Altitude Acclimatization Research Articles

Effect of ubiquinol on cardiorespiratory fitness during high-altitude acclimatization and de-acclimatization in healthy adults: the Shigatse CARdiorespiratory fitness study design.

Cardiorespiratory function influences exercise capacity and is an important determinant of high-altitude adaptation. Some studies have investigated the characteristics of changes in cardiorespiratory fitness during high-altitude acclimatization. However, studies on changes in cardiorespiratory fitness during high-altitude de-acclimatization are still lacking and have not yet been elucidated. Furthermore, few drugs have been studied to improve cardiorespiratory function during both processes. The Shigatse CARdiorespiratory Fitness (SCARF) study is a single-center, randomized, double-blind, placebo-control clinical trial to explore the effects of ubiquinol on cardiorespiratory fitness during high-altitude acclimatization and de-acclimatization in healthy adults. Participants will be randomly assigned 1:1 to ubiquinol 200 mg daily or a placebo for 14 days before departure until the end of data collection after return in 7 days. Cardiorespiratory fitness is the primary outcome, while acute mountain sickness and high-altitude de-acclimatization symptoms are secondary endpoints. In addition, laboratory measurements, including routine blood tests and serological measurements, will be performed. To the best of our knowledge, the SCARF study will be the first to reveal the changes in the cardiorespiratory fitness characteristics during high-altitude acclimatization and de-acclimatization. Furthermore, the results of this study will contribute to exploring whether ubiquinol supplementation could be beneficial for endurance exercise capacity at different altitudes and help improve adaptation to acute hypoxia and de-acclimatization. Clinical Trial Registration: This study has been registered in the Chinese Clinical Trial Register (www.chictr.org.cn) as ChiCTR2200059900 and ChiCTR2200066328.

Influence of chronic hypoxia on the hypoxic ventilatory response of juvenile and adult rats

Chronic hypoxia (CH) from birth attenuates the acute hypoxic ventilatory response (HVR) in rats and other mammals, but CH is often reported to augment the HVR in adult mammals. To test the hypothesis that this transition – from blunting to augmenting the HVR – occurs in the third or fourth postnatal week in rats, juvenile and adult rats were exposed to normobaric CH (12% O2) for 7 days and the HVR was assessed by whole-body plethysmography. No transition was observed, however, and the acute HVR was reduced by 61 – 85% across all ages studied. The failure to observe an augmented HVR in adult rats could not be explained by the substrain of Sprague Dawley rats used, the duration of the CH exposure, the order in which test gases were presented, the level of hypoxia used for CH and to assess the HVR, or the effects of CH on the metabolic response to hypoxia and the hypercapnic ventilatory response. A literature survey revealed several distinct patterns of ventilatory acclimatization to hypoxia (VAH) in adult rats, with most studies (77%) revealing a decrease or no change in the acute HVR after CH. In conclusion, the effects of CH on respiratory control are qualitatively similar across age groups, at least within the populations of Sprague Dawley rats used in the present study, and there does not appear to be one “typical” pattern for VAH in adult rats.

Effects of Hypobaric Hypoxia on Coagulation in Healthy Subjects Exposed to 3,500 m Altitude.

Kammerer, Tobias, Anna Walzl, Thomas Müller, Philipp Groene, Giulia Roveri, Rachel Turner, Johanna Roche, Hannes Gatterer, Christoph Siebenmann, and Simon T. Schäfer. Effects of hypobaric hypoxia on coagulation in healthy subjects exposed to 3,500 m altitude. High Alt Med Biol. 24:94-103, 2023. Background: Hypoxia is discussed as a trigger for prothrombotic changes both in intensive care and high altitude medicine. This research study aimed to evaluate the effect of isolated hypobaric hypoxia (HH) on coagulation in females in a highly standardized setting. Methods: Twelve healthy female subjects were studied under HH (equivalent to 3,500 m) and normoxia (NX) during two 4-day sojourns, in a strictly controlled crossover design. Nutrition, fluid intake, hormonal status (i.e., menstrual cycle variation), and physical stress were standardized. Functional coagulation and blood lysis were measured by viscoelastometry and compared between HH and NX. In addition, plasma-based coagulation tests (PBCTs), namely prothrombin time, activated partial thromboplastin time, fibrinogen, factor VIII coagulation activity (FVIII:C), von Willebrand factor antigen (vWF:Ag), and von Willebrand factor ristocetin cofactor activity (vWF:RCo) were measured. Results: Neither for Viscoelastic Haemostatic Assays nor for PBCTs significant changes were found for HH compared with NX (all p > 0.05). Specifically, the lysis ability, as well as clotting time, clot formation, clot amplitude, and maximum clot firmness unchanged were similar between HH and NX. This also applied to all other variables. Conclusion: We demonstrate that moderate HH per se has no influence on blood coagulation in healthy females.

The change of attention network functions and physiological adaptation during high-altitude hypoxia and reoxygenation

Previous studies have not reached a definitive conclusion regarding the effect of high-altitude hypoxia and reoxygenation on attention. To clarify the influence of altitude and exposure time on attention and the relations between physiological activity and attention, we conducted a longitudinal study to track attention network functions in 26 college students. The scores on the attention network test and physiological data, including heart rate, percutaneous arterial oxygen saturation (SpO2), blood pressure, and vital capacity in pulmonary function measurement, were collected at five time-points: two weeks before arriving at high altitude (baseline), within 3 days after arriving at high altitude (HA3), 21 days after arriving at high altitude (HA21), 7 days after returning to sea level (POST7) and 30 days after returning to sea level (POST30). The alerting scores at POST30 were significantly higher than those at baseline, HA3 and HA21; the orienting scores at HA3 were lower than those at POST7 and POST30; the executive control scores at POST7 were significantly lower than those at baseline, HA3, HA21, and POST30; and the executive control scores at HA3 were significantly higher than those at POST30. The change in SpO2 during high-altitude acclimatization (from HA3 to HA21) was positively correlated with the orienting score at HA21. Vital capacity changes during acute deacclimatization positively correlated with orienting scores at POST7. Attention network functions at the behavioral level did not decline after acute hypoxia exposure compared with baseline. Attention network functions after returning to sea level were improved compared with those during acute hypoxia; additionally, alerting and executive function scores were improved compared with those at baseline. Thus, the speed of physiological adaptation could facilitate the recovery of orienting function during acclimatization and deacclimatization.

Association Between Ferritin Levels and Altitude-Dependent Cardiorespiratory Fitness in Mountain Guides.

Pühringer, Reinhard, Martina Muckenthaler, and Martin Burtscher. Association between ferritin levels and altitude-dependent cardiorespiratory fitness in mountain guides. High Alt Med Biol. 24:139-143, 2023. Background: Higher ferritin levels may be associated with lower cardiorespiratory fitness (CRF; i.e., maximal oxygen uptake, VO2max) and may represent early markers of cardiovascular risk but may also support high-altitude acclimatization. To evaluate these potential associations, data recordings from a large sample of male mountain guides have been analyzed. Methods: A total of 154 data sets (including anthropometric data, VO2max, blood lipids, hemoglobin, ferritin, and transferrin levels) of regularly physically active and well-acclimatized mountain guides were available for analyses. Participants performed equal incremental cycle ergometer tests to exhaustion at low (600 m) and (∼1 week later) at moderate altitude (2,000 m). Results: Ferritin levels were positively correlated with levels of hemoglobin (r = 0.29, p < 0.01), total cholesterol (r = 0.18, p < 0.05), triglycerides (r = 0.23, p < 0.01), and low-density lipoprotein (r = 0.22, p < 0.01), and negatively with high-density lipoprotein levels (r = -0.16, p < 0.05) and also with baseline (taken at low altitude) VO2max values (r = -0.19, p < 0.05). In contrast, higher ferritin levels were associated with less VO2max decline from low-to-moderate altitude (r = 0.26, p < 0.01). Conclusion: Higher ferritin levels in male mountain guides are weakly associated with lower CRF and higher prevalence of cardiovascular risk factors but with slightly less reduction in VO2max when acutely exposed to moderate altitude. The clinical relevance of these observations needs further investigation.

Changes in DNA methylation patterns during high-altitude acclimatization

High altitude is a physiologically stressful environment, in part due to reduced atmospheric oxygen pressure leading to hypoxemia. While the physiological changes that occur during acclimatization to high altitude are well characterized, it is unknown what role epigenetic gene regulation may play in these processes. Therefore, the objective of this study was to measure global changes in DNA methylation in response to acute high-altitude exposure, as well as changes in key hypoxia-inducible factor (HIF) pathway genes including EPAS1[E1] (HIF-2α) and EGLN1 (PHD2). Previous studies suggest that EPAS1 and EGLN1 may play key roles in high-altitude adaptation by promoting erythropoiesis, angiogenesis, and modulating metabolic pathways. We hypothesized that acute high-altitude exposure would produce global hypomethylation, as well as increased methylation of the EGLN1 promoter region and decreased methylation of the EPAS1 promoter region, resulting in increased expression of HIF-2α and increased HIF-pathway activation. To test this hypothesis, 15 (5 women, 10 men) healthy participants of sea-level ancestry were recruited (age = 25 ± 4.8). DNA was isolated from venous blood samples which were collected during fasting at sea level and over the course of three days of acclimatization to 3800 m elevation at Barcroft Station (Bishop, CA). DNA methylation levels were measured at CpG sites across the genome using the Illumina Infinium MethylationEPIC chip, and local DNA methylation for EPAS1 and EGLN1 was obtained using a high-resolution melt technique. We identified several CpG sites throughout the genome that were differentially methylated during high-altitude exposure. The top gene ontology terms for differentially methylated sites include bone cell development, DNA damage repair pathways related to p53, and myeloid cell development. There were also significant decreases in CpG sites within HIF-pathway genes such as CD44 and FOXP1. Finally, DNA methylation levels within EPAS1 and EGLN1 changed significantly throughout the process of high-altitude acclimatization, with methylation levels increasing in some regions and decreasing in others. In conclusion, high-altitude exposure leads to complex changes in DNA methylation patterns throughout the genome. These changes likely play a key role in acclimatization and adaptation to chronic hypoxia and future studies will explore these mechanisms. This work has implications for understanding the role of epigenetics in diseases associated with hypoxia such as COPD, COVID-19, sleep apnea, and reproductive diseases such as preeclampsia and endometriosis. This work was funded by a UCR Regent's Faculty Fellowship to ECH and by the UCR School of Medicine. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Clinical features and health-threatening conditions of the trek to Capanna Margherita.

Since trips to high altitude have become popular, reports on clinical and environmental characteristics during expeditions to popular destinations are needed. A group of 15 healthy adults was monitored during a trek to Capanna Margherita (4556 m). A hypoxic stress test was applied before the expedition started. Environmental characteristics were acquired with a portable device. Vital signs were compared at low and high altitude, and altitude sickness was diagnosed by the Lake Louise scoring system. Ocular symptoms and intraocular pressure were recorded. Temperature ranged from -3.5 to 31.3 °C and relative humidity from 36 to 95% during the trek. Acute mountain sickness was diagnosed in 40% of participants, more frequently in women, and slightly associated with a greater drop in SpO<inf>2</inf>. Heart rate and blood pressure increased, while peripheral saturation and intraocular pressure decreased, in response to altitude hypoxia. Rapid ascents, as in the most common expedition plans, should be carefully supervised because of the common occurrence of AMS, especially in women. Among organ districts, the eye should deserve more attention in high-altitude medicine. Analyses of environmental conditions, together with predictive methods and early identification of health-threatening conditions, are of great value in supporting further recreational, professional and scientific expeditions to the most intriguing altitude sites.

Microvascular and oxidative stress responses to acute high-altitude exposure in prematurely born adults

Premature birth is associated with endothelial and mitochondrial dysfunction, and chronic oxidative stress, which might impair the physiological responses to acute altitude exposure. We assessed peripheral and oxidative stress responses to acute high-altitude exposure in preterm adults compared to term born controls. Post-occlusive skeletal muscle microvascular reactivity and oxidative capacity from the muscle oxygen consumption recovery rate constant (k) were determined by Near-Infrared Spectroscopy in the vastus lateralis of seventeen preterm and seventeen term born adults. Measurements were performed at sea-level and within 1 h of arrival at high-altitude (3375 m). Plasma markers of pro/antioxidant balance were assessed in both conditions. Upon acute altitude exposure, compared to sea-level, preterm participants exhibited a lower reperfusion rate (7 ± 31% vs. 30 ± 30%, p = 0.046) at microvascular level, but higher k (6 ± 32% vs. −15 ± 21%, p = 0.039), than their term born peers. The altitude-induced increases in plasma advanced oxidation protein products and catalase were higher (35 ± 61% vs. −13 ± 48% and 67 ± 64% vs. 15 ± 61%, p = 0.034 and p = 0.010, respectively) and in xanthine oxidase were lower (29 ± 82% vs. 159 ± 162%, p = 0.030) in preterm compared to term born adults. In conclusion, the blunted microvascular responsiveness, larger increases in oxidative stress and skeletal muscle oxidative capacity may compromise altitude acclimatization in healthy adults born preterm.

Sex-related Differences in Loop Gain during High-Altitude Sleep-disordered Breathing.

Rationale: Central sleep apnea (CSA) is pervasive during sleep at high altitude, disproportionately impacting men and associated with increased peripheral chemosensitivity. Objectives: We aimed to assess whether biological sex affects loop gain (LGn) and CSA severity during sleep over 9-10 days of acclimatization to 3,800 m. We hypothesized that CSA severity would worsen with acclimatization in men but not in women because of greater increases in LGn in men. Methods: Sleep studies were collected from 20 (12 male) healthy participants at low altitude (1,130 m, baseline) and after ascent to (nights 2/3, acute) and residence at high altitude (nights 9/10, prolonged). CSA severity was quantified as the respiratory event index (REI) as a surrogate of the apnea-hypopnea index. LGn, a measure of ventilatory control instability, was quantified using a ventilatory control model fit to nasal flow. Linear mixed models evaluated effects of time at altitude and sex on respiratory event index and LGn. Data are presented as contrast means with 95% confidence intervals. Results: REI was comparable between men and women at acute altitude (4.1 [-9.3, 17.5] events/h; P = 0.54) but significantly greater in men at prolonged altitude (23.7 [10.3, 37.1] events/h; P = 0.0008). Men had greater LGn than did women for acute (0.08 [0.001, 0.15]; P = 0.047) and prolonged (0.17 [0.10, 0.25]; P < 0.0001) altitude. The change in REI per change in LGn was significantly greater in men than in women (107 ± 46 events/h/LGn; P = 0.02). Conclusions: The LGn response to high altitude differed between sexes and contributed to worsening of CSA over time in men but not in women. This sex difference in acclimatization appears to protect females from high altitude-related CSA. Thesedata provide fundamental sex-specific physiological insightinto high-altitude acclimatization in healthy individuals and may help to inform sex differences in sleep-disordered breathing pathogenesis in patients with cardiorespiratory disease.

Identification of key pathways, genes and immune cell infiltration in hypoxia of high-altitude acclimatization via meta-analysis and integrated bioinformatics analysis.

Background: For individuals acutely exposed to high-altitude regions, environmental hypobaric hypoxia induces several physiological or pathological responses, especially immune dysfunction. Therefore, hypoxia is a potentially life-threatening factor, which has closely related to high-altitude acclimatization. However, its specific molecular mechanism is still unclear. Methods: The four expression profiles about hypoxia and high altitude were downloaded from the Gene Expression Omnibus database in this study. Meta-analysis of GEO datasets was performed by NetworkAnalyst online tool. Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene ontology (GO) enrichment analysis, and visualization were performed using R (version 4.1.3) software, respectively. The CIBERSORT analysis was conducted on GSE46480 to examine immune cell infiltration. In addition, we experimentally verified the bioinformatics analysis with qRT-PCR. Results: The meta-analysis identified 358 differentially expressed genes (DEGs), with 209 upregulated and 149 downregulated. DEGs were mostly enriched in biological processes and pathways associated with hypoxia acclimatization at high altitudes, according to both GO and KEGG enrichment analyses. ERH, VBP1, BINP3L, TOMM5, PSMA4, and POLR2K were identified by taking intersections of the DEGs between meta-analysis and GSE46480 and verified by qRT-PCR experiments, which were inextricably linked to hypoxia. Immune infiltration analysis showed significant differences in immune cells between samples at sea level and high altitudes. Conclusion: Identifying the DEGs and pathways will improve our understanding of immune function during high-altitude hypoxia at a molecular level. Targeting hypoxia-sensitive pathways in immune cells is interesting in treating high-altitude sickness. This study provides support for further research on high-altitude acclimatization.

Under the Southern Cross and Ranrapalca in Cordillera Blanca, Peru.

After completing an alpine rescue exercise in June 2022, participants of the Diploma in Mountain Medicine of the Andes descended the slopes of the Ishinca Glacier in the Cordillera Blanca, Peru. In the background, the massive Mount Ranrapalca (6162 m) is guarded from the sky by the Southern Cross. Although the Southern Cross has held importance in many cultures, it is a potent symbol of the Andean culture. The staggered Andean cross of the Incas, “Chakana,” represents the Southern Cross.1 Here, the 3 worlds of the Inca belief system coexist: Uqhu Pacha (underworld), represented by a snake; Kay Pacha (middle world), represented by the puma; and finally, Hanan Pacha (upperworld), represented by the condor.

Arterial Blood Gases in Normal Subjects at 2240 Meters Above Sea Level: Impact of Age, Gender, and Body Mass Index.

The values of arterial blood gases (ABG) change with altitude above sea level; empirical verification is essential because ventilatory acclimatization varies with ethnicity and a population's adaptation. The aim of the study was to describe ABG in a healthy population residing at 2,240 meters above sea level, to identify the mean level of alveolar ventilation (PaCO2), and to know whether a progressive increase in PaCO2 occurs with age and the impact of increasing body mass index (BMI). We conducted a cross-sectional study in a referral center for respiratory diseases in Mexico City. Associations among variables with correlation coefficient and regression models of PaO2, SaO2, and P(A-a)O2 as dependent variables as a function of age, BMI, minute ventilation, or breathing frequency were explored. Two hundred and seventeen healthy subjects were evaluated with a mean age of 40 ± 15 years, mean of the PaO2 was 71 ± 6 mmHg, SaO2 94% ± 1.6%, PaCO2 30.2 ± 3.4 mmHg, HCO3 20 ± 2 mmol/L, BE-2.9 ± 1.9 mmol/L, and the value of pH was 7.43 ± 0.02. In a linear regression, the main results were PaO2 = 77.5-0.16*age (p < 0.0001) and with aging P(A-a)O2 tended to increase 0.12 mmHg/year. PaCO2 in women increased with age by 0.075 mmHg/year (p = 0.0012, PaCO2 =26.3 + 0.075*age). SaO2 and PaO2 decreased significantly in women with higher BMI 0.14% and 0.52 mmHg per kg/m2, (p = 0.004 and 0.002 respectively). Mean PaCO2 was 30.7 mmHg, implying a mean alveolar ventilation of around 30% above that at sea level.

A monocarboxylate transporter-dependent mechanism confers resistance to exercise-induced fatigue in a high-altitude hypoxic environment

The body is more prone to fatigue in a high-altitude hypoxic environment, in which fatigue occurs in both peripheral muscles and the central nervous system (CNS). The key factor determining the latter is the imbalance in brain energy metabolism. During strenuous exercise, lactate released from astrocytes is taken up by neurons via monocarboxylate transporters (MCTs) as a substrate for energy metabolism. The present study investigated the correlations among the adaptability to exercise-induced fatigue, brain lactate metabolism and neuronal hypoxia injury in a high-altitude hypoxic environment. Rats were subjected to exhaustive incremental load treadmill exercise under either normal pressure and normoxic conditions or simulated high-altitude, low-pressure and hypoxic conditions, with subsequent evaluation of the average exhaustive time as well as the expression of MCT2 and MCT4 in the cerebral motor cortex, the average neuronal density in the hippocampus, and the brain lactate content. The results illustrate that the average exhaustive time, neuronal density, MCT expression and brain lactate content were positively correlated with the altitude acclimatization time. These findings demonstrate that an MCT-dependent mechanism is involved in the adaptability of the body to central fatigue and provide a potential basis for medical intervention for exercise-induced fatigue in a high-altitude hypoxic environment.

Monocarboxylate transporter-dependent mechanism is involved in the adaptability of the body to exercise-induced fatigue under high-altitude hypoxia environment

Under high-altitude hypoxia environment, the body is more prone to fatigue, which occurs in both peripheral muscles and the central nervous system (CNS). The key factor determining the latter is the imbalance of brain energy metabolism, which makes it difficult to maintain the central nervous system to send peripheral nerve impulse continuously. During strenuous exercise, lactate released from astrocytes is taken up by neurons stored for energy to maintain synaptic transmission, a process mediated by monocarboxylate transporters (MCTs) in CNS. The present study investigated the correlation among the adaptability to exercise-induced fatigue, brain lactate metabolism and neuronal hypoxia injury under high-altitude hypoxia environment. Rats were subjected to exhaustive incremental load treadmill exercise under either normal pressure and normoxic conditions or simulated high-altitude low pressure and hypoxic conditions, with subsequent evaluation of the average exhaustive time as well as the expression of monocarboxylate transporters 2 (MCT2), MCT4, the average neuronal density in the cerebral motor cortex, and the lactate content in rat brain. At the early stage of simulated high-altitude environment, the average exhaustive time and neuronal density of rats decreased rapidly, then gradually recovered to some extent with the extension of altitude acclimatization time. The expression of MCT2, MCT4 and the lactate content in rat brain also increased gradually with the extension of altitude acclimatization time. After the application of lactate transport inhibitor, the recovery of exercise capacity of rats after altitude acclimatization was quickly blocked, and the neuronal injury in the cerebral motor cortex of rats was also significantly aggravated. These findings demonstrate that MCT-dependent mechanism is involved in the adaptability of the body to central fatigue, and provide a potential basis for medical intervention for exercise-induced fatigue under high-altitude hypoxia environment.

Effects of age on hypoxic tolerance in women

Effects of age on hypoxic tolerance in women

Nutrition and Hydration for High-Altitude Alpinism: A Narrative Review

This report aims to summarise the scientific knowledge around hydration, nutrition, and metabolism at high altitudes and to transfer it into the practical context of extreme altitude alpinism, which, as far as we know, has never been considered before in the literature. Maintaining energy balance during alpine expeditions is difficult for several reasons and requires a deep understanding of human physiology and the biological basis for altitude acclimation. However, in these harsh conditions it is difficult to reconcile our current scientific knowledge in sports nutrition or even for mountaineering to high-altitude alpinism: extreme hypoxia, cold, and the logistical difficulties intrinsic to these kinds of expeditions are not considered in the current literature. Requirements for the different stages of an expedition vary dramatically with increasing altitude, so recommendations must differentiate whether the alpinist is at base camp, at high-altitude camps, or attempting the summit. This paper highlights nutritional recommendations regarding prioritising carbohydrates as a source of energy and trying to maintain a protein balance with a practical contextualisation in the extreme altitude environment in the different stages of an alpine expedition. More research is needed regarding specific macro and micronutrient requirements as well as the adequacy of nutritional supplementations at high altitudes.

Adrenergic control of skeletal muscle blood flow during chronic hypoxia in healthy males.

Sympathetic transduction is reduced following chronic high-altitude (HA) exposure; however, vascular α-adrenergic signaling, the primary mechanism mediating sympathetic vasoconstriction at sea level (SL), has not been examined at HA. In nine male lowlanders, we measured forearm blood flow (Doppler ultrasound) and calculated changes in vascular conductance (ΔFVC) during 1) incremental intra-arterial infusion of phenylephrine to assess α1-adrenergic receptor responsiveness and 2) combined intra-arterial infusion of β-adrenergic and α-adrenergic antagonists propranolol and phentolamine (α-β-blockade) to assess adrenergic vascular restraint at rest and during exercise-induced sympathoexcitation (cycling; 60% peak power). Experiments were performed near SL (344 m) and after 3 wk at HA (4,383 m). HA abolished the vasoconstrictor response to low-dose phenylephrine (ΔFVC: SL: -34 ± 15%, vs. HA; +3 ± 18%; P < 0.0001) and markedly attenuated the response to medium (ΔFVC: SL: -45 ± 18% vs. HA: -28 ± 11%; P = 0.009) and high (ΔFVC: SL: -47 ± 20%, vs. HA: -35 ± 20%; P = 0.041) doses. Blockade of β-adrenergic receptors alone had no effect on resting FVC (P = 0.500) and combined α-β-blockade induced a similar vasodilatory response at SL and HA (P = 0.580). Forearm vasoconstriction during cycling was not different at SL and HA (P = 0.999). Interestingly, cycling-induced forearm vasoconstriction was attenuated by α-β-blockade at SL (ΔFVC: Control: -27 ± 128 vs. α-β-blockade: +19 ± 23%; P = 0.0004), but unaffected at HA (ΔFVC: Control: -20 ± 22 vs. α-β-blockade: -23 ± 11%; P = 0.999). Our results indicate that in healthy males, altitude acclimatization attenuates α1-adrenergic receptor responsiveness; however, resting α-adrenergic restraint remains intact, due to concurrent resting sympathoexcitation. Furthermore, forearm vasoconstrictor responses to cycling are preserved, although the contribution of adrenergic receptors is diminished, indicating a reliance on alternative vasoconstrictor mechanisms.

Molecular Mechanisms of High-Altitude Acclimatization.

High-altitude illnesses (HAIs) result from acute exposure to high altitude/hypoxia. Numerous molecular mechanisms affect appropriate acclimatization to hypobaric and/or normobaric hypoxia and curtail the development of HAIs. The understanding of these mechanisms is essential to optimize hypoxic acclimatization for efficient prophylaxis and treatment of HAIs. This review aims to link outcomes of molecular mechanisms to either adverse effects of acute high-altitude/hypoxia exposure or the developing tolerance with acclimatization. After summarizing systemic physiological responses to acute high-altitude exposure, the associated acclimatization, and the epidemiology and pathophysiology of various HAIs, the article focuses on molecular adjustments and maladjustments during acute exposure and acclimatization to high altitude/hypoxia. Pivotal modifying mechanisms include molecular responses orchestrated by transcription factors, most notably hypoxia inducible factors, and reciprocal effects on mitochondrial functions and REDOX homeostasis. In addition, discussed are genetic factors and the resultant proteomic profiles determining these hypoxia-modifying mechanisms culminating in successful high-altitude acclimatization. Lastly, the article discusses practical considerations related to the molecular aspects of acclimatization and altitude training strategies.

A bibliometric analysis of the studies in high-altitude induced sleep disturbances and cognitive impairment research.

Background: The two main symptoms at high altitude, sleep abnormalities and cognitive impairments, interact with each other. These two dysfunctions are also closely related to systemic multisystem diseases, including cerebrovascular diseases, psychiatric disorders, and immune regulatory diseases. Purpose: To systematically analyze and visualize research on sleep disturbances and cognitive impairment at high altitudes using a bibliometrics method, and to determine future research directions by analyzing research trends and the latest hotspots. Methods: Publications from 1990 to 2022 on sleep disturbances and cognitive impairment at high altitudes were retrieved from the Web of Science. Using the R Bibliometrix software and Microsoft Excel, all data were examined statistically and qualitatively. For network visualization, the data were later exported into VOSviewer 1.6.17 and CiteSpace 6.1.R6. Results: A total of 487 articles in this area were published from 1990 to 2022. In this period, there was an overall increase in the number of publications. The United States has shown considerable importance in this sector. Bloch Konrad E was the most prolific and valuable author. The most prolific journal was High Altitude Medicine & Biology, and it has been the first choice for publishing in this field in recent years. Analysis of keyword co-occurrences suggested that research interest in the clinical manifestations of sleep disturbances and cognitive impairment caused by altitude hypoxia was mainly focused on "acute mountain-sickness," "insomnia," "apnea syndrome," "depression," "anxiety," "Cheyne-strokes respiration," and "pulmonary hypertension." The mechanisms of disease development related to "oxidative stress," "inflammation," "hippocampus," "prefrontal cortex," "neurodegeneration," and "spatial memory" in the brain have been the focus of recent research. According to burst detection analysis, "mood" and "memory impairment," as terms with high strength, are expected to remain hot topics in the coming years. High-altitude-induced pulmonary hypertension is also in the emerging stage of research, and the treatments will continue to receive attention in the future. Conclusion: More attention is being focused on sleep disturbances and cognitive impairment at high altitudes. This work will serve as a useful reference for the clinical development of treatments for sleep disturbances and cognitive impairment induced by hypobaric hypoxia at high altitudes.

The use of the UCLan Mountain Medicine and other Masters programmes as a recruitment tool for healthcare organisations with difficulties in recruitment and retention.

A variety of incentives are used to stimulate recruitment to remote and rural locations. In this presentation, we share experiences at the University of Central Lancashire of forming partnerships with National Health Service (NHS) organisations to offer investment in careers as a recruitment and retention tool. Qualitative structured interviews. NHS organisations priorities were to find cost-effective and successful strategies to recruit and retain workers. Many had tried financial incentives, including 'golden handshakes' and 'golden handcuffs' but found them ineffective or unaffordable. Prospective employee priorities were multifactorial, including a desire for flexibility, manageable workload and the ability to develop their personal and career interests. Whilst rates of pay were important, one-off lump sum payments were viewed as having lower value. This partnership approach has helped us develop MSc programmes that fit with the needs of their services and innovatively support their recruitment aims. We have also given voice to the needs of our learners, for example by encouraging job planning approaches that facilitate the prolonged blocks of leave required for acclimatisation of practitioners of Mountain Medicine to travel to high altitude. When explored, advertised one-off lump sum payments amounts were perceived as being misleading due to tax deductions, diminishing their utility as a 'feel good' factor in retention. Conversely, gradual investment over time, using academic study as an enabler for flexible job planning combined with a feeling that their employer supported some of their drivers and values contributed to a greater sense of commitment by employees.