An increasing number of persons, exposed to high altitude for leisure, sport, or work, may suffer from severe high-altitude illness.
To assess, in a large cohort of subjects, the association between ...physiological parameters and the risk of altitude illness and their discrimination ability in a risk prediction model.
A total of 1,326 persons went through a hypoxic exercise test before a sojourn above 4,000 m. They were then monitored up at high altitude and classified as suffering from severe high-altitude illness (SHAI) or not. Analysis was stratified according to acetazolamide use.
Severe acute mountain sickness occurred in 314 (23.7%), high-altitude pulmonary edema in 22 (1.7%), and high-altitude cerebral edema in 13 (0.98%) patients. Among nonacetazolamide users (n = 917), main factors independently associated with SHAI were previous history of SHAI (adjusted odds ratios aOR, 12.82; 95% confidence interval CI, 6.95-23.66; P < 0.001), ascent greater than 400 m/day (aOR, 5.89; 95% CI, 3.78-9.16; P < 0.001), history of migraine (aOR, 2.28; 95% CI, 1.28-4.07; P = 0.005), ventilatory response to hypoxia at exercise less than 0.78 L/minute/kg (aOR, 6.68; 95% CI, 3.83-11.63; P < 0.001), and desaturation at exercise in hypoxia equal to or greater than 22% (aOR, 2.50; 95% CI, 1.52-4.11; P < 0.001). The last two parameters improved substantially the discrimination ability of the multivariate prediction model (C-statistic rose from 0.81 to 0.88; P < 0.001). Preventive use of acetazolamide reduced the relative risk of SHAI by 44%.
In a large population of altitude visitors, chemosensitivity parameters (high desaturation and low ventilatory response to hypoxia at exercise) were independent predictors of severe high-altitude illness. They improved the discrimination ability of a risk prediction model.
In response to hypobaric hypoxia (HH), which occurs at high altitude, the brain undergoes deleterious changes at the structural and metabolite level. In vivo T sub(2) weighted imaging (T2WI) and ...super(1)H-MRS was performed to understand the structural and metabolic changes in the hippocampus region of rat brain. Data were acquired pre-exposure (baseline controls), immediately after exposure and subsequently at the first, fourth, seventh and 14th days post exposure at normoxia. T sub(2) weighted images of rat brain showed hyperintensity in the CA2/CA3 region of the hippocampus 7 d after acute HH, which persisted till 14 d, probably indicating structural changes in the hippocampus. super(1)H-MRS results showed no change in metabolite level immediately after acute HH exposure, but on the first day of normoxia the myo-inositol level was significantly decreased, possibly due to altered astrocyte metabolism. Metabolic alterations showing an increase in choline and decrease in glutamate on the fourth day of normoxia may be seen as a process of demyelination and loss of glutamate pool respectively. On the seventh and 14th days of normoxia, decreases in N-acetylaspartate, creatine and glutamine+glutamate were observed, which might be due to decreased viability of glutamatergic neurons. In vivo super(1)H-MRS demonstrated early neurometabolic changes prior to probable structural changes post acute HH exposure. The extension of these studies will help in early risk assessment, developing intervention and strategies for combating HH related changes. Copyright copyright 2014 John Wiley & Sons, Ltd. In vivo T2WI and super(1)H-MRS reveal the structural and metabolic changes in the hippocampus region of rat brain post acute hypobaric hypoxic (HH) exposure of 48h. The up- and down-regulation of various metabolites such as myo-inositol, N-acetyl aspartate, creatine and glutamine+glutamate indicates altered astrocyte cellular metabolism, demyelination, neuronal loss and degenerative changes in the brain. These studies will be helpful in early prediction of pathology, which will help in the development of new neuroprotective drugs for combating HH induced changes.
The key elements in acclimatization aim at securing the oxygen supply to tissues and organs of the body with an optimal oxygen tension of the arterial blood. In acute exposure, ventilation and heart ...rate are elevated with a minimum reduction in stroke volume. In addition, plasma volume is reduced over 24–48 h to improve the oxygen‐carrying capacity of the blood, and is further improved during a prolonged sojourn at altitude through an enhanced erythropoiesis and larger Hb mass, allowing for a partial or full restoration of the blood volume and arterial oxygen content. Most of these adaptations are observed from quite low altitudes ∼1000 m above sea level (m a.s.l.) and become prominent from 2000 m a.s.l. At these higher altitudes additional adaptations occur, one being a reduction in the maximal heart rate response and consequently a lower peak cardiac output. Thus, in spite of a normalization of the arterial oxygen content after 4 or more weeks at altitude, the peak oxygen uptake reached after a long acclimatization period is essentially unaltered compared with acute exposure. What is gained is a more complete oxygenation of the blood in the lungs, i.e. SaO2 is increased. The alteration at the muscle level at altitude is minor and so is the effect on the metabolism, although it is debated whether a possible reduction in blood lactate accumulation occurs during exercise at altitude. Transient acute mountain sickness (headache, anorexia, and nausea) is present in 10–30% of subjects at altitudes between 2500 and 3000 m a.s.l. Pulmonary edema is rarely seen below 3000 m a.s.l. and brain edema is not seen below 4000 m a.s.l. It is possible to travel to altitudes of 2500–3000 m a.s.l., wait for 2 days, and then gradually start to train. At higher altitudes, one should consider a staged ascent (average ascent rate 300 m/day above 2000 m a.s.l.), primarily in order to sleep and feel well, and minimize the risk of mountain sickness. A new classification of altitude levels based on the effects on performance and well‐being is proposed and an overview given over the various modalities using hypoxia and altitude for improvement of performance.
Remote ischemic preconditioning (RIPC) has been shown to protect remote organs, such as the brain and the lung, from damage induced by subsequent hypoxia or ischemia. Acute mountain sickness (AMS) is ...a syndrome of nonspecific neurologic symptoms and in high-altitude pulmonary edema excessive hypoxic pulmonary vasoconstriction (HPV) plays a pivotal role. We hypothesized that RIPC protects the brain from AMS and attenuates the magnitude of HPV after rapid ascent to 3,450 m. Forty nonacclimatized volunteers were randomized into two groups. At low altitude (750 m) the RIPC group (
= 20) underwent 4 × 5 min of lower-limb ischemia (induced by inflation of bilateral thigh cuffs to 200 mmHg) followed by 5 min of reperfusion. The control group (
= 20) underwent a sham protocol (4 × 5 min of bilateral thigh cuff inflation to 20 mmHg). Thereafter, participants ascended to 3,450 m by train over 2 h and stayed there for 48 h. AMS was evaluated by the Lake Louise score (LLS) and the AMS-C score. Systolic pulmonary artery pressure (SPAP) was assessed by transthoracic Doppler echocardiography. RIPC had no effect on the overall incidence (RIPC: 35%, control: 35%,
= 1.0) and severity (RIPC vs.
= 0.496 for LLS;
= 0.320 for AMS-C score) of AMS. RIPC also had no significant effect on SPAP maximum after 10 h at high altitude; RIPC: 33 (SD 8) mmHg; controls: 37 (SD 7) mmHg;
= 0.19. This study indicates that RIPC, performed immediately before passive ascent to 3,450 m, does not attenuate AMS and the magnitude of high-altitude pulmonary hypertension.
Remote ischemic preconditioning (RIPC) has been reported to improve neurologic and pulmonary outcome following an acute ischemic or hypoxic insult, yet the effect of RIPC for protecting from high-altitude diseases remains to be determined. The present study shows that RIPC, performed immediately before passive ascent to 3,450 m, does not attenuate acute mountain sickness and the degree of high-altitude pulmonary hypertension. Therefore, RIPC cannot be recommended for prevention of high-altitude diseases.
To provide guidance to clinicians about best preventive and therapeutic practices, the Wilderness Medical Society (WMS) convened an expert panel to develop evidence-based guidelines for prevention ...and treatment of acute mountain sickness, high altitude cerebral edema, and high altitude pulmonary edema. Recommendations are graded based on the quality of supporting evidence and the balance between the benefits and risks/burdens according to criteria put forth by the American College of Chest Physicians. The guidelines also provide suggested approaches to prevention and management of each form of acute altitude illness that incorporate these recommendations. This is an updated version of the original WMS Consensus Guidelines for the Prevention and Treatment of Acute Altitude Illness published in 2010 and subsequently updated as the WMS Practice Guidelines for the Prevention and Treatment of Acute Altitude Illness in 2014.
In contrast to Andean natives, high-altitude Tibetans present with a lower hemoglobin concentration that correlates with reproductive success and exercise capacity. Decades of physiological and ...genomic research have assumed that the lower hemoglobin concentration in Himalayan natives results from a blunted erythropoietic response to hypoxia (i.e., no increase in total hemoglobin mass). In contrast, herein we test the hypothesis that the lower hemoglobin concentration is the result of greater plasma volume, rather than an absence of increased hemoglobin production. We assessed hemoglobin mass, plasma volume and blood volume in lowlanders at sea level, lowlanders acclimatized to high altitude, Himalayan Sherpa, and Andean Quechua, and explored the functional relevance of volumetric hematological measures to exercise capacity. Hemoglobin mass was highest in Andeans, but also was elevated in Sherpa compared with lowlanders. Sherpa demonstrated a larger plasma volume than Andeans, resulting in a comparable total blood volume at a lower hemoglobin concentration. Hemoglobin mass was positively related to exercise capacity in lowlanders at sea level and in Sherpa at high altitude, but not in Andean natives. Collectively, our findings demonstrate a unique adaptation in Sherpa that reorientates attention away from hemoglobin concentration and toward a paradigm where hemoglobin mass and plasma volume may represent phenotypes with adaptive significance at high altitude.
High-altitude adaptation of Tibetans represents a remarkable case of natural selection during recent human evolution. Previous genome-wide scans found many non-coding variants under selection, ...suggesting a pressing need to understand the functional role of non-coding regulatory elements (REs). Here, we generate time courses of paired ATAC-seq and RNA-seq data on cultured HUVECs under hypoxic and normoxic conditions. We further develop a variant interpretation methodology (vPECA) to identify active selected REs (ASREs) and associated regulatory network. We discover three causal SNPs of EPAS1, the key adaptive gene for Tibetans. These SNPs decrease the accessibility of ASREs with weakened binding strength of relevant TFs, and cooperatively down-regulate EPAS1 expression. We further construct the downstream network of EPAS1, elucidating its roles in hypoxic response and angiogenesis. Collectively, we provide a systematic approach to interpret phenotype-associated noncoding variants in proper cell types and relevant dynamic conditions, to model their impact on gene regulation.
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