Prolonged High Altitude Exposure Research Articles

Chronic hypoxia disrupts memory T regulatory cell phenotype which contributes to the pathogenesis of pulmonary hypertension

Pulmonary hypertension (PH) caused by chronic hypoxia (CH) is a multifaceted disease most often caused by sleep apnea, prolonged high-altitude exposure, or chronic obstructive pulmonary disease (COPD), with minimal treatment options, leading to right heart failure and death. One major contributor in the pathogenesis of PH that requires more characterization is the accompanying immune response.Our previous studies have demonstrated the importance of inflammation and self-immunity in CH-induced PH. We demonstrated pulmonary-perivascular localization of pro-inflammatory Th17 cells as well as an increase in total Th17 cells in the lung, while finding no overall changes in the number of anti-inflammatory T regulatory (Treg) cells present in the lung. Imbalance between Th17 and Treg cells has been shown to drive multiple inflammatory and metabolic diseases. One area of interest related to this balance has been the recent discovery and attempted characterization of exTregs, or cells that, at one point in time, were Tregs but lost their phenotype transitioning to pro-inflammatory Th17 cells, due to decreases in the expression of the transcription factor FoxP3. Therefore, we hypothesized that the increase in Th17 cells seen in CH is due to a decrease in Tregs and Treg suppressive capacity as well as a switching of Tregs to Th17 cells. Using a mouse model that allows the study of lineage stability and genetic mapping of Tregs, together with single-cell RNA sequencing (scRNA SEQ), we initially established that CH resulted in a gene expression profile consistent with exTregs or Tregs with less suppressive activity, such as downregulation of Il2ra gene and upregulation of Tnfrsf4 (adjusted p-value 0.03). To further establish a loss in Tregs as well as an increase in exTregs following CH exposure, we performed spectral flow cytometry of splenocytes on a Cytek Aurora to look for changes in protein expression and cell prevalence. Finally, we used a similar lineage mapping mouse model to look at Th17 cells. Following these experiments, we found supporting evidence of our scRNA SEQ data, finding a decrease in Tregs in both male and female mice following CH exposure, as well as an increase in exTregs in both groups exposed to CH. We also further supported this data finding Th17 cells tracked through our model to be increased following CH. These results support the importance of immune cell balance and inflammation in the pathogenesis of CH-induced PH. R56 HL153065-01 NIH, AHA 18TPA34170037, AHA967925 & T32 HL07736 NIH 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.

The coronary vascular response to the metaboreflex at low altitude and during acute and prolonged high altitude in males

Myocardial oxygen delivery is primarily regulated through changes in vascular tone to match increased metabolic demands. In males, activation of the muscle metaboreflex during acute isocapnic hypoxia results in paradoxical coronary vasoconstriction. Whether coronary blood velocity is reduced by metaboreflex activation following travel and/or adaptation to high altitude is unknown. This study determined if the response of the coronary vasculature to muscle metaboreflex activation at low altitude differs from acute (1/2 days) and prolonged (8/9 days) high altitude. Healthy males (n = 16) were recruited and performed isometric handgrip exercise (30% max) followed by postexercise circulatory occlusion (PECO) to isolate the muscle metaboreflex at low altitude and following acute and prolonged high altitude (3,800 m). Mean left anterior descending coronary artery blood velocity (LADvmean, transthoracic Doppler echocardiography), heart rate, mean arterial pressure (MAP), ventilation, and respired gases were assessed during baseline and PECO at all time points. Coronary vascular conductance index (CVCi) was calculated as LADVmean/MAP. The change in LADvmean (acute altitude: -1.7 ± 3.9 cm/s, low altitude: 2.6 ± 3.4 cm/s, P = 0.01) and CVCi (acute altitude: -0.05 ± 0.04 cm/s/mmHg, low altitude: -0.01 ± 0.03 cm/s/mmHg, P = 0.005) induced by PECO differed significantly between acute high altitude and low altitude. The change in LADVmean and CVCi induced by PECO following prolonged high altitude was not different from low altitude. Our results suggest that coronary vasoconstriction with metaboreflex activation in males is greatest following acute ascent to high-altitude and restored to low-altitude levels following 8-9 days of acclimatization.NEW & NOTEWORTHY Coronary blood flow is regulated by both local metabolic signaling pathways and adrenergic activity in healthy humans. The integrated effects of these systems on coronary vascular physiology are not well understood. Using Doppler echocardiography, this study demonstrates that adrenergic stimulation caused by metaboreflex activation leads to greater reductions in coronary vascular conductance following acute high-altitude but not after prolonged high-altitude exposure.

Hypobaric hypoxia deteriorates bone mass and strength in mice.

Mountaineers at high altitude are at increased risk of acute mountain sickness as well as high altitude pulmonary and cerebral edema. A densitometric study in mountaineers has suggested that expeditions at high altitude decrease bone mineral density. Surprisingly, the in vivo skeletal effects of hypobaric hypoxia are largely unknown, and have not been studied using advanced contemporary methods to assess bone microstructure. Eighty-four 22-week-old female mice were divided into seven groups with 12 mice in each group: 1. Baseline; 2. Normobaric, 4weeks; 3. Hypobaric hypoxia, 4weeks; 4. Normobaric, 8weeks; 5. Hypobaric hypoxia, 8weeks; 6. Normobaric, 12weeks; and 7. Hypobaric hypoxia, 12weeks. Hypobaric hypoxia mice were housed in hypobaric chambers at an ambient pressure of 500mbar (5500m altitude), while normobaric mice were housed at sea level atmospheric pressure for 4, 8, or 12weeks, respectively. Hypobaric hypoxia had a profound impact on femoral cortical bone and L4 trabecular bone, while the effect on femoral trabecular bone was less pronounced. Hypobaric hypoxia reduced the bone strength of the femoral mid-diaphysis and L4 at all time-points. At femoral cortical bone, hypobaric hypoxia reduced bone formation through fewer mineralizing surfaces and lower bone formation rate after 2weeks. In addition, bone strength decreased, and C-terminal telopeptide of type I collagen (CTX-I) increased independently of the duration of exposure to simulated high altitude. At L4, hypobaric hypoxia resulted in a substantial reduction in bone volume fraction, trabecular thickness, and trabecular number after 4weeks of exposure. Hypobaric hypoxia reduced bone strength and femoral bone mass, while femoral trabecular bone was much less affected, indicating the skeletal response to hypobaric hypoxia differ between cortical and trabecular bone. These findings provide initial preclinical support for future clinical studies in mountaineers to assess bone status and bone strength after exposure to prolonged high altitude exposure.

MEDEX 2015: Prophylactic Effects of Positive Expiratory Pressure in Trekkers at Very High Altitude.

Purpose: Positive expiratory pressure (PEP) breathing has been shown to increase arterial oxygenation during acute hypoxic exposure but the underlying mechanisms and consequences on symptoms during prolonged high-altitude exposure remain to be elucidated.Methods: Twenty-four males (41 ± 16 years) were investigated, at sea level and at 5,085 m after 18 days of trekking from 570 m. Participants breathed through a face-mask with PEP = 0 cmH2O (PEP0, 0–45th min) and with PEP = 10 cmH2O (PEP10, 46–90th min). Arterial (SpO2), quadriceps and prefrontal (near infrared spectroscopy) oxygenation was measured continuously. Middle cerebral artery blood velocity (MCAv, transcranial Doppler), cardiac function (2D-echocardiography), extravascular lung water accumulation (UsLC, thoracic ultrasound lung comets) and acute mountain sickness (Lake Louise score, LLS) were assessed during PEP0 and PEP10.Results: At 5,085 m with PEP0, SpO2 was 78 ± 4%, UsLC was 8 ± 5 (a.u.) and the LLS was 2.3 ± 1.7 (all P < 0.05 versus sea level). At 5,085 m, PEP10 increased significantly SpO2 (+9 ± 5%), quadriceps (+2 ± 2%) and prefrontal cortex (+2 ± 2%) oxygenation (P < 0.05), and decreased significantly MCAv (−16 ± 14 cm.s–1) and cardiac output (−0.7 ± 1.2 L.min–1) together with a reduced stroke volume (−9 ± 15 mL, all P < 0.05) and no systemic hypotension. PEP10 decreased slightly the number of UsLC (−1.4 ± 2.7, P = 0.04) while the incidence of acute mountain sickness (LLS ≥ 3) fell from 42% with PEP0 to 25% after PEP10 (P = 0.043).Conclusion: PEP10 breathing improved arterial and tissue oxygenation and symptoms of acute mountain sickness after trekking to very high altitude, despite reduced cerebral perfusion and cardiac output. Further studies are required to establish whether PEP-breathing prophylactic mechanisms also occur in participants with more severe acute mountain sickness.

Cerebral haemodynamics and oxygenation during whole-body exercise over 5days at high altitude.

What is the central question of this study? Impairment and subsequent improvement in cerebral oxygenation during acute and prolonged exposure to high altitude affect exercise performance. This study innovates by investigating the effect of acute and prolonged high-altitude exposure on cerebral haemodynamics during submaximal endurance exercise performed at the same relative intensity. What is the main finding and its importance? Despite exercising at the same relative intensity at sea level and high altitude, participants showed a sustained impairment in cerebral oxygenation after prolonged exposure to high altitude, which might contribute to the absence of improvement in exercise tolerance. Deterioration and subsequent improvement in cerebral oxygenation during acute and prolonged hypoxic exposure may affect whole-body exercise performance at high altitude. In this study, we investigated the effect of hypoxic exposure on cerebral haemodynamics at different cortical locations during exercise at the same relative intensity after 1 (D1) and 5days (D5) at 4350m. Eleven male subjects performed a submaximal bout of cycling exercise (6min at 35%+6min at 55% + time-to-exhaustion at 75% of peak work rate achieved in the same conditions, i.e. normoxia or hypoxia at sea level) on D1 and D5. Transcranial Doppler and near-infrared spectroscopy were used to assess middle cerebral artery blood velocity and prefrontal and motor cortex oxygenation, respectively. Despite using the same relative intensity, the duration of exercise was reduced on D1 (22.7±5.1min) compared with sea level (32.2±9.0min; P<0.001), with no improvement on D5 (20.9±6.3min; P>0.05). Middle cerebral artery blood velocity during exercise was elevated on D1 (+18.2%) and D5 (+15.0%) compared with sea level (P<0.001). However, prefrontal and motor cortex oxygenation was reduced on D1 and D5 compared with sea level (P<0.001). This pattern was of similar magnitude between cortical locations, whereas the total haemoglobin concentration increased to a greater extent in the prefrontal versus motor cortex at exhaustion on D1 and D5. In contrast to our primary hypothesis, prefrontal and motor cortex oxygenation and exercise performance did not improve over 5days at 4350m. The sustained impairment in cerebral oxygenation might contribute to the absence of improvement in exercise performance after partial acclimatization to high altitude.

Prolonged high altitude exposure exacerbates fat‐free mass and fat mass loss during negative energy balance regardless of dietary protein intake

Protein intake above the recommended dietary allowance attenuates fat‐free mass (FFM) loss during moderate negative energy balance (~40% energy deficit) at sea level (SL). Sustained periods of strenuous physical activity at high altitude (HA) may exacerbate FFM loss, especially during energy deficit. However, increased dietary protein intake has not been evaluated as a countermeasure to FFM loss at HA. This study aimed to determine whether consuming dietary protein at amounts consistent with current recommendations for elevated physical activity (2.0 g protein/kg) attenuates FFM loss during prolonged energy deficit at HA. Seventeen healthy males (mean ± SD, 23.4 ± 5.6y, 81.9± 13.9 kg) participated in a 2‐phase, 43‐d study. During phase 1 (SL), participants were instructed to consume a weight maintenance diet with standard protein intake(1.0 g protein/kg, STD) for 21 d. During phase 2, participants resided at HA (4300 m, Pikes Peak, CO) for 22 d and were randomly assigned to either a STD or high (2.0 g protein/kg, HIGH) protein diet designed to elicit a 40% energy deficit (30% dietary restriction and 10% increase in physical activity, estimated energy deficit was 1074 ± 122 kcal/d based on the total energy requirements necessary to maintain body mass during phase 1) and~3 kg total body mass loss. Diet and physical activity were highly controlled. Total body mass, FFM, and fat mass (FM) were assessed by dual energy x‐ray absorptiometry and resting metabolic rate (RMR) by indirect calorimetry. Volunteers were weight stable during SL and lost −7.9 ± 1.9 kg(P&lt;0.01)during HA, regardless of protein group (P&gt;0.05). Decrements in FFM (−4.0 ± 3.3 vs. −3.2 ± 1.5 kg) and FM (−3.3 ± 1.8 vs. −3.9 ± 0.8 kg) were not statistically different between STD and HIGH (P&gt;0.05). The overall energy deficit was 2306 ± 444kcal/d when calculated based on changes in FFM and FM. The additional energy deficit was attributable, in part, to an increase in RMR, which peaked at 58%above SL on HA day 1 and remained ≥ 25% higher than SL throughout HA(P&lt;0.05), accounting for 27% (634 ± 273 kcal/d) of the total energy deficit at HA. The remaining 598 kcal/d (26% of total deficit) could not be accounted for by estimated energy expenditure of prescribed daily physical activity and measured energy intake, suggesting the energy cost of physical activity may be greater at HA than SL. Prolonged HA exposure exacerbated the catabolic effects of negative energy balance. In this context, consuming a higher versus standard protein diet was equally ineffective at sparing FFM with weight loss. The opinions or assertions contained herein are the private views of the author(s)and are not to be construed as official or reflecting the views of the Army or the Department of Defense.Support or Funding InformationSupported by USAMRMC.

Prolonged High Altitude Exposure Results in Elevated Erythroferrone and Diminished Hepcidin Levels in Healthy Young Male Volunteers

Iron, an essential micronutrient, supports physical and cognitive performance through the binding of proteins and enzymes involved in oxygen transport and energy metabolism. High altitude (HA) acclimatization affects iron metabolism and results in increased hemoglobin concentrations due to hypoxia‐stimulated hemoconcentration and erythropoeisis. Iron homeostasis is regulated by hepcidin, aprotein affecting iron absorption and metabolism through the binding and degradation of ferroportin, the primary cellular iron exporter. Erythroferrone, a recently identified hormone, inhibits hepcidin transcription during erythropoiesis in animal models. As hepcidin and erythroferrone have not been assessed in human volunteers exposed to HA, the primary objective of the present study was to explore the effects of HA on hepcidin, erythroferrone, andiron availability. Hemoglobin, hepcidin, erythroferrone, and serum iron were measured in unacclimatized healthy youngmen (n = 17, age [mean ± SD] = 23.4 ± 5.6 yrs, body weight = 81.9 ± 13.9 kg) residing at sea level(SL) and HA (19 d, 4300 m). While residing at HA, volunteers consumed energy restricted diets providing 70% of SL weight maintenance energy needs, and engaged in prescribed physical activity to induce a 40% total daily energy deficit. As compared to SL, HA resulted in increased hemoglobin (16.6 ± 0.9 vs. 14.3 ± 0.8 g/dL, P &lt;0.01), diminished hepcidin (4.8± 3.4 vs. 7.5 ± 3.4 ng/mL, P &lt;0.05), and increased erythroferrone (3.1 ± 2.1 vs. 0.9 ± 0.6pg/mL, P &lt; 0.01). Serum iron increased at HA as compared to SL (104.7 ± 34.2 vs. 65.4 ± 17.4μg/mL, P &lt; 0.01). Taken together, these data indicate that prolonged HA exposure in humans results in elevated erythroferrone, which is associated with suppressed hepcidin transcription and increased iron availability.Support or Funding InformationResearch supported by the US Army Medical Research and Materiel Command. The views expressed in this abstract are those of the authors and do not reflect the official policy of the Department of Army, Department of Defense, or the US Government.

Multiparametric Magnetic Resonance Investigation of Brain Adaptations to 6 Days at 4350 m.

Objective: Hypoxic exposure in healthy subjects can induce acute mountain sickness including headache, lethargy, cerebral dysfunction, and substantial cerebral structural alterations which, in worst case, can lead to potentially fatal high altitude cerebral edema. Within this context, the relationships between high altitude-induced cerebral edema, changes in cerebral perfusion, increased brain parenchyma volume, increased intracranial pressure, and symptoms remain unclear.Methods: In 11 subjects before and after 6 days at 4350 m, we performed multiparametric magnetic resonance investigations including anatomical, apparent diffusion coefficient and arterial spin labeling sequences.Results: After the altitude stay, while subjects were asymptomatic, white matter volume (+0.7 ± 0.4%, p = 0.005), diffusion (+1.7 ± 1.4%, p = 0.002), and cerebral blood flow (+28 ± 38%; p = 0.036) were significantly increased while cerebrospinal fluid volume was reduced (−1.4 ± 1.1%, p = 0.009). Optic nerve sheath diameter (used as an index of increased intracranial pressure) was unchanged from before (5.84 ± 0.53 mm) to after (5.92 ± 0.60 mm, p = 0.390) altitude exposure. Correlations were observed between increases in white matter volume and diffusion (rho = 0.81, p = 0.016) and between changes in CSF volume and changes in ONSD s (rho = −0.92, p = 0.006) and symptoms during the altitude stay (rho = −0.67, p = 0.031).Conclusions: These data demonstrate white matter alterations after several days at high altitude when subjects are asymptomatic that may represent the normal brain response to prolonged high altitude exposure.

Cognitive functions and cerebral oxygenation changes during acute and prolonged hypoxic exposure

The present study aimed to assess specific cognitive processes (cognitive control and time perception) and hemodynamic correlates using functional near-infrared spectroscopy (fNIRS) during acute and prolonged high-altitude exposure. Eleven male subjects were transported via helicopter and dropped at 14 272 ft (4 350 meters) of altitude where they stayed for 4 days. Cognitive tasks, involving a conflict task and temporal bisection task, were performed at sea level the week before ascending to high altitude, the day of arrival (D0), the second (D2) and fourth (D4) day at high altitude. Cortical hemodynamic changes in the prefrontal cortex (PFC) area were monitored with fNIRS at rest and during the conflict task. Results showed that high altitude impacts information processing in terms of speed and accuracy. In the early hours of exposure (D0), participants displayed slower reaction times (RT) and decision errors were twice as high. While error rate for simple spontaneous responses remained twice that at sea level, the slow-down of RT was not detectable after 2 days at high-altitude. The larger fNIRS responses from D0 to D2 suggest that higher prefrontal activity partially counteracted cognitive performance decrements. Cognitive control, assessed through the build-up of a top-down response suppression mechanism, the early automatic response activation and the post-error adjustment were not impacted by hypoxia. However, during prolonged hypoxic exposure the temporal judgments were underestimated suggesting a slowdown of the internal clock. A decrease in cortical arousal level induced by hypoxia could consistently explain both the slowdown of the internal clock and the persistence of a higher number of errors after several days of exposure.

Strain variation in the adaptation of C57Bl6 and BALBc mice to chronic hypobaric hypoxia

The interplay of environmental and genetic factors may lead to a spectrum of physiological and behavioral outcomes. How environmental stress factors interact with the diverse mouse genomes is still poorly understood and elucidating the underlying interactions requires specific stress models that can target integrated physiological systems. Here, we employ behavioral tests and whole-body plethysmography to examine the effects of 12weeks of simulated high altitude (HA) exposure on two inbred mouse strains, BALBc and C57Bl6. We find that HA induced- weight loss recovers at significantly different rates in these two strains. Even at 12weeks, however, both strains fail to reach body weight levels of controls. Performance on two motor tasks, rotarod and treadmill, improve with HA exposure but more prominently in BALBc mice. Whole-body plethysmography outcomes indicate that compensation to chronic HA includes increased respiratory frequencies and tidal volumes in both strains. However, the effects on tidal volume are significantly greater in BALBc mice and showed a biphasic course. Whole- body metabolic rates are also increased in both strains with prolonged HA exposure, but were more pronounced in BALBc mice suggestive of less successful adaptation in this strain. These adaptations occur in the absence of gross pathological changes in all major organs. Together these results indicate that chronic HA exposure results in environmental stressors that impact the specific physiological responses of BALBc more than C57Bl6 mice. Thus, these strains provide a promising platform for investigating how genetic backgrounds can differentially reinforce the effects of long-lasting environmental stressors and their potential to interact with psychological stressors.

Changes in 24 h ambulatory blood pressure and effects of angiotensin II receptor blockade during acute and prolonged high-altitude exposure: a randomized clinical trial.

Many hypertensive subjects travel to high altitudes, but little is known on ambulatory blood pressure (ABP) changes and antihypertensive drugs' efficacy under acute and prolonged exposure to hypobaric hypoxia. In particular, the efficacy of angiotensin receptor blockers in this condition is unknown. This may be clinically relevant considering that renin-angiotensin system activity changes at altitude. The HIGHCARE-HIMALAYA study assessed changes in 24 h ABP under acute and prolonged exposure to increasing altitude and blood pressure-lowering efficacy and safety of an angiotensin receptor blockade in this setting. Forty-seven healthy, normotensive lowlanders were randomized to telmisartan 80 mg or placebo in a double-blind, parallel group trial. Conventional and Ambulatory BPs were measured at baseline and on treatment: after 8 weeks at sea level, and under acute exposure to 3400 and 5400 m altitude, the latter upon arrival and after 12 days (Mt. Everest base camp). Blood samples were collected for plasma catecholamines, renin, angiotensin, and aldosterone. In both groups, exposure to increasing altitude was associated with: (i) significant progressive increases in conventional and 24 h blood pressure, persisting throughout the exposure to 5400 m; (ii) increased plasma noradrenaline and suppressed renin-angiotensin-aldosterone system. Telmisartan lowered 24 h ABP at the sea level and at 3400 m (between-group difference 4.0 mmHg, 95% CI: 2.2-9.5 mmHg), but not at 5400 m. Ambulatory blood pressure increases progressively with increasing altitude, remaining elevated after 3 weeks. An angiotensin receptor blockade maintains blood pressure-lowering efficacy at 3400 m but not at 5400 m.

Cardiopulmonary Response and Body Composition Changes after Prolonged High Altitude Exposure in Women

Weight loss in men is commonly observed during prolonged high altitude exposure as a result of a daily negative energy balance. Its amount depends mainly on duration of exposure, altitude reached, and level of physical activity. This reduction in body weight often comes with a loss of muscular mass, likely contributing to the decreased physical performance generally reported. Limited data is, however, available on body composition, functional capacity, and cardiopulmonary response to exercise after high altitude exposure in women. The aim of this study was to evaluate the effects of prolonged high altitude exposure on body composition and on cardiopulmonary response to maximal exercise in a group of young, moderately active women. Twelve female subjects, aged 21.5 ± 3.1 (mean ± SD), BMI 22.1 ± 1.9 kg · m(-2) and Vo(2max) 33.8 ± 3.5 mL · kg(-1) · min(-1), participated in this study, by residing for 21 days at high altitude (5050 m, Pyramid, EV-K(2)-CNR laboratory). Before and after high altitude exposure, all subjects underwent both a body composition evaluation using two methods (bioimpedance analysis and DEXA) and a functional evaluation based on a maximal exercise test on a cycle ergometer with breath-by-breath gas analysis. After high altitude exposure, data showed a slight, nonsignificant reduction in body weight, with an average 3:2 reduction ratio between fat and fat-free mass evaluated by DEXA, in addition to a significant decrease in Vo(2max) on the cycle ergometer test (p<0.01). Changes in Vo(2max) correlated to changes of leg muscle mass, evaluated by DEXA (r(2) = 0.72; p<0.0001). No changes were observed in the maximal heart rate, work capacity, and ventilatory thresholds, while the Vo(2)/W slope was significantly reduced (p<0.05). Finally, Ve/Vo(2) and VE/Vco(2max) slopes were increased (p<0.01), suggesting a possible long-term modulation of the exercise ventilatory response after prolonged high altitude exposure.

Cardiopulmonary Response And Body Composition Changes After A Prolonged High Altitude Exposure In Women

Cardiopulmonary Response And Body Composition Changes After A Prolonged High Altitude Exposure In Women

Plasma proANP 1-98 Response During High Altitude Stress: Effect of Age and Ethnicity

Acclimatization to high altitude (HA) is accompanied by decrease in plasma atrial natriuretic peptide (ANP). On the other hand, circulating levels of the hormone are known to be influenced by age and ethnicity. The impact of these factors on ANP response during prolonged HA exposure remains unexplored. Hence, this study was conducted to examine possible age and ethnic variation in plasma proANP(1-98) levels in men after 3 to 4 weeks at HA. Lowlanders (LL) were studied at sea level (SL) and after 3 to 4 weeks at an altitude of approximately 4500 m. The LL group comprised Rajput (n = 48), Gorkha (n = 40), and South Indian (n = 43) ethnicities. Another group of HA natives (Ladakhi, n = 40) were studied at approximately 4500 m only. Subjects were between 20 and 50 years of age. Estimation of plasma proANP(1-98) and biochemical, hematologic, and physiologic evaluation was done. In LL at HA, proANP(1-98) levels decreased (P < .001); plasma arginine vasopressin decreased (P < .05 in Rajputs and South Indians); and total protein, hemoglobin, and hematocrit increased (P < .05). Heart rate increased (P < .05), whereas arterial oxygen saturation decreased (P < .05) in all LL at HA. Ethnicity but not age variation in proANP(1-98) was observed under HA stress. In HA natives, plasma proANP(1-98) was higher than LL at HA and did not exhibit any age variation. Plasma proANP(1-98) levels, reflecting medium-term ANP secretion, decrease during prolonged exposure to HA in LL. This is due to diuresis leading to plasma volume reduction that occurs during the acclimatization process. Ethnicity but not age variation is associated with plasma proANP(1-98) under HA stress.

Impact of Prolonged High Altitude Exposure on Plasma Prolactin in Men: Effect of Age and Ethnicity

Hormonal changes during high-altitude (HA) exposure are important for normal adaptation to the new environment in lowlanders. Prolactin (PRL), a stress hormone, is involved in the regulation of fertility, immune response, osmotic balance, and angiogenesis. However, little is known about the effect of age and ethnicity on plasma PRL changes in men during prolonged HA exposure. The aim of this research was to examine possible age and ethnic variation in plasma PRL levels in men after 3 to 4 weeks of stay at HA (approximately 4500 m) in the Indian population. Lowlanders of Rajput (n = 49), Gorkha (n = 70), and South Indian (n = 40) ethnicities were studied at sea level (SL). They were taken to an altitude of approximately 4500 m where they stayed for 3 to 4 weeks. Another group of HA natives (Ladakhi, n = 65) was studied at similar altitude. Subjects were between 20 to 50 yr of age. At HA, plasma PRL showed a decrease in Rajputs and Gorkhas (p < 0.05), whereas there was an increase (p < 0.05) in South Indians when compared to SL. There was no age variation in PRL. PRL levels in HA natives were within the SL normal range observed in lowlanders. PRL response to HA stress in lowlanders is influenced by ethnicity. The exact cause for such differences in PRL secretion under HA stress is not clearly known. Further studies on the physiological regulation of PRL at HA are needed.

Effect of altitude on leptin levels, does it go up or down?

reports of a relationship between altitude and circulating levels of leptin suggest a possible role of hypoxia in leptin regulation. However, studies on the changes in plasma leptin levels at altitude are controversial, with some showing an increase and others suggesting no change or a fall in these

O desafio da altitude. Uma perspectiva fisiológica

The High-Altitude Challenge. A Physiological Point of View High-altitude physical activities have been widely performed in the later years. Activities like mountaineering, climbing and skiing, demanding short or prolonged high-altitude exposure, induce strenuous physiological exertion as a consequence of hypobaric hypoxic environmental conditions. The present work reviews the main acute and chronic physiological adaptations on (i) the respiratory and cardiovascular systems, (ii) hematological components and (iii) muscular morphology and metabolism, allowing the maintenance of life and practice of physical activities on high-altitude hostile regions. Finally, is briefly reviewed the state of the art on altitude training concerning the physiological and sports benefits to perform at sea level.

Operation Everest III: role of plasma volume expansion on VO(2)(max) during prolonged high-altitude exposure.

We hypothesize that plasma volume decrease (DeltaPV) induced by high-altitude (HA) exposure and intense exercise is involved in the limitation of maximal O(2) uptake (VO(2)(max)) at HA. Eight male subjects were decompressed for 31 days in a hypobaric chamber to the barometric equivalent of Mt. Everest (8,848 m). Maximal exercise was performed with and without plasma volume expansion (PVX, 219-292 ml) during exercise, at sea level (SL), at HA (370 mmHg, equivalent to 6, 000 m after 10-12 days) and after return to SL (RSL, 1-3 days). Plasma volume (PV) was determined at rest at SL, HA, and RSL by Evans blue dilution. PV was decreased by 26% (P < 0.01) at HA and was 10% higher at RSL than at SL. Exercise-induced DeltaPV was reduced both by PVX and HA (P < 0.05). Compared with SL, VO(2)(max) was decreased by 58 and 11% at HA and RSL, respectively. VO(2)(max) was enhanced by PVX at HA (+9%, P < 0.05) but not at SL or RSL. The more PV was decreased at HA, the more VO(2)(max) was improved by PVX (P < 0.05). At exhaustion, plasma renin and aldosterone were not modified at HA compared with SL but were higher at RSL, whereas plasma atrial natriuretic factor was lower at HA. The present results suggest that PV contributes to the limitation of VO(2)(max) during acclimatization to HA. RSL-induced PVX, which may be due to increased activity of the renin-aldosterone system, could also influence the recovery of VO(2)(max).

Body fluids, atrial volumes and atrial natriuretic peptide during and after high-altitude exposure

The aim of this investigation was to assess the changes of atrial volumes during and after prolonged high-altitude exposure, in relation to extracellular and total body water and plasma levels of atrial natriuretic peptide (ANP). The estimation of extracellular and total body water was obtained by bioelectrical impedance measurement in seven healthy male subjects aged 24.7 years (range 23-28). These were members of a Himalayan expedition (Pumori, 7135 m). Measurements were taken before departure, after 1 and 4 weeks at altitude over 5000 m, and upon return to sea level. In the same phases, right and left atrial volumes were determined by 2D-echocardiography and blood samples were drawn for ANP by radioimmunoassay. At high altitude, body fluid depletion, as shown by reduction of extracellular and total body water, was related to reduction of left atrial volume, whereas the right atrium did not show any significant change. Upon return to sea level, the persistence of reduced extracellular and total body water went along with the persistence of decreased left atrial volume. Despite the wide variability in plasma levels of ANP among subjects, a clear-cut reduction was observed in all subjects after 4 weeks at high altitude, and a significant ( p During prolonged high altitude exposure, progressive reduction of left atrial volume reflects body fluid depletion; after 4-week exposure, circulating ANP levels decrease concomitant with left atrial volume reduction.

Cardiovascular neural regulation during and after prolonged high altitude exposure.

Eight young healthy male subjects, members of a Himalayan expedition, underwent 24 h Holter monitoring before departure, after 1 and 4 weeks at high altitude (5000 m) and after return to sea level. At high altitude, the circadian reciprocal changes in low and high frequency (LF, HF) were absent, with no significant reduction in the LF to HF ratio over the 24 h; moreover, the proportion of adjacent R-R intervals that differed by more than 50 ms (pNN50) decreased significantly and remained lower after return to sea level. Urine catecholamines increased at high altitude, but only norepinephrine, after 1 week of exposure, rose significantly. Upon return to sea level the density, but not the affinity, of [alpha]2-adrenergic receptors on platelets decreased significantly compared to pre-expedition values. At high altitude increased sympathetic activity was indicated by elevation of urine norepinephrine and by the loss of circadian rhythm in spectral components. The simultaneous reduction of HF and pNN50 demonstrated decreased vagal tone. The persistence of increased sympathetic activity could explain the downregulation of adrenergic receptors after prolonged high altitude exposure.