Search

Introduction: This study aimed to investigate the effects of normobaric hypoxia (NH) and hypobaric hypoxia (HH) on associative memory performance for emotionally valenced stimuli., Methods: Two experiments were conducted. In Study 1, n = 18 undergraduates performed an associative memory task under three NH conditions (FiO 2 = 20.9 %, 15.1 %, 13.6 %) using a tent with a hypoxic generator. In Study 2, n = 20 participants were assessed in a field study at various altitudes on the Himalayan mountains, including the Pyramid Laboratory (5000 m above sea level), using functional Near-Infrared Spectroscopy (fNIRS) and behavioral assessments., Results: Study 1 revealed no significant differences in recognition accuracy across NH conditions. However, Study 2 showed a complex relationship between altitude and memory for emotionally valenced stimuli. At lower altitudes, participants more accurately recognized emotional stimuli compared to neutral ones, a trend that reversed at higher altitudes. Brain oxygenation varied with altitude, indicating adaptive cognitive processing, as revealed by fNIRS measurements., Conclusions: These findings suggest that hypoxia affects associative memory and emotional processing in an altitude-dependent manner, highlighting adaptive cognitive mechanisms. Understanding the effects of hypobaric hypoxia on cognition and memory can help develop strategies to mitigate its impact in high-altitude and hypoxic environments., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Humans exposed to altitude hypoxia experience dysfunctions of the urinary system. As a non-invasive, easily manageable and informative biological sample, urine represents a relevant matrix for detecting clinical impairments of urinary system, as well as alterations of other systems and extracellular vesicles (EVs) biology during high-altitude expeditions. Nevertheless, gaps exist in the comprehensive assessment of dysfunction, molecular burden and EVs biology due to high-altitude acute exposure. This study aimed to find a biophysical and biochemical signature of urinary EVs for hypoxia-induced changes in urinary function, putatively accompanied by an oxinflammatory burden. Urine samples of 15 participants were sampled at low and high-altitude during an Alpine project (7 women and 8 men, aged 24-to-63 years and with BMI 17.93-to-30.76 kg/m 2 ) and analysed for: creatinin and albumin, lipid peroxidation, IL6, NO derivatives; atomic force microscopy and Raman spectroscopy were carried out after urinary EVs were isolated through sucrose-gradient ultracentrifugation. Albumin-to-creatinin ratio increased at high altitude, as did IL6 and 8-isoprostane. AFM showed a globular and flattened shape of EVs, although several samples were characterized by a lot of contaminants and EVs lost their prototypal spherical shape; EVs comprehensively maintained their morphology at high altitude. Raman spectroscopy revealed some typical phospholipidic-like pattern, often masked by contaminants of spectra that most often refer to high-altitude samples. Collectively, short-term exposure to altitude hypoxia increased renal concentrating ability, produced non-pathological impairment or renal function, and triggered an oxyinflammatory burden with heterogeneous response of NO system. The combination of AFM and Raman spectroscopy revealed that EVs collected at high altitude more likely are fused together and incorporated into a sediment matrix, and contain contaminants peaks that make the purification process less efficient. The combination of analytical procedures as in the present study offers novel possibilities to detect the biological and clinical effects of high altitude on renal system., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Exposure to high altitude might cause the body to adapt with negative energy and fluid balance that compromise body composition and physical performance. In this field study involving 12 healthy adults, sex-balanced, and aged 29 ± 4 years with a body mass index of 21.6 ± 1.8 kg/m 2 , we investigated the effects of a 4-day trekking up to 4556 m a.s.l. on Monte Rosa (Alps, Italy). The food intake was recorded using food diaries and nutrient averages were calculated. The bio-impedance analysis was performed at low and high altitudes, and a wearable biosensor (Swemax) was used to track hydro-saline losses in two participants. Daily total energy intake was 3348 ± 386 kcal for males and 2804 ± 415 kcal for females (13%-14% protein, 35% fat, 44%-46% carbohydrates). Although there was a significant body weight loss (65.0 ± 9.3 vs. 64.2 ± 9.10 kg, p  < 0.001, d  = 1.398), no significant changes in body composition parameter were found but a trend in the increase of the bioelectrical phase angle in males ( p  = 0.059, d = -0.991). Body water percentage significantly changed ( p  = 0.026, η 2 p   = 0.440), but the absolute water did not, suggesting that the weight loss was not due to water loss. Salivary and urinary osmolality did not change. A reduction in sweat rate at higher altitudes was observed in both participants. Interestingly, salivary leptin increased ( p  = 0.014, η  = 0.403). Therefore, the 4-day trekking at altitude of hypoxia exposure induced changes in satiety and appetite hormones. High altitude expeditions require more specific nutritional guidance, and using multiplex analysis could help in monitoring fluid balance and body composition.2 p   = 0.510), and salivary ghrelin decreased ( p  = 0.036, η 2 p  = 0.403). Therefore, the 4-day trekking at altitude of hypoxia exposure induced changes in satiety and appetite hormones. High altitude expeditions require more specific nutritional guidance, and using multiplex analysis could help in monitoring fluid balance and body composition., Competing Interests: Matteo Beccatelli, Pierluigi Lodi Rizzini, Davide Seletti, Rocco Mecca, and Tommaso Beccatelli were employee or collaborators of the company Biometrica S.r.l., Parma, Italy (which provided the device SWEMAX and the technical assistance) while engaged in the research project. The other authors declare there are no competing interests.

This study aimed to evaluate changes in lung function assessed by spirometry and blood gas content in healthy high-altitude sojourners during a trek in the Himalayas. A group of 19 Italian adults (11 males and 8 females, mean age 43 ± 15 years, and BMI 24.2 ± 3.7 kg/m 2 ) were evaluated as part of a Mount Everest expedition in Nepal. Spirometry and arterial blood gas content were evaluated at baseline in Kathmandu (≈1400 m), at the Pyramid Laboratory - Observatory (peak altitude of ≈5000 m), and on return to Kathmandu 2-3 days after arrival at each site. All participants took 250 mg of acetazolamide per os once daily during the ascent. We found that arterial hemoglobin saturation, O 2 and CO 2 partial pressures, and the bicarbonate level all decreased (in all cases, p < 0.001 with R 2 =0.70-0.90), while pHa was maintained stable at the peak altitude. Forced vital capacity (FVC) remained stable, while forced expiratory volume in 1 s (FEV1) decreased (p = 0.010, n 2 p =0.228), resulting in a lower FEV1/FVC ratio (p < 0.001, n 2 partial pressure at the peak altitude (p = 0.004, R p =0.39). Finger pulse oximetry overestimated peripheral saturation relative to arterial saturation. We conclude that high-altitude hypoxia alters the respiratory function and the oxygen saturation of the arterial blood hemoglobin. Additionally, air rarefaction and temperature reduction, favoring hypoxic bronchoconstriction, could affect respiration. Pulse oximetry seems not enough to assist medical decisions at high altitudes.2 partial pressure at the peak altitude (p = 0.004, R 2 =0.39). Finger pulse oximetry overestimated peripheral saturation relative to arterial saturation. We conclude that high-altitude hypoxia alters the respiratory function and the oxygen saturation of the arterial blood hemoglobin. Additionally, air rarefaction and temperature reduction, favoring hypoxic bronchoconstriction, could affect respiration. Pulse oximetry seems not enough to assist medical decisions at high altitudes., Competing Interests: Conflicts of Interest The authors declare no conflicts of interest. No author has any fiduciary relationships or duties to the sponsors., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Many authors described negative but reversible effects of high-altitude hypoxic exposure on animal and human fertility in terms of sperm concentration, function, and biochemical alterations. The aim of this study was to evaluate the acute and chronic effects of high-altitude exposure on classical sperm parameters, redox status, and membrane composition in a group of travellers. Five healthy Italian males, all lowlanders not accustomed to the altitude, were evaluated after 19 days-trekking through low, moderate, and high altitudes in the Himalayas. Sperm samples were collected before (Pre), 10 days after (Post), and 70 days after the end of the expedition (Follow-up). Sperm concentration, cholesterol and oxysterol membrane content, and redox status were measured. Hypoxic trek led to a significant reduction in sperm concentration (p < 0.001, η2p = 0.91), with a reduction from Pre to Post (71.33 ± 38.81 to 60.65 ± 34.63 × 106/mL) and a further reduction at Follow-up (to 37.13 ± 39.17 × 106/mL). The seminal volume was significantly affected by the hypoxic trek (p = 0.001, η2p = 0.75) with a significant reduction from Pre to Post (2.86 ± 0.75 to 1.68 ± 0.49 mL) and with partial recovery at Follow-up (to 2.46 ± 0.45 mL). Moreover, subjects had an increase in ROS production (+86%), and a decrease in antioxidant capacity (−37%) in the Post period with partial recovery at Follow-up. These results integrated the hormonal response on thyroid function, hypothalamus−pituitary−gonadal axis, and the prolactin/cortisol pathways previously reported. An uncontrolled ROS production, rather than a compromised antioxidant activity, was likely the cause of impaired sperm quality. The reduction in fertility status observed in this study may lie in an evolutionary Darwinian explanation, i.e., limiting reproduction due to the “adaptive disadvantage” offered by the combined stressors of high-altitude hypoxia and daily physical exercise.

Altitude hypoxia induces changes in iron homeostasis with serum ferritin (sFER) response being recently linked to erythropoiesis. The main aim of this study was to investigate sFER and Vitamin D (Vit D) response to hypobaric hypoxia, taking into account factors including nutrition and ethnic origin. As part of a "Kanchenjunga Exploration & Physiology" project, 6 Italian trekkers and 6 Nepalese porters took part in a 19-days long altitude trek in the Himalayas self-recording daily food consumption. Blood samples were collected and analyzed before and after the trek for sFER and Vit D. A web-based system calculated the dietary intake, generating reports that were used for later statistical analyses. sFER decreased after the trek (on average by 26% p  = 0.013, partial η 2  = 0.479) in both groups, whereas Vit D did not change in both groups. Nepalese tended to have lower sFER, but this difference was reduced when corrected for the dietary intake. Mean Cell Volume (MCV) and Hematocrit (HCT), in respect to baseline, remained higher 10 days after the trek (respectively, 87.37-88.85 fL with p  = 0.044, and 43.05-44.63% with p  = 0.065) in Italian trekkers. The observed reduction of sFER levels was related to altitude per se as inflammation or anemia were medically excluded. sFER, therefore, may act as a primary factor in the examination of hypobaric hypoxia in field studies. The results of this study open a new door into the mechanisms of iron homeostasis in specific tissues related to hypoxia adaptations, taking into account dietary intake and ethnic origin.

Purpose: The Wingate anaerobic test measures the maximum anaerobic capacity of the lower limbs. The energy sources of Wingate test are dominated by anaerobic metabolism (~ 80%). Chronic high altitude exposure induces adaptations on skeletal muscle function and metabolism. Therefore, the study aim was to investigate possible changes in the energy system contribution to Wingate test before and after a high-altitude sojourn., Methods: Seven male climbers performed a Wingate test before and after a 43-day expedition in the Himalaya (23 days above 5.000 m). Mechanical parameters included: peak power (PP), average power (AP), minimum power (MP) and fatigue index (FI). The metabolic equivalents were calculated as aerobic contribution from O 2 uptake during the 30-s exercise phase (W VO2 ), lactic and alactic anaerobic energy sources were determined from net lactate production (W La ) and the fast component of the kinetics of post-exercise oxygen uptake (W PCr ), respectively. The total metabolic work (W TOT ) was calculated as the sum of the three energy sources., Results: PP and AP decreased from 7.3 ± 1.1 to 6.7 ± 1.1 W/kg and from 5.9 ± 0.7 to 5.4 ± 0.8 W/kg, respectively, while FI was unchanged. W TOT declined from 103.9 ± 28.7 to 83.8 ± 17.8 kJ. Relative aerobic contribution remained unchanged (19.9 ± 4.8% vs 18.3 ± 2.3%), while anaerobic lactic and alactic contributions decreased from 48.3 ± 11.7 to 43.1 ± 8.9% and increased from 31.8 ± 14.5 to 38.6 ± 7.4%, respectively., Conclusion: Chronic high altitude exposure induced a reduction in both mechanical and metabolic parameters of Wingate test. The anaerobic alactic relative contribution increased while the anaerobic lactic decreased, leaving unaffected the overall relative anaerobic contribution to Wingate test.

Exposure to high altitude is one of the most widely used models to study the adaptive response to hypoxia in humans. However, little is known about the related effects on micturition. The present study addresses the adaptive urinary responses in four healthy adult lowlanders, comparing urodynamic indexes at Kathmandu [1,450 m above sea level (a.s.l.); K 1450 ] and during a sojourn in Namche Bazar (3,500 m a.s.l.; NB 3500 ). The urodynamic testing consisted of cistomanometry and bladder pressure/flow measurements. Anthropometrics, electrocardiographic, and peripheral capillary oxygen saturation data were also collected. The main findings consisted of significant reductions in bladder power at maximum urine flow by ~30%, bladder contractility index by 13%, and infused volume both at first (by 57%) and urgency sensation (by 14%) to urinate, indicating a reduced cystometric capacity, at NB 3500 . In addition to the urinary changes, we found that oxygen saturation, body mass index, body surface area, and median RR time were all significantly reduced at altitude. We submit that the hypoxia-related parasympathetic inhibition could be the underlying mechanism of both urodynamic and heart rate adaptive responses to high-altitude exposure. Moreover, increased diuresis and faster bladder filling at altitude may trigger the anticipation of being able to void, a common cause of urgency. We believe that the present pilot study represents an original approach to the study of urinary physiology at altitude.

Long-term exposure to high altitude causes adaptive changes in several blood biochemical markers along with a marked body mass reduction involving both the lean and fat components. The aim of this study was to evaluate the impact of extended physical strain, due to extensive trekking at high altitude, on body composition, selected biomarkers in the blood, and the protective role of a high-protein diet in muscle dysfunction. We found that physical strain at high altitude caused a significant reduction in body mass and body fat, with a concomitant increase in the cross-sectional area of thigh muscles and an unchanged total lean body mass. Further, we found reductions in plasma leptin and homocysteine, while myoglobin, insulin, and C-reactive protein significantly increased. Creatine kinase, lactate dehydrogenase, and leptin normalized per body fat were unchanged. These findings demonstrate that high-altitude hypoxia, involving extended physical effort, has an impact on muscle function and body composition, facilitating sarcopenia and affecting body mass and fat distribution. It also activates pro-inflammatory metabolic pathways in response to muscular distress. These changes can be mitigated by a provision of a high-protein diet.

Altitude hypoxia is often associated with impairment of human reproduction. In this study, hormones and macrophage migration inhibitory factor (MIF, a proinflammatory cytokine with key roles in human reproduction) were determined in seven regularly menstruating, lowlander native women living at sea level participating in 14 days of trekking at moderate and high altitude. Blood and saliva samples were collected from each subject at high altitude (5050 m a.s.l. [above sea level]), and at sea level before and after the expedition. Testosterone level was lowered by high altitude and was restored after the end of the expedition, while progesterone decreased significantly in all participants at the end of the expedition, although most of the participants were in the luteal phase. The salivary concentration of MIF decreased greatly at altitude, but its levels were completely restored after the return to sea level. Our findings showed high sensitivity and rapid changes in the determined parameters in response to the high-altitude hypoxic environment, particularly MIF., (© 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.)

Purpose: We investigated the effects of moderate-intensity training at low and high altitude on VO2 and QaO2 kinetics and on myosin heavy-chain expression (MyHC) in seven women (36.3 yy ± 7.1; 65.8 kg ± 11.7; 165 cm ± 8) who participated in two 12- to 14-day trekking expeditions at low (598 m) and high altitude (4132 m) separated by 4 months of recovery., Methods: Breath-by-breath VO2 and beat-by-beat QaO2 at the onset of moderate-intensity cycling exercise and energy cost of walking (Cw) were assessed before and after trekking. MyHC expression of vastus lateralis was evaluated before and after low-altitude and after high-altitude trekking; muscle fiber high-resolution respirography was performed at the beginning of the study and after high-altitude trekking., Results: Mean response time of VO2 kinetics was faster (P = 0.002 and P = 0.001) and oxygen deficit was smaller (P = 0.001 and P = 0.0004) after low- and high-altitude trekking, whereas ˙ QaO2 kinetics and Cw did not change. Percentages of slow and fast isoforms of MyHC and mitochondrial mass were not affected by low- and high-altitude training. After training altitude, muscle fiber ADP-stimulated mitochondrial respiration was decreased as compared with the control condition (P = 0.016), whereas leak respiration was increased (P = 0.031), leading to a significant increase in the respiratory control ratio (P = 0.016)., Conclusions: Although training did not significantly modify muscle phenotype, it induced beneficial adaptations of the oxygen transport-utilization systems witnessed by faster VO2 kinetics at exercise onset.

The aim of this study was to investigate the effects of the extreme environment of high altitude hypoxia on olfactory threshold. The study was conducted before, during, and after a scientific expedition to Mera Peak (5,800 m). The n-butanol test was used for the assessment of the magnitude of the olfactory threshold. The finding was that the olfactory threshold dramatically increased at high altitude. We conclude that there is a physiological adaptation of olfaction due to altitude-hypoxia.

The study investigated the effect of prolonged hypoxia on central [i.e., cardiovascular oxygen delivery (Q(a)O(2))] and peripheral (i.e., O(2) utilization) determinants of oxidative metabolism response during exercise in humans. To this aim, seven male mountaineers were examined before and immediately after the Himalayan Expedition Interamnia 8000-Manaslu 2008, lasting 43 days, among which, 23 days were above 5,000 m. The subjects showed a decrease in body weight (P < 0.05) and of power output during a Wingate Anaerobic test (P < 0.05) and an increase of thigh cross-sectional area (P < 0.05). Absolute maximal O(2) uptake (VO(2max)) did not change. The mean response time of VO(2) kinetics at the onset of step submaximal cycling exercise was reduced significantly from 53.8 s ± 10.9 to 39.8 s ± 10.9 (P < 0.05), whereas that of Q(a)O(2) was not. Analysis of single fibers dissected from vastus lateralis biopsies revealed that the expression of slow isoforms of both heavy and light myosin subunits increased, whereas that of fast isoforms decreased. Unloaded shortening velocity of fibers was decreased significantly. In summary, independent findings converge in indicating that adaptation to chronic hypoxia brings about a fast-to-slow transition of muscle fibers, resulting in a faster activation of the mitochondrial oxidative metabolism. These results indicate that a prolonged and active sojourn in hypoxia may induce muscular ultrastructural and functional changes similar to those observed after aerobic training.

Objective: To explore the effect of physical exercise at high altitudes (HA) on male reproductive system., Design: Prospective study., Setting: Andrology Clinic, University of L'Aquila, Italy., Patient(s): Seven male mountaineers involved in an expedition at 5,900 m., Intervention(s): Semen analysis, sperm DNA fragmentation with flow cytometry, and reproductive hormone levels., Main Outcome Measure(s): Hormone levels were evaluated at sea level (SL) at baseline (SL-pre), after 22 days of exercise at HA (intermediate), and after 10 days upon reaching SL (SL-post). Sperm parameters, percentage of sperm with fragmented DNA, and body composition measures were evaluated at SL-pre and at SL-post., Result(s): A reduction of sperm concentration, of body mass index (BMI), of waist circumference, and of percentage of body fat was observed at SL-post compared with SL-pre values. Increased levels of FSH and PRL were observed at the intermediate point, and normalized at SL-post, whereas T was higher at SL-post compared with SL-pre levels., Conclusion(s): Physical exercise at HA is associated with a testicular dysfunction leading to a reduced sperm concentration probably through an altered spermiation. The improved body composition after physical exercise might explain the higher T levels observed after the expedition., (Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Depending on the absolute altitude and the duration of exposure, a high altitude environment induces various cellular effects that are strictly related to changes in oxidative balance. In this study, we used in vitro isolated peripheral blood lymphocytes as biosensors to test the effect of hypobaric hypoxia on seven climbers by measuring the functional activity of these cells. Our data revealed that a 21-day exposure to high altitude (5000 m) (1) increased intracellular Ca(2+) concentration, (2) caused a significant decrease in mitochondrial membrane potential, and (3) despite possible transient increases in intracellular levels of reactive oxygen species, did not significantly change the antioxidant and/or oxidative damage-related status in lymphocytes and serum, assessed by measuring Trolox-equivalent antioxidant capacity, glutathione peroxidase activity, vitamin levels, and oxidatively modified proteins and lipids. Overall, these results suggest that high altitude might cause an impairment in adaptive antioxidant responses. This, in turn, could increase the risk of oxidative-stress-induced cellular damage. In addition, this study corroborates the use of peripheral blood lymphocytes as an easily handled model for monitoring adaptive response to environmental challenge.

Aim: To evaluate the effect of chronic hypoxia on human spermatogenic parameters and their recovery time., Methods: Seminological parameters of six male healthy mountain trekkers were evaluated in normoxia at sea level. After 26 days exposure to altitude (ranging from 2 000 m to 5 600 m, Karakorum Expedition) the same parameters were again evaluated after returning to sea level. These parameters were once again evaluated after 1 month and then again after 6 months., Results: Sperm count was found to be lower immediately after returning to sea level (P = 0.0004) and again after a month (P = 0.0008). Normal levels were reached after 6 months. Spermatic motility (%) shows no reduction immediately after returning to sea level (P = 0.0583), whereas after 1 month this reduction was significant (P = 0.0066). After 6 months there was a recovery to pre-hypoxic exposure values. Abnormal or immature spermatozoa (%) increased immediately after returning to sea level (P = 0.0067) and then again after 1 month (P = 0.0004). After 6 months there was a complete recovery to initial values. The total number of motile sperm in the ejaculate was found to be lower immediately after returning to sea level (P = 0.0024) and then again after 1 month (P = 0.0021). After 6 months there was a recovery to pre-hypoxic exposure values., Conclusion: Chronic hypoxia induces a state of oligospermia and the normalization of such seminological parameters at the restoration of previous normoxic conditions after 6 months indicate the influence of oxygen supply in physiological mechanisms of spermatogenesis and male fertility.

Chronic hypoxia is related to many pathological conditions: aging, heart and respiratory failure, sleep apneas, smoke, chronic obstructive pulmonary disease (COPD), diabetes, hypertension and arteriosclerosis, all characterized by reductions of sleep-related erections (SREs) and by erectile dysfunction (ED). Sleep-related erections occur naturally during rapid eye movement (REM) sleep in sexually potent men. Hypoxia is also a physiological condition at altitude. The level of inspired oxygen decreases progressively with the increase of altitude; for this reason, this study was performed to evaluate the relationship of SREs with hypoxic environment. SREs have been recorded by an erectometer (RigiScan) on three mountain climbers (mean age: 32.5) during a 26-day stay at an altitude ranging from 2000 to 5600 m above sea level. Twenty-four records have been made at progressively increasing altitudes. A data analysis was carried out on a statistical mean of the three values of each variable and an analysis of variance (ANOVA) and Newman-Keuls test were carried out for multiple comparison among groups. At altitudes over 4450 m, we found lack of rigidity at 80-100% and 60-79%. Mean % of rigidity and rigidity time of 80-100% (tip and base) decreased progressively with altitude. No significant reductions were shown in rigidity time at 0-19% and at 20-39% (tip and base), of total number, of total and mean duration of SREs. Pathological rigidometric records at high altitude in sexually potent men at sea level clarify the primary role of hypoxia in physiopathological ED pathway.