Sea-level Residents Research Articles

Investigating Sea-Level Brain Predictors for Acute Mountain Sickness: A Multimodal MRI Study before and after High-Altitude Exposure.

Acute mountain sickness is a series of brain-centered symptoms that occur when rapidly ascending to high altitude. Predicting acute mountain sickness before high-altitude exposure is crucial for protecting susceptible individuals. The present study aimed to evaluate the feasibility of predicting acute mountain sickness after high-altitude exposure by using multimodal brain MR imaging features measured at sea level. We recruited 45 healthy sea-level residents who flew to the Qinghai-Tibet Plateau (3650 m). We conducted T1-weighted structural MR imaging, resting-state fMRI, and arterial spin-labeling perfusion MR imaging both at sea level and high altitude. Acute mountain sickness was diagnosed for 5 days using Lake Louise Scoring. Logistic regression with Least Absolute Shrinkage and Selection Operator logistic regression was performed for predicting acute mountain sickness using sea-level MR imaging features. We also validated the predictors by using MR images obtained at high altitude. The incidence rate of acute mountain sickness was 80.0%. The model achieved an area under the receiver operating characteristic curve of 86.4% (sensitivity = 77.8%, specificity = 100.0%, and P < .001) in predicting acute mountain sickness At sea level, valid predictors included fractional amplitude of low-frequency fluctuations (fALFF) and degree centrality from resting-state fMRI, mainly distributed in the somatomotor network. We further learned that the acute mountain sickness group had lower levels of fALFF in the somatomotor network at high altitude, associated with smaller changes in CSF volume and higher Lake Louise Scoring, specifically relating to fatigue and clinical function. Our study found that the somatomotor network function detected by sea-level resting-state fMRI was a crucial predictor for acute mountain sickness and further validated its pathophysiologic impact at high altitude. These findings show promise for pre-exposure prediction, particularly for individuals in need of rapid ascent, and they offer insight into the potential mechanism of acute mountain sickness.

Comparative Study of Complete Blood Count Between High-Altitude and Sea-Level Residents in West Saudi Arabia.

The reduction in oxygen partial pressure at high altitudes leads to diminished oxygen saturation in the arteries, stimulating erythropoietin production and erythropoiesis to restore appropriate oxygenation. While many studies have explored acclimatization to high altitude and its effects on complete blood count (CBC) parameters, our research uniquely examined both male and female healthy individuals, emphasizing the novelty of gender-specific observations. We analyzed 1,160 individuals in Taif (Al Hada), east Saudi Arabia, a high-altitude region, and compared them to 1,044 counterparts in Jeddah, at sea level. Our results revealed significant variations in CBC parameters, including white blood count, red blood count, hemoglobin, hematocrit, platelets, neutrophils, lymphocytes, monocytes, eosinophils, and basophils, reflecting the body's hypoxic response. These variations were observed in both genders, with specific differences noted between males and females. For example, NEU (neutrophils), representing the absolute count of a type of white blood cell essential in the immune system's defense, showed significant variations for males. The male results show that the variation in males between the sea level and high altitudes indicated significant p-values for all CBC parameters except NEU between at sea level (Jeddah city), whose p-value was 0.8696, and at high altitude (Taif city, Al Hada). In contrast, MONO (monocytes), another type of white blood cell involved in immune response, and RBC (red blood cells), responsible for oxygen transport, were mentioned but did not show significant variations for females. The full results for females showed significant results (P<0.0001)for BASO, HCT, HGB, MCH, MCHC, MPV, PLT, RDW, and WBC between the sea-level altitude and high altitude for females. Also, EOS and LYM showed significant P-values of 0.0002 and 0.0001, respectively, while MONO, NEU, and RBC indicated no significance between the sea-level altitude and high altitude for females. The p-values of MONO, NEU, and RBC, respectively, were0.1907, 0.1259, and 0.0677. The results for both genders combined showed significant variations of all CBC parameters (P<0.0001) between the sea-level altitude and high altitude except for MONO, NEU, and RBC, which were not significant for both males and females, with p-values of 0.1589, 0.2911, and 0.0595, respectively. All unhealthy individuals were excluded from the study with any condition that would cause significant changes in CBC parameters and would skew the results, ensuring a focus on physiological adaptations in healthy subjects. By comparing healthy individuals and examining each gender separately, this study contributes valuable insights into high-altitude acclimatization, enhancing our understanding of physiological adaptations and potentially guiding health management in such environments within the normal range.

AltitudeOmics: effects of 16 days acclimatization to hypobaric hypoxia on muscle oxygen extraction during incremental exercise.

Acute altitude exposure lowers arterial oxygen content ([Formula: see text]) and cardiac output ([Formula: see text]) at peak exercise, whereas O2 extraction from blood to working muscles remains similar. Acclimatization normalizes [Formula: see text] but not peak [Formula: see text] nor peak oxygen consumption (V̇o2peak). To what extent acclimatization impacts muscle O2 extraction remains unresolved. Twenty-one sea-level residents performed an incremental cycling exercise to exhaustion near sea level (SL), in acute (ALT1) and chronic (ALT16) hypoxia (5,260 m). Arterial blood gases, gas exchange at the mouth and oxy- (O2Hb) and deoxyhemoglobin (HHb) of the vastus lateralis were recorded to assess arterial O2 content ([Formula: see text]), [Formula: see text], and V̇o2. The HHb-V̇o2 slope was taken as a surrogate for muscle O2 extraction. During moderate-intensity exercise, HHb-V̇o2 slope increased to a comparable extent at ALT1 (2.13 ± 0.94) and ALT16 (2.03 ± 0.88) compared with SL (1.27 ± 0.12), indicating increased O2 extraction. However, the HHb/[Formula: see text] ratio increased from SL to ALT1 and then tended to go back to SL values at ALT16. During high-intensity exercise, HHb-V̇o2 slope reached a break point beyond which it decreased at SL and ALT1, but not at ALT16. Increased muscle O2 extraction during submaximal exercise was associated with decreased [Formula: see text] in acute hypoxia. The significantly greater muscle O2 extraction during maximal exercise in chronic hypoxia is suggestive of an O2 reserve.NEW & NOTEWORTHY During incremental exercise muscle deoxyhemoglobin (HHb) and oxygen consumption (V̇o2) both increase linearly, and the slope of their relationship is an indirect index of local muscle O2 extraction. The latter was assessed at sea level, in acute and during chronic exposure to 5,260 m. The demonstrated presence of a muscle O2 extraction reserve during chronic exposure is coherent with previous studies indicating both limited muscle oxidative capacity and decrease in motor drive.

Excessive Erythrocytosis Is Not Associated With Altered Iron Homeostasis in Men From the World's Highest City.

Excessive Erythrocytosis Is Not Associated With Altered Iron Homeostasis in Men From the World's Highest City.

Occlusion preconditioned mice are resilient to hypobaric hypoxia-induced myocarditis and arrhythmias due to enhanced immunomodulation, metabolic homeostasis, and antioxidants defense.

Sea-level residents experience altitude sickness when they hike or visit altitudes above ~2,500 m due to the hypobaric hypoxia (HH) conditions at such places. HH has been shown to drive cardiac inflammation in both ventricles by inducing maladaptive metabolic reprogramming of macrophages, which evokes aggravated proinflammatory responses, promoting myocarditis, fibrotic remodeling, arrhythmias, heart failure, and sudden deaths. The use of salidroside or altitude preconditioning (AP) before visiting high altitudes has been extensively shown to exert cardioprotective effects. Even so, both therapeutic interventions have geographical limitations and/or are inaccessible/unavailable to the majority of the population as drawbacks. Meanwhile, occlusion preconditioning (OP) has been extensively demonstrated to prevent hypoxia-induced cardiomyocyte damage by triggering endogenous cardioprotective cascades to mitigate myocardial damage. Herein, with the notion that OP can be conveniently applied anywhere, we sought to explore it as an alternative therapeutic intervention for preventing HH-induced myocarditis, remodeling, and arrhythmias. OP intervention (6 cycles of 5 min occlusion with 200 mmHg for 5 min and 5 min reperfusion at 0 mmHg - applying to alternate hindlimb daily for 7 consecutive days) was performed, and its impact on cardiac electric activity, immunoregulation, myocardial remodeling, metabolic homeostasis, oxidative stress responses, and behavioral outcomes were assessed before and after exposure to HH in mice. In humans, before and after the application of OP intervention (6 cycles of 5 min occlusion with 130% of systolic pressure and 5 min reperfusion at 0 mmHg - applying to alternate upper limb daily for 6 consecutive days), all subjects were assessed by cardiopulmonary exercise testing (CPET). Comparing the outcomes of OP to AP intervention, we observed that similar to the latter, OP preserved cardiac electric activity, mitigated maladaptive myocardial remodeling, induced adaptive immunomodulation and metabolic homeostasis in the heart, enhanced antioxidant defenses, and conferred resistance against HH-induce anxiety-related behavior. Additionally, OP enhanced respiratory and oxygen-carrying capacity, metabolic homeostasis, and endurance in humans. Overall, these findings demonstrate that OP is a potent alternative therapeutic intervention for preventing hypoxia-induced myocarditis, cardiac remodeling, arrhythmias, and cardiometabolic disorders and could potentially ameliorate the progression of other inflammatory, metabolic, and oxidative stress-related diseases.

The HMOX2 polymorphism contributes to the carotid body chemoreflex in European sea-level residents by regulating hypoxic ventilatory responses.

This study investigates whether a functional single nucleotide polymorphism of HMOX2 (heme oxygenase-2) (rs4786504 T>C) is involved in individual chemosensitivity to acute hypoxia, as assessed by ventilatory responses, in European individuals. These responses were obtained at rest and during submaximal exercise, using a standardized and validated protocol for exposure to acute normobaric hypoxia. Carriers of the ancestral T allele (n = 44) have significantly lower resting and exercise hypoxic ventilatory responses than C/C homozygous carriers (n = 40). In the literature, a hypoxic ventilatory response threshold to exercise has been identified as an independent predictor of severe high altitude-illness (SHAI). Our study shows that carriers of the T allele have a higher risk of SHAI than carriers of the mutated C/C genotype. Secondarily, we were also interested in COMT (rs4680 G > A) polymorphism, which may be indirectly involved in the chemoreflex response through modulation of autonomic nervous system activity. Significant differences are present between COMT genotypes for oxygen saturation and ventilatory responses to hypoxia at rest. In conclusion, this study adds information on genetic factors involved in individual vulnerability to acute hypoxia and supports the critical role of the ≪ O2 sensor ≫ - heme oxygenase-2 - in the chemosensitivity of carotid bodies in Humans.

Inflammatory gene expression during acute high‐altitude exposure

The molecular signalling pathways that regulate inflammation and the response to hypoxia share significant crosstalk and appear to play major roles in high‐altitude acclimatization and adaptation. Several studies demonstrate increases in circulating candidate inflammatory markers during acute high‐altitude exposure, but significant gaps remain in our understanding of how inflammation and immune function change at high altitude and whether these responses contribute to high‐altitude pathologies, such as acute mountain sickness. To address this, we took an unbiased transcriptomic approach, including RNA sequencing and direct digital mRNA detection with NanoString, to identify changes in the inflammatory profile of peripheral blood throughout 3 days of high‐altitude acclimatization in healthy sea‐level residents (n = 15; five women). Several inflammation‐related genes were upregulated on the first day of high‐altitude exposure, including a large increase in HMGB1 (high mobility group box 1), a damage‐associated molecular pattern (DAMP) molecule that amplifies immune responses during tissue injury. Differentially expressed genes on the first and third days of acclimatization were enriched for several inflammatory pathways, including nuclear factor‐κB and Toll‐like receptor (TLR) signalling. Indeed, both TLR4 and LY96, which encodes the lipopolysaccharide binding protein (MD‐2), were upregulated at high altitude. Finally, FASLG and SMAD7 were associated with acute mountain sickness scores and peripheral oxygen saturation levels on the first day at high altitude, suggesting a potential role of immune regulation in response to high‐altitude hypoxia. These results indicate that acute high‐altitude exposure upregulates inflammatory signalling pathways and might sensitize the TLR4 signalling pathway to subsequent inflammatory stimuli. Key points Inflammation plays a crucial role in the physiological response to hypoxia.High‐altitude hypoxia exposure causes alterations in the inflammatory profile that might play an adaptive or maladaptive role in acclimatization.In this study, we characterized changes in the inflammatory profile following acute high‐altitude exposure.We report upregulation of novel inflammation‐related genes in the first 3 days of high‐altitude exposure, which might play a role in immune system sensitization.These results provide insight into how hypoxia‐induced inflammation might contribute to high‐altitude pathologies and exacerbate inflammatory responses in critical illnesses associated with hypoxaemia.

High-altitude exposure duration dependent global and regional gray matter volume decrease in healthy immigrants: a cross-sectional study.

The correlation between brain injury and high-altitude (HA) exposure duration (Dur_HA) as well as peripheral oxygen saturation (SpO2) remains unclear. To evaluate the global and regional brain volume differences between HA immigrants and sea-level residents, and the relationship between brain volume with Dur_HA and SpO2. Structural magnetic resonance imaging (MRI) scans were acquired in 33 healthy male HA immigrants (HA group) and 33 matched sea-level male residents (SL group). Differences in global gray matter volume (GMV), white matter volume (WMV), brain parenchyma volume (BV), total intracranial volume (TIV), and the volume-fraction (the ratio of GMV/TIV, WMV/TIV, BV/TIV) were assessed. Regional gray matter differences were investigated using voxel-based morphology analysis. The volume of clusters with GM loss were calculated as the volume of volume of interest (V_VOI). Student's t-test and partial correlation were adopted for statistic calculation. Compared to the SL group, the HA immigrants had larger WMV (P = 0.015), smaller ratio of GMV/WMV (P = 0.022), and regional gray matter loss in bilateral basal ganglion, limbic system, midbrain, and vermis (cluster size >100 voxels, family-wise error corrected at P = 0.01). The global GMV, BV, and V_VOI confined to vermis had negative correlations with the Dur_HA (r = -0.369, P = 0.049; r = -0.380, P = 0.042; and r = -0.471, P = 0.010. Neither global nor regional brain volume correlated with SpO2. Global and regional brain are affected by long-term HA exposure, and global and regional gray matter have a time-dependent volume loss.

Cardiac adaptation to high altitudes after short- and long-term exposure among Chinese Han lowlanders.

Short-term, high altitude (HA) exposure raises pulmonary artery systolic pressure (PASP) and decreases left ventricular volumes. However, relatively little is known of the long-term cardiac consequences of prolonged exposure in Chinese Han lowlanders, a highly adapted HA population. We studied cardiac structure and function by echocardiography to investigate short-term adaptation and potential long-term cardiac remodeling. This study included 301 healthy subjects of short-term exposure (STE), acclimatized Chinese Han lowlanders (AL) at HA, native Tibetans (NT), and sea level residents (SLR) with 75, 77, 69, and 80 participants, respectively. All groups underwent standard echocardiography. Compared with SLR, systolic blood pressure (SBP) and heart rate of STE and AL did not significantly increase following HA exposure, but SBP in STE was lower than AL. In lowlanders, HA exposure enlarged right heart and pulmonary artery (PA), reduced left ventricular (LV) diastolic function. This decrease in LV diastolic function increased with exposure time. Compared with SLR, ejection fraction did not change significantly in STE, but decreased in AL. Interventricular septal end-diastolic thickness (IVSd) increased both in STE and AL compared with SLR. Compared with NT, AL population had higher SBP and the greater diameter of PA. In Chinese Han lowlanders, exposure to HA enlarged right ventricle and decreased the diastolic function of LV. LV systolic function was preserved after short-term HA exposure but decreased after long-term HA exposure. It was possible to speculate that ethnicity contributed to the observed difference in heart.

Adaptation to Moderate Altitude Hypoxemia: The Example of the Valley of Mexico.

A large world population resides at moderate altitude. In the Valley of Mexico (2,240 m above sea level), its inhabitants, breathe approximately 29% more on average and have 10% increased hemoglobin concentrations compared to sea level residents, among other differences. These compensations reduce but not eliminate the impact of altitude hypoxemia. The objective of the manuscript is to review and describe the information available on health and disease at moderate altitudes, mainly with data in Spanish language from Latin-American countries. Young adults in Mexico City have an SaO2 between 92% and 94% versus 97% at sea level, frequently decreasing below 90% during sleep and intense exercise. It is likely that among the population living at this altitude, lung growth, and development during pregnancy and infancy are enhanced, and that after residing for several tens of thousands of years, more important adaptations in oxygen transport and utilization have developed, but we are not certain about it. For patients with respiratory diseases, residing at moderate altitudes implies increased hypoxemia and clinical deterioration, unless supplementary oxygen is prescribed or patients move to sea level. Hyperventilation increases exposure of residents to air pollutants compared to those living in cities with similar concentrations of pollutants, although at sea level. Humans evolved at sea level and lack the best-known adaptations to reside at moderate or high altitudes. Residents of moderate altitudes breathe deeply the city´s air with all its pollutants, and more often require supplementary oxygen.

Relationship Between Orthostatic Stress Response And Acute Mountain Sickness Susceptibility At High Altitude: Pilot Study

PURPOSE: To determine whether there is a difference in hemodynamic responses to head-up tilt (HUT) in subjects who do, and do not, experience acute mountain sickness (AMS) during exposure to hypobaric hypoxia. We also aimed to determine if those hemodynamic variables altered during HUT correlated with AMS severity. METHODS: Fifteen participants completed three testing sessions: 1) VO2max test to determine workload at 50% VO2max for hypoxia exposure; 2) HUT test consisted of supine rest for 20 min followed by 70° upright tilt for ≤40 min; and 3) six hours of hypobaric hypoxic exposure simulating 4572 m where participants performed two, 30-min cycling bouts and rested when not exercising. During HUT, continuous blood pressure (BP) monitoring was used to assess systolic and diastolic blood pressure (SBP, DBP); mean arterial pressure (MAP); variability in SBP, DBP, and MAP; and heart rate. AMS scores were reported before and after six hours of hypoxic exposure. Statistical analysis included mixed effects ANOVA to determine changes between supine rest and end of HUT and those who scored a ≥ 3 AMS positive (AMS+) and < 3 AMS negative (AMS-) groups. Correlations by linear regression determined associations between HUT hemodynamic responses and AMS scores. Statistical significance was set to p < 0.05. RESULTS: Systolic, diastolic, and mean arterial blood pressure variability (BPV) increased from supine rest to end of HUT (BPV mean difference ± SD for AMS+ & AMS- groups: SBP = 3.5 ± 3.0, 1.2 ± 1.9: DBP = 1.7 ± 1.5, 0.6 ± 0.9: MAP = 2.8 ± 2.9, 1.1 ± 1.4; p = 0.004, 0.004, & 0.006, respectively). Those with higher AMS scores tended to have a greater magnitude of change in SBP, DBP, and MAP variability during the HUT test (r = 0.65, 0.64, & 0.60, respectively). CONCLUSIONS: Increased BPV indicates BP dysregulation, suggesting that AMS+ individuals may have greater disruptions in BP control that could be observable during a postural change prior to hypoxic exposure. BPV during HUT may be a promising predictive variable for AMS but further research is needed. In the future, researchers should consider using sea-level residents and a range of simulated elevations to determine the predictability of AMS susceptibility by BPV.

P 61. Effects of acute normobaric hypoxia on memory and attention in young adults

Objective. An increasing number of sea-level residents takes part in alpine sports such as trekking or skiing. This has inspired a growing research interest on the effects of high altitude and hypoxic conditions on cognition. The aim of this study was to assess the effects of an acute normobaric hypoxia intervention (90 minutes) on cognition in healthy young adults. Methods . Twenty-five healthy, high-altitude-naive adults (25,8 ± 3,3 years; 15 females) were analysed in a randomized cross-over study. Participants received one acute normobaric hypoxic and one normobaric normoxic intervention separated by at least 2 weeks. Heart frequency and saturation of arterial blood oxygenation (SaO2) were continuously monitored while participants lay down for 120 minutes. After 30 minutes, either normobaric hypoxia (SaO2 of 80-85%) or normobaric normoxia was applied for the following 90 minutes. Cognitive parameters related to working memory and sustained attention (d2-Test, N-Back and Digit Span Test) were collected before and after each intervention session. Results . Normobaric hypoxia led to a significant decrease of SaO2 compared to normobaric normoxia (82,7 ± 4,3% vs. 98,1 ± 0,5%, p < .001). Regarding cognitive parameters, no significant time × group interactions were observed. Post hoc t-tests revealed a significant improvement in the d2-Test in both groups. Conclusion . In contrast to previous studies (Malle et al., 2013; Pilmanis, Balldin & Fischer, 2016; Ochi et al., 2018) our results indicate that acute normobaric hypoxia has no effects on working memory and sustained attention. One potential explanation for the absence of effects is the short duration and/or the rather high O2 concentration of the hypoxic condition. In this regard, Ochi et al. have found dose-dependent effects of hypoxia on cognition with the most pronounced results under the severe condition (5000 m). Future studies are needed that investigate dose-response mechanisms of acute hypoxia on cognition.

Altitude Cardiomyopathy Is Associated With Impaired Stress Electrocardiogram and Increased Circulating Inflammation Makers

Many sea-level residents suffer from acute mountain sickness (AMS) when first visiting altitudes above 4,000 m. Exercise tolerance also decreases as altitude increases. We observed exercise capacity at sea level and under a simulated hypobaric hypoxia condition (SHHC) to explore whether the response to exercise intensity represented by physiological variables could predict AMS development in young men. Eighty young men from a military academy underwent a standard treadmill exercise test (TET) and biochemical blood test at sea level, SHHC, and 4,000-m altitude, sequentially, between December 2015 and March 2016. Exercise-related variables and 12-lead electrocardiogram parameters were obtained. Exercise intensity and AMS development were investigated. After exposure to high altitude, the count of white blood cells, alkaline phosphatase and serum albumin were increased (P < 0.05). There were no significant differences in exercise time and metabolic equivalents (METs) between SHHC and high-altitude exposures (7.05 ± 1.02 vs. 7.22 ± 0.96 min, P = 0.235; 9.62 ± 1.11 vs. 9.38 ± 1.12, P = 0.126, respectively). However, these variables were relatively higher at sea level (8.03 ± 0.24 min, P < 0.01; 10.05 ± 0.31, P < 0.01, respectively). Thus, subjects displayed an equivalent exercise tolerance upon acute exposure to high altitude and to SHHC. The trends of cardiovascular hemodynamics during exercise under the three different conditions were similar. However, both systolic blood pressure and the rate–pressure product at every TET stage were higher at high altitude and under the SHHC than at sea level. After acute exposure to high altitude, 19 (23.8%) subjects developed AMS. Multivariate logistic regression analysis showed that METs under the SHHC {odds ratio (OR) 0.355 per unit increment [95% confidence intervals (CI) 0.159−0.793], P = 0.011}, diastolic blood pressure (DBP) at rest under SHHC [OR 0.893 per mmHg (95%CI 0.805−0.991), P = 0.030], and recovery DBP 3 min after exercise at sea level [OR 1.179 per mmHg (95%CI 1.043−1.333), P = 0.008] were independently associated with AMS. The predictive model had an area under the receiver operating characteristic curve of 0.886 (95%CI 0.803−0.969, P < 0.001). Thus, young men have similar exercise tolerance in acute exposure to high altitude and to SHHC. Moreover, AMS can be predicted with superior accuracy using characteristics easily obtainable with TET.

Is Normobaric Hypoxia Effective For Sustaining Previously Acquired Altitude Acclimatization-induced Improvements In Mood State?

PURPOSE: Mood state has been shown to improve with high altitude (HA) acclimatization to 4300 m. The purpose of this study was to determine if these acclimatization effects on mood state persist during reintroduction to 4300 m altitude (RA) after 12 days at sea level (SL) and whether or not normobaric hypoxia (NH) treatment is an effective countermeasure to prevent de-acclimatization. METHODS: Seventeen SL residents (age= 22 ± 6 yr, weight= 75.2 ± 13.3 kg; mean ± SD) completed in the following order: 1) 4 days of baseline SL testing; 2) 12 days of HA acclimatization at 4300 m; 3) 12 days at SL post-HA acclimatization where each received either NH (n=9, FiO2=0.122) or Sham treatment (n=8; FiO2=0.207); and 4) 24-hour reintroduction to 4300 m altitude (RA) in a hypobaric chamber (460 Torr). Mood state was assessed using the Automated Neuropsychological Assessment Metrics Mood Scale (ANAM-MS), which includes the measurement of 7 mood dimensions: vigor, restlessness, depression, anger, fatigue, anxiety and happiness. The test was administered in the afternoon (~2-3pm) on 5 occasions at SL, once after 2h at HA (HA1), 20h at HA (HA2), 11 days at HA exposure (HA11), and following 4 h of RA (RA4). RESULTS: As there were no group differences between NH and Sham mood test scores at any of the time points, data were combined. Fatigue increased (P<0.05) from SL (0.44 ± 0.58) to HA1 (1.16 ± 1.17) and HA2 (1.93 ± 1.26) and then decreased (P<0.05) from HA2 to HA11 (0.67 ± 0.78) and remained low at RA4 (0.58 ± 0.72). Vigor decreased (P<0.05) from SL (2.80 ± 1.42) to HA1 (1.54 ± 1.19) and HA2 (1.33 ± 1.31), and then remained unchanged (P>0.05) from HA2 to HA11 (1.46 ± 1.58), and this effect persisted at RA4 (1.33 ± 1.05). Anxiety increased (P<0.05) from SL (0.17 ± 0.31) to HA1 (0.49 ± 0.97), decreased (P<0.05) from HA1 to HA2 (0.07 ± 0.17), remained unchanged from HA2 to HA11 (0.19 ± 0.60), and remained low at RA4 (0.14 ± 0.30). All other mood states remained unchanged from SL to HA and then RA. CONCLUSION: These results suggest that HA-induced improvements in mood state are retained during RA after 12 days at SL whether or not NH treatment is utilized. Authors’ view not official US Army or DOD policy. Funding USAMRDC.

Short-Term Intermittent Hypoxic Resistance Training Does Not Impair Osteogenic Response in Sea Level Residents.

Background: Osteogenic responses induced by training under hypoxia remain unclear. We aimed to investigate whether intermittent hypoxic resistance training affects osteogenic responses. Materials and Methods: Sixteen male participants underwent resistance training under normoxia (NRT; n = 7) or hypoxia (HRT; O2 = 14.4%, n = 9), twice a week for 8 weeks. The HRT group exercised and rested for 30 minutes under hypoxia, with total hypoxic exposure time in one session of ∼60 minutes. At pre- and postexperiment, bone mineral density (BMD) of the whole body and right proximal femur was measured. At the first and last training sessions, bone alkaline phosphatase (BAP), osteocalcin (OC), cross-linked N-telopeptide of type I collagen (NTx), type I collagen cross-linked C-telopeptide (ICTP), interleukin-6 (IL-6), and blood lactate (La) concentration were analyzed at rest and postexercise. Results: BMD did not change with training and hypoxia. Although BAP, OC, and ICTP levels at rest significantly increased with training (p < 0.01, 0.05, and 0.05, respectively), they did not change with hypoxia. NTx and IL-6 did not change. Additionally, changing patterns of bone markers and La induced by a single bout of exercise were similar among groups in both training sessions. Conclusions: Short-term resistance training enhanced overall bone metabolism, regardless of the oxygen level. Hypoxia has no effects on osteogenic responses.

Intermittent Hypoxia/Hyperoxia Versus Intermittent Hypoxia/Normoxia: Comparative Study in Prediabetes.

Background: Intermittent hypoxia/normoxia training (IHT) is considered a possible means to alleviate chronic diseases such as diabetes. In the last decade, another method of intermittent hypoxia/hyperoxia training (IHHT) began to enter the clinical practice, when the periods of breathing with atmospheric air are replaced by breathing a hyperoxic mixture. The present study compared the impact of adaptation to IHHT versus IHT on some metabolic variables in prediabetic patients. Methods: A placebo-controlled trial included 55 patients with prediabetes, sea level residents, ages 51-74 years. Control Group (16 patients) took sham 3-week course, and the IHHT Group (17 patients) and IHT Group (22 patients) received similar actual sessions of IHHT or IHT five times a week for 3 weeks, each session consisting four cycles of 5 minutes of hypoxia (12% O2) followed by 3 minutes of hyperoxia (IHHT, 33% O2) or 5 minutes of normoxia (IHT, breathing room air). Fasting glucose, oral glucose tolerance test (OGTT), blood lipids, and the level of blood oxygen saturation (SpO2) were investigated at baseline, as well as 1 day and 1 month after IHHT/IHT termination. Results: The study showed the same positive effect of two types of training: equal reduction of serum glucose concentrations, both fasting and 2 hours of OGTT; decreased total blood cholesterol and low-density lipoproteins; and an equally smaller drop in SpO2 during acute hypoxic test (breathing with 12% O2 for 20 minutes). Improved parameters persisted 1 month after training termination in both groups. Conclusion: One of the advantages of IHHT over IHT observed in this study could be some reduction in the duration of the sessions due to shortening reoxygenation periods. Further studies are required to search for additional beneficial effects of IHHT when using other training modes or other pathologies.

Pregnancy outcomes at high-altitude regions in Saudi Arabia; a retrospective study

Background: High altitude associated with chronic hypoxia affects 140 million individuals in the world living at 8,000 feet or higher. This study was aimed at determining the outcomes of pregnancy at high-altitude regions compared to the regions at the sea level. Methodology: A retrospective study was conducted in King Abdulaziz Special Hospital in Taif region and Maternity and Children\&amp;apos;s Hospital at Jeddah between 2012 and 2015. A total of 658 pregnant women and their newborns were enrolled; 329 pregnant women and their newborns living at high-altitude area (from Taif city) and 329 living at sea level area (Jeddah city). Data were analyzed using Statistical Package for the Social Sciences version 16.0. Chi-Square tests were performed to compare the different categorical parameters. Results: Gestational Diabetes Mellitus was found significantly increased (p = 0.006) in pregnant women residing at high altitude (3.01%) compared to those at sea level (0.3%). Mode of delivery was significantly different (p &amp;lt; 0.001) between high altitude and sea level, as 81.76% reported spontaneous vaginal delivery (SVD), 15.2% lower segment caesarean section (LSCS), 0.30% breech presentation (BP), and 2.74% vacuum extraction (VE) at high altitude compared to 60.49% SVD, 38.91% LSCS, 0.61% BP, and 0% VE, respectively, at sea-level residents. Gestational age was significantly higher (p &amp;lt; 0.001) in high altitude (38.14 ± 2.47 weeks) compared to sea level (37.46 ± 29 weeks). Term birth was significantly higher (p = 0.002) in high altitude, as 13.98% at high altitude showed preterm birth compared to 23.1% at sea level. Apgar Score 1 was significantly less frequently reported (p &amp;lt; 0.05) at high altitude residents (7.7 ± 1.4) compared to the sea level (9.47 ± 1.72) residents. Conclusion: The study findings concluded that babies born to sea level residents was healthier compared to those residing at high altitudes. Therefore, more health care is warranted during the delivery of high-altitude residents.

Altitude Acclimatization Alleviates the Hypoxia-Induced Suppression of Exogenous Glucose Oxidation During Steady-State Aerobic Exercise.

This study investigated how high-altitude (HA, 4300 m) acclimatization affected exogenous glucose oxidation during aerobic exercise. Sea-level (SL) residents (n = 14 men) performed 80-min, metabolically matched exercise (O2 ∼ 1.7 L/min) at SL and at HA < 5 h after arrival (acute HA, AHA) and following 22-d of HA acclimatization (chronic HA, CHA). During HA acclimatization, participants sustained a controlled negative energy balance (-40%) to simulate the “real world” conditions that lowlanders typically experience during HA sojourns. During exercise, participants consumed carbohydrate (CHO, n = 8, 65.25 g fructose + 79.75 g glucose, 1.8 g carbohydrate/min) or placebo (PLA, n = 6). Total carbohydrate oxidation was determined by indirect calorimetry and exogenous glucose oxidation by tracer technique with 13C. Participants lost (P ≤ 0.05, mean ± SD) 7.9 ± 1.9 kg body mass during the HA acclimatization and energy deficit period. In CHO, total exogenous glucose oxidized during the final 40 min of exercise was lower (P < 0.01) at AHA (7.4 ± 3.7 g) than SL (15.3 ± 2.2 g) and CHA (12.4 ± 2.3 g), but there were no differences between SL and CHA. Blood glucose and insulin increased (P ≤ 0.05) during the first 20 min of exercise in CHO, but not PLA. In CHO, glucose declined to pre-exercise concentrations as exercise continued at SL, but remained elevated (P ≤ 0.05) throughout exercise at AHA and CHA. Insulin increased during exercise in CHO, but the increase was greater (P ≤ 0.05) at AHA than at SL and CHA, which did not differ. Thus, while acute hypoxia suppressed exogenous glucose oxidation during steady-state aerobic exercise, that hypoxic suppression is alleviated following altitude acclimatization and concomitant negative energy balance.

AltitudeOmics: Baroreflex Sensitivity During Acclimatization to 5,260 m.

Introduction: Baroreflex sensitivity (BRS) is essential to ensure rapid adjustment to variations in blood pressure (BP). Little is known concerning the adaptive responses of BRS during acclimatization to high altitude at rest and during exercise.Methods: Twenty-one healthy sea-level residents were tested near sea level (SL, 130 m), the 1st (ALT1) and 16th day (ALT16) at 5,260 m using radial artery catheterization. BRS was calculated using the sequence method (direct interpretation of causal link between BP and heartrate). At rest, subjects breathed a hyperoxic mixture (250 mmHg O2, end tidal) to isolate the preponderance of CO2 chemoreceptors. End-tidal CO2 varied from 20 to 50 mmHg to assess peripheral chemoreflex. Rebreathing provoked incremental increase in CO2, increasing BP to assess baroreflex. During incremental cycling exercise to exhaustion, subjects breathed room air.Results: Resting BRS decreased in ALT1 which was exacerbated in ALT16. This decrease in ALT1 was reversible upon additional inspired CO2, but not in ALT16. BRS decrease during exercise was greater and occurred at lower workloads in ALT1 compared to SL. At ALT16, this decrease returned toward SL values.Discussion/Conclusion: This study is the first to report attenuated BRS in acute hypoxia, exacerbated in chronic hypoxia. In ALT1, hypocapnia triggered BRS reduction whilst in ALT16 resetting of chemoreceptor triggered BRS reduction. The exercise BRS resetting was impaired in ALT1 but normalized in ALT16. These BRS decreases indicate decreased control of BP and may explain deteriorations of cardiovascular status during exposure to high altitude.

Differential responses of autonomic function in sea level residents, acclimatized lowlanders at >3500 m and Himalayan high altitude natives at >3500 m: A cross-sectional study

We studied the differential responses of autonomic function in sea level residents (SLR), acclimatized lowlanders (ALH) in high altitude (HA) and HA natives (HAN) at >3500 m. Out of 771 male volunteers included in this cross-sectional study, SLR, ALH and HAN groups were comprised of 351, 307 and 113 volunteers, respectively. Our results showed persistent sympathetic dominance with significantly reduced (p < 0.05) parasympathetic response in ALH as compared to SLR and HAN populations. This may be attributed to significantly increased (p < 0.05) concentration of coronary risk factors and plasma catecholamines in ALH as compared to SLR and HAN. The ALH also showed significantly increased (p < 0.05) level of serum homocysteine as compared to SLR. The HAN exhibited no changes in autonomic function despite significantly elevated (p < 0.05) homocysteine level as compared to SLR. Our findings may have clinical relevance for assessment of susceptibility to cardiovascular risks in HA dwellers, native highlanders and patients with hypoxemia.