying IHH-induced hyperuricemia.

Altitude illnesses.

Millions of people visit high-altitude regions annually and more than 80 million live permanently above 2,500 m. Acute high-altitude exposure can trigger high-altitude illnesses (HAIs), including acute mountain sickness (AMS), high-altitude cerebral oedema (HACE) and high-altitude pulmonary oedema (HAPE). Chronic mountain sickness (CMS) can affect high-altitude resident populations worldwide. The prevalence of acute HAIs varies according to acclimatization status, rate of ascent and individual susceptibility. AMS, characterized by headache, nausea, dizziness and fatigue, is usually benign and self-limiting, and has been linked to hypoxia-induced cerebral blood volume increases, inflammation and related trigeminovascular system activation. Disruption of the blood-brain barrier leads to HACE, characterized by altered mental status and ataxia, and increased pulmonary capillary pressure, and related stress failure induces HAPE, characterized by dyspnoea, cough and exercise intolerance. Both conditions are progressive and life-threatening, requiring immediate medical intervention. Treatment includes supplemental oxygen and descent with appropriate pharmacological therapy. Preventive measures include slow ascent, pre-acclimatization and, in some instances, medications. CMS is characterized by excessive erythrocytosis and related clinical symptoms. In severe CMS, temporary or permanent relocation to low altitude is recommended. Future research should focus on more objective diagnostic tools to enable prompt treatment, improved identification of individual susceptibilities and effective acclimatization and prevention options.

Bawei Chenxiang Wan ameliorates right ventricular hypertrophy in rats with high altitude heart disease by SIRT3-HIF1α-PDK/PDH signaling pathway improving fatty acid and glucose metabolism.

BACKGROUND: Bawei Chenxiang Wan (BCW) is among the most effective and widely used therapies for coronary heart disease and angina pectoris in Tibet. However, whether it confers protection through a right-ventricle (RV) myocardial metabolic mechanism is unknown. METHODS: Male Sprague-Dawley rats were orally administrated with BCW, which was injected concurrently with a bolus of Sugen5416, and subjected to hypoxia exposure (SuHx; 5000 m altitude) for 4 weeks. Right ventricular hypertrophy (RVH) in high-altitude heart disease (HAHD) was assessed using Fulton's index (FI; ratio of RV to left ventricle + septum weights) and heart-weight-to-body-weight ratio (HW/BW). The effect of therapeutic administration of BCW on the RVH hemodynamics was assessed through catheterization (mean right ventricular pressure and mean pulmonary artery pressure (mRVP and mPAP, respectively)). Tissue samples were used to perform histological staining, and confirmatory analyses of mRNA and protein levels were conducted to detect alterations in the mechanisms of RVH in HAHD. The protective mechanism of BCW was further verified via cell culture. RESULTS: BCW considerably reduced SuHx-associated RVH, as indicated by macro morphology, HW/BW ratio, FI, mPAP, mRVP, hypertrophy markers, heart function, pathological structure, and myocardial enzymes. Moreover, BCW can alleviate the disorder of glucose and fatty acid metabolism through upregulation of carnitine palmitoyltransferase1ɑ, citrate synthase, and acetyl-CoA and downregulation of glucose transport-4, phosphofructokinase, and pyruvate, which resulted in the reduced levels of free fatty acid and lactic acid and increased aerobic oxidation. This process may be mediated via the regulation of sirtuin 3 (SIRT3)-hypoxia-inducible factor 1α (HIF1α)-pyruvate dehydrogenase kinase (PDK)/pyruvate dehydrogenase (PDH) signaling pathway. Subsequently, the inhibition of SIRT3 expression by 3-TYP (a selective inhibitor of SIRT3) can reverse substantially the anti-RVH effect of BCW in HAHD, as indicated by hypertrophy marker and serum myocardial enzyme levels. CONCLUSIONS: BCW prevented SuHx-induced RVH in HAHD via the SIRT3-HIF1ɑ-PDK/PDH signaling pathway to alleviate the disturbance in fatty acid and glucose metabolism. Therefore, BCW can be used as an alternative drug for the treatment of RVH in HAHD.

Lactobacillus delbrueckii subsp. bulgaricus Alleviates Acute Injury in Hypoxic Mice.

Acute mountain sickness (AMS) is a common ailment in high-altitude areas caused by the body's inadequate adaptation to low-pressure, low-oxygen environments, leading to organ edema, oxidative stress, and impaired intestinal barrier function. The gastrointestinal tract, being the first to be affected by ischemia and hypoxia, is highly susceptible to injury. This study investigates the role of Lactobacillus delbrueckii subsp. bulgaricus in alleviating acute hypoxic-induced intestinal and tissue damage from the perspective of daily consumed lactic acid bacteria. An acute hypoxia mouse model was established to evaluate tissue injury, oxidative stress, inflammatory responses, and intestinal barrier function in various groups of mice. The results indicate that strain 4L3 significantly mitigated brain and lung edema caused by hypoxia, improved colonic tissue damage, and effectively increased the content of tight junction proteins in the ileum, reducing ileal permeability and alleviating mechanical barrier damage in the intestines due to acute hypoxia. Additionally, 4L3 helped to rebalance the intestinal microbiota. In summary, this study found that Lactobacillus delbrueckii subsp. bulgaricus strain 4L3 could alleviate acute intestinal damage caused by hypoxia, thereby reducing hypoxic stress. This suggests that probiotic lactic acid bacteria that exert beneficial effects in the intestines may alleviate acute injury under hypoxic conditions in mice, offering new insights for the prevention and treatment of AMS.

Does Lake Louise questionnaire interpret high-altitude headache as acute mountain sickness? Experience in the western Himalayas.

BACKGROUND OBJECTIVES: High-altitude headache (HAH) and headache in acute mountain sickness (AMS) are common among lowlanders ascending to the high altitude and are often confused with one another. A pilot study was undertaken to analyze HAH and AMS cases in Indian lowlanders ascending to Leh city (3500 m) in western Himalayas. METHODS: A total number of 1228 Indian lowlanders, who ascended (fresh and re-inductees) by air and acclimatized, participated in this pilot study. The intensity of headache was assessed by the Visual Analogue Score. The parameters of HAH as per the International Classification of Headache Disorders-3 and 2018 Revised Lake Louise Questionnaire (LLQ) were used to differentiate HAH and AMS. RESULTS: Out of 1228 cases, 78 (6.4%) cases had headache, of which 24 (1.95%) cases were HAH only, 40 (3.25%) cases AMS only and 14 (1.14%) cases were defined as both HAH and AMS. There was a significant difference in heart rate [F (2,51) = (4.756), P =0.01] between these groups. It also showed a difference in the correlation between the parameters within the groups. The Odd's Ratio of AMS in fresh and re-inductees was found to be 4.5 and for HAH it was 4.33. INTERPRETATION CONCLUSIONS: The findings of this study suggest that LLQ has a tendency of overestimating AMS by including HAH cases. Furthermore differential parameters exhibit differences when AMS and HAH are considered separately. Re-inductees showed a lower incidence of HAH and AMS.

[Mechanism of IL-17 Signaling Pathway in Spleen Inflammatory Response Induced by Altitude Hypoxia in Mice]. / IL-17ä¿¡å·é€šè·¯åœ¨é«˜åŽŸä½Žæ°§è¯±å¯¼å°é¼ è„¾è„ç‚Žç—‡ååº”çš„ä½œç”¨æœºåˆ¶.

Objective: To explore the mechanism of spleen tissue inflammatory response induced by altitude hypoxia in mice. Methods: C57BL/6 mice were randomly assigned to a plain, i.e., low-altitude, normoxia group and an altitude hypoxia group, with 5 mice in each group. In the plain normoxia group, the mice were kept in a normoxic environment at the altitude of 400 m above sea level (with an oxygen concentration of 19.88%). The mice in the altitude hypoxia group were kept in an environment at the altitude of 4200 m above sea level (with an oxygen concentration of 14.23%) to establish the animal model of altitude hypoxia. On day 30, spleen tissues were collected to determine the splenic index. HE staining was performed to observe the histopathological changes in the spleen tissues of the mice. Real time fluorogenic quantitative PCR (RT-qPCR) and Western blot were conducted to determine the mRNA and protein expressions of interleukin (IL)-6, IL-12, and IL-1ß in the spleen tissue of the mice. High-throughput transcriptome sequencing was performed with RNA sequencing (RNA-seq). KEGG enrichment analysis was performed for the differentially expressed genes (DEGs). The DEGs in the key pathways were verified by RT-qPCR. Results: Compared with the plain normoxia group, the mice exposed to high-altitude hypoxic environment had decreased spleen index (P<0.05) and exhibited such pathological changes as decreased white pulp, enlarged germinal center, blurred edge, and venous congestion. The mRNA and protein expression levels of IL-6, IL-12, and IL-1ß in the spleen tissue of mice in the altitude hypoxia group were up-regulated (P<0.05). According to the results of transcriptome sequencing and KEGG pathway enrichment analysis, 4218 DEGs were enriched in 178 enrichment pathways (P<0.05). DEGs were significantly enriched in multiple pathways associated with immunity and inflammation, such as T cell receptor signaling pathway, TNF signaling pathway, and IL-17 signaling pathway (P<0.05) in the spleen of mice exposed to high-altitude hypoxic environment. Among them, IL-17 signaling pathway and the downstream inflammatory factors were highly up-regulated (P<0.05). Compared with the plain normoxia group, the mRNA expression levels of key genes in the IL-17 signaling pathway, including IL-17, IL-17R, and mitogen-activated protein kinase genes (MAPKs), and the downstream inflammatory factors, including matrix metallopeptidase 9 (MMP9), S100 calcium binding protein A8 gene (S100A8), S100 calcium binding protein A9 gene (S100A9), and tumor necrosis factor α (TNF-α), were up-regulated or down-regulated (P<0.05) in the altitude hypoxia group. According to the validation of RT-qPCR results, the mRNA expression levels of DEGs were consistent with the RNA-seq results. Conclusion: Altitude hypoxia can induce inflammatory response in the mouse spleen tissue by activating IL-17 signaling pathway and promoting the release of downstream inflammatory factors.

Acute changes in cardiac dimensions, function, and longitudinal mechanics in healthy individuals with and without high-altitude induced pulmonary hypertension at 4559 m.

BACKGROUND: High-altitude pulmonary hypertension (HAPH) has a prevalence of approximately 10%. Changes in cardiac morphology and function at high altitude, compared to a population that does not develop HAPH are scarce. METHODS: Four hundred twenty-one subjects were screened in a hypoxic chamber inspiring a FiO2  = 12% for 2 h. In 33 subjects an exaggerated increase in systolic pulmonary artery pressure (sPAP) could be confirmed in two independent measurements. Twenty nine of these, and further 24 matched subjects without sPAP increase were examined at 4559 m by Doppler echocardiography including global longitudinal strain (GLS). RESULTS: SPAP increase was higher in HAPH subjects (∆ = 10.2 vs. ∆ = 32.0 mm Hg, p < .001). LV eccentricity index (∆ = .15 vs. ∆ = .31, p = .009) increased more in HAPH. D-shaped LV (0 [0%] vs. 30 [93.8%], p = .00001) could be observed only in the HAPH group, and only in those with a sPAP ≥50 mm Hg. LV-EF (∆ = 4.5 vs. ∆ = 6.7%, p = .24) increased in both groups. LV-GLS (∆ = 1.2 vs. ∆ = 1.1 -%, p = .60) increased slightly. RV end-diastolic (∆ = 2.20 vs. ∆ = 2.7 cm2 , p = .36) and end-systolic area (∆ = 2.1 vs. ∆ = 2.7 cm2 , p = .39), as well as RA end-systolic area index (∆ = -.9 vs. ∆ = .3 cm2 /m2 , p = .01) increased, RV-FAC (∆ = -2.9 vs. ∆ = -4.7%, p = .43) decreased, this was more pronounced in HAPH, RV-GLS (∆ = 1.6 vs. ∆ = -.7 -%, p = .17) showed marginal changes. CONCLUSIONS: LV and LA dimensions decrease and left ventricular function increases at high-altitude in subjects with and without HAPH. RV and RA dimensions increase, and RV longitudinal strain increases or remains unchanged in subjects with HAPH. Changes are negligible in those without HAPH.

A Case of High-Altitude Renal Syndrome.

Wang, Si-Yang, Jun Liang, and Jing-Hong Zhao. A Case of High-Altitude Renal Syndrome. High Alt Med Biol. 00:000-000, 2024.-Epidemiological studies have confirmed that high-altitude exposure increases the risk of proteinuria. The concept of high-altitude renal syndrome (HARS) was proposed in 2011. HARS is a group of clinical syndromes consisting of high-altitude polycythemia, hyperuricemia, systemic hypertension, and microalbuminuria. At present, no standardized and unified treatment methods of HARS have been proposed. We report a case of HARS without other organ involvement in a young man exposed to high altitude. Decreasing the red blood cell count and hemodynamic changes as soon as possible may be of great importance for reducing proteinuria. In addition, angiotensin receptor blockers are effective in the treatment of HARS.

High altitude retinopathy: An overview and new insights.

High altitude retinopathy (HAR) is a common ocular disorder that occurs on ascent to high altitude. There are many clinical symptoms, retinal vascular dilatation, retinal edema and hemorrhage are common. These usually do not or slightly affect vision; rarely, severe cases develop serious or permanent vision loss. At present, the research progress of HAR mainly focuses on hemodynamic changes, blood-retinal barrier damage, oxidative stress and inflammatory response. Although the related studies on HAR are limited, it shows that HAR still belongs to hypoxia, and hypobaric hypoxia plays an aggravating role in promoting the development of the disease. Various studies have demonstrated the correlation of HAR with acute mountain sickness (AMS) and high-altitude cerebral edema (HACE), so a deeper understanding of HAR is important. The slow ascent rates and ascent altitude are the key to preventing any altitude sickness. Research on traditional chinese medicine (TCM) and western medicine has been gradually carried out. Further exploration of the pathogenesis and prevention strategies of HAR will provide better guidance for doctors and high-altitude travelers.

Exercise and hypoxia-induced hypercoagulability is counterbalanced in women in part by decreased platelet reactivity.

Hypoxia plays an important role in several pathologies, e.g. chronic obstructive pulmonary disease and obstructive sleep apnea syndrome, and is linked to an increased thrombosis risk. Furthermore, oxygen deprivation is associated with hypercoagulability. In this study, we investigated the effect of gender and exercise on the coagulation potential under hypoxic conditions at high altitude by assessing thrombin generation (TG) and platelet activation. Hereto, ten healthy volunteers were included (50 % male, median age of 27.5 years). The measurements were conducted first at sea level and then twice at high altitude (3883 m), first after a passive ascent by cable car and second after an active ascent by a mountain hike. As expected, both the passive and active ascent resulted in a decreased oxygen saturation and an increased heart rate at high altitude. Acute mountain sickness symptoms were observed independently of the ascent method. After the active ascent, platelet, white blood cell and granulocyte count were increased, and lymphocytes were decreased, without a gender-related difference. FVIII and von Willebrand factor were significantly increased after the active ascent for both men and women. Platelet activation was reduced and delayed under hypobaric conditions, especially in women. TG analysis showed a prothrombotic trend at high altitude, especially after the active ascent. Women had a hypercoagulable phenotype, compared to men at all 3 timepoints, indicated by a higher peak height and endogenous thrombin potential (ETP), and shorter lag time and time-to-peak. In addition, ETP and peak inhibition by thrombomodulin was lower in women after the active ascent, compared to men. Interestingly, data normalisation for subject baseline values indicated an opposing effect of altitude-induced hypoxia on α2-macroglobulin levels and TG lag time between men and women, decreasing in men and increasing in women. We conclude that hypoxia increases TG, as well as FVIII and VWF levels in combination with exercise. In contrast, platelets lose their responsiveness at high altitude, which is most pronounced after heavy exercise. Women had a more pronounced prothrombotic phenotype compared to men, which we theorize is counterbalanced under hypobaric conditions by decreased platelet activation.

The Effect of High-Altitude Hypoxia on Neuropsychiatric Functions.

Liu, Bo, Minlan Yuan, Mei Yang, Hongru Zhu, and Wei Zhang. The effect of high-altitude hypoxia on neuropsychiatric functions. High Alt Med Biol. 25:26-41, 2024. Background: In recent years, there has been a growing popularity in engaging in activities at high altitudes, such as hiking and work. However, these high-altitude environments pose risks of hypoxia, which can lead to various acute or chronic cerebral diseases. These conditions include common neurological diseases such as acute mountain sickness (AMS), high-altitude cerebral edema, and altitude-related cerebrovascular diseases, as well as psychiatric disorders such as anxiety, depression, and psychosis. However, reviews of altitude-related neuropsychiatric conditions and their potential mechanisms are rare. Methods: We conducted searches on PubMed and Google Scholar, exploring existing literature encompassing preclinical and clinical studies. Our aim was to summarize the prevalent neuropsychiatric diseases induced by altitude hypoxia, the potential pathophysiological mechanisms, as well as the available pharmacological and nonpharmacological strategies for prevention and intervention. Results: The development of altitude-related cerebral diseases may arise from various pathogenic processes, including neurovascular alterations associated with hypoxia, cytotoxic responses, activation of reactive oxygen species, and dysregulation of the expression of hypoxia inducible factor-1 and nuclear factor erythroid 2-related factor 2. Furthermore, the interplay between hypoxia-induced neurological and psychiatric changes is believed to play a role in the progression of brain damage. Conclusions: While there is some evidence pointing to pathophysiological changes in hypoxia-induced brain damage, the precise mechanisms responsible for neuropsychiatric alterations remain elusive. Currently, the range of prevention and intervention strategies available is primarily focused on addressing AMS, with a preference for prevention rather than treatment.

High-Altitude Pulmonary Edema Combined with Spontaneous Pneumomediastinum: A Case Report.

Background: High-altitude pulmonary edema (HAPE) is a serious life-threatening disease that occurs after rapid ascent to high altitude; its main early-stage presentations include fatigue, headache, low-grade fever, dyspnea, and cough. X-ray and computed tomography (CT) images show pulmonary shadows and patches, which may be localized (initial right lung field predomination) or generalized to the bilateral lung base. Case Presentation: In this report, we present a case of a 25-year-old man diagnosed with HAPE combined with spontaneous pneumomediastinum. After a quick descent and effective medical treatment, this patient made a full recovery. The case may provide helpful information for the prevention and treatment of this disease since an increased number of people, especially young men, currently travel and work at high altitudes. Conclusion: After accurate clinical diagnosis with the help of CT or X-ray, immediate descent and appropriate oxygen supplementation are the most effective treatments for HAPE at high altitude.

High-Altitude Pulmonary Edema in Women: A Scoping Review-UIAA Medical Commission Recommendations.

Pichler Hefti, Jacqueline, Dominique Jean, Alison Rosier, Mia Derstine, David Hillebrandt, Lenka Horakova, Linda E. Keyes, Kaste Mateikaite-Pipiriene, Peter Paal, Marija Andjelkovic, Beth Beidlemann, and Susi Kriemler. High-altitude pulmonary edema in women: a scoping review-UIAA Medical Commission Recommendations. High Alt Med Biol. 24:268-273, 2023. Background: High-altitude pulmonary edema (HAPE) can occur >2,500-3,000 m asl and is a life-threatening medical condition. This scoping review aims to summarize the current data on sex differences in HAPE. Methods: The International Climbing and Mountaineering Federation (UIAA) Medical Commission convened an international author team to review women's health issues at high altitude. Pertinent literature from PubMed and Cochrane was identified by keyword search combinations (including HAPE), with additional publications found by hand search. The primary search focus was for original articles that included minimum one woman and at least a rudimentary subgroup analysis. Results: The literature search yielded 7,165 articles, 416 of which were relevant for HAPE, and 7 of which were ultimately included here. Six were case series, consistently reporting a lower HAPE prevalence in women. The one retrospective case-control study reported male HAPE prevalence at 10/100,000 and female at 0.74/100,000. No studies were identified that directly compared sex differences in the prevalence of HAPE. No published data was found for topics other than epidemiology. Conclusions: Few studies and associated methodological limitations allow few conclusions to be drawn. Incidence of HAPE may be lower in women than in men. We speculate that besides physiological aspects, behavioral differences may contribute to this potential sex difference.

High-Altitude Exposure and Cerebral Venous Thrombosis: An Updated Systematic Review.

Kharel, Sanjeev, Suraj Shrestha, Samriddha Raj Pant, Suman Acharya, Amit Sharma, Santosh Baniya, and Sanjeeb S. Bhandari. High-altitude exposure and cerebral venous thrombosis: an updated systematic review. High Alt Med Biol. 24:167-174, 2023. Background: High altitude (HA) may increase the risk of cerebral venous thrombosis (CVT). Differentiating it from other HA illnesses is crucial for prompt treatment and better outcomes. We aimed to summarize the clinical data, etiology, and risk factors of this poorly understood entity at an HA. Materials and Methods: A systematic literature search of various databases, including PubMed, Embase, and Google Scholar, was done using relevant keywords; cerebral venous thrombosis; HA, up to May 1, 2022. Results: A total of nine studies, including 75 cases of CVT at HA (3,000-8,848 m), with 66 males and 9 females, were included in this review. Headache and seizure were the most common clinical presentations. Smoking, drinking habits, and the use of oral contraceptive pills (OCP) were the most common risk factors for the development of CVT. Similarly, various underlying hypercoagulable states were also present among cases of CVT associated with HA exposure. Conclusion: Our review concludes that HA exposure can predispose individuals with risk factors such as preexisting hypercoagulable states, smoking, drinking habits, and use of OCP to an increased risk of CVT.

Appetite, Hypoxia, and Acute Mountain Sickness: A 10-Hour Normobaric Hypoxic Chamber Study.

Barclay, Holly, Saptarshi Mukerji, Bengt Kayser, and Jui-Lin Fan. Appetite, hypoxia and acute mountain sickness: A 10-hour normobaric hypoxic chamber study. High Alt Med Biol. 24:329-335, 2023. Background: The effects of hypoxia and acute mountain sickness (AMS) on appetite and food preferences are moot, especially during the early phase of hypoxic exposure. We examined the effects of a 10-hour hypoxic exposure on appetite and food preference. Methods: We assessed appetite (hunger, satisfaction, fullness, perceived appetite, and lost appetite), food preferences (sweet, salty, savory, and fatty), and AMS (Lake Louise score) with questionnaires in 27 healthy individuals (13 women) across 10-hour exposures to normobaric normoxia (fraction of inspired O2 [FiO2]: 0.21) and normobaric hypoxia (FiO2: 0.12, equivalent of 5,000 m) in a randomized, single-blinded manner. Results and Conclusions: Compared with normoxia, hypoxia decreased hunger and appetite (p = 0.040 and <0.001, respectively), which was mediated by a decreased desire for sweet, salty, and fatty foods (p < 0.05 for all). AMS was associated with a decreased desire for sweet (R = -0.438, p = 0.032) and salty foods (R = -0.460, p = 0.024) and greater loss of appetite (R = -0.619, p = 0.018). Our findings suggest that acute hypoxia rapidly suppresses appetite and that AMS development further amplifies anorexia. Clinical Trial Registration Number: ACTRN12618000548235.

Changes in expression levels of erythrocyte and immune-related genes are associated with high altitude polycythemia.

BACKGROUND: As a chronic mountain sickness(CMS) with the highest incidence and the greatest harm, the pathogenesis of high altitude polycythemia (HAPC) is still not fully understood. METHODS: 37 HAPC patients and 42 healthy subjects were selected from plateau, and peripheral venous blood samples were collected for transcriptome sequencing on Illumina NovaSeq platform. The sequenced data were analyzed by bioinformatics and phenotypic association analysis. RESULTS: The results showed significant differences in multiple clinical indicators including RBC and HGB et al. existed between HAPC and control. Based on the RNA-seq data, 550 genes with significant differential expression were identified in HAPC patients. GO and KEGG pathway enrichment analysis showed that the up-regulated genes were mainly enriched in processes such as erythrocyte differentiation and development and homeostasis of number of cells, while the down-regulated genes were mainly enriched in categories such as immunoglobulin production, classical pathway of complement activation and other biological processes. The coupling analysis of differential expression genes(DEGs) and pathological phenotypes revealed that 91 DEGs were in close correlation with in the phenotype of red blood cell volume distribution (width-CV and width-SD), and they were all up-regulated in HAPC and involved in the process of erythrocyte metabolism. Combined with the functional annotation of DEGs and literature survey, we found that the expression of several potential genes might be responsible for pathogenesis of HAPC. Besides, cell type deconvolution analysis result suggested that the changes in the number of some immune cell types was significantly lower in HAPC patients than control, implying the autoimmune level of HAPC patients was affected to a certain extent. CONCLUSION: This study provides an important data source for understanding the pathogenesis and screening pathogenic genes of HAPC. We found for the first time that there was a significant correlation between HAPC and the pathological phenotype of width-CV and width-SD, wherein the enriched genes were all up-regulated expressed and involved in the process of erythrocyte metabolism. Although the role of these genes needs to be further studied, the candidate genes can provide a starting point for functionally pinning down the underlying mechanism of HAPC.