Endocrine aspects of high altitude acclimatization and acute mountain sickness

The acute acclimatization to high altitude is underpinned by a diuresis (and to a lesser extent a natriuresis) that facilitates a reduction in plasma volume. This allows a haemoconcentration to occur that increases the oxygen carrying capacity of a given volume of blood, a vital effect in the presence of a reduced partial pressure of oxygen. This critical acclimatization process is orchestrated by the endocrine system. This review will present the key evidence regarding the changes in several important hormones that affect this process.     

急进高原新兵对高原及急性高原病的认知调查及防病建议

目的 调查新兵对高原地理及急性高原病（AHAD）认知情况,为降低新兵AHAD发病率、提高高原适应能力和作战能力提供建议和参考.方法 对急进海拔3650 m高原地区的280名新兵进行平原及高原跟踪问卷调查,并对结果进行分析.结果 新兵对高原地理及AHAD的认知率普遍较差,只有18.92%的新兵了解,71.79%的新兵渴望了解.结论 应该采取多种措施,加强对新兵高原地理及AHAD的认知教育.     

Severe acute mountain sickness and suspect high altitude cerebral edema related to nitroglycerin use

An elite mountaineer reported severe acute mountain sickness and ataxia during an 8000-m expedition and concomitant use of transdermal nitroglycerin patches aimed to prevent frostbites. Use of nitroglycerin for this purpose is off-label, and its safety has not been assessed. Moreover, a relation between nitrate-induced cerebral vasodilation and high altitude cerebral edema is theoretically possible on a pathophysiological basis. It is our opinion that nitroglycerin use at high altitude should be discouraged, as efficacy in the prevention of frostbites is questionable and safety has not been assessed.     

The Environmental Symptoms Questionnaire in acute mountain sickness

A self-completed questionnaire (modified Environmental Symptoms Questionnaire) was evaluated in a study of acute mountain sickness (AMS). The questionnaire scores for headache, nausea, and the general feeling of ill health correlated well with AMS scores obtained by clinical interview. Modifications in the instructions and the phrasing of some of the questions are suggested and we doubt whether factor analysis provides any better data than more simple statistical methods. The questionnaire is a useful additional method for the assessment of symptoms of AMS.     

Cognitive changes at high altitude in healthy climbers and in climbers developing acute mountain sickness

We report the cognitive functions of 17 non-acclimatized mountaineers who ascended from low lands to an altitude of 4,559 m in 24 h and were studied there within 6 h. We found that this rapid ascent to high altitude had small, but differential effects upon cognitive performance depending upon the later development of acute mountain sickness (AMS). Subjects who developed AMS within a 24-48-h stay at high altitude were mildly impaired in short term memory, but improved in conceptual tasks, while subjects who remained healthy had a better short term memory performance but no improvement in cognitive flexibility. Possible explanations for these unexpected effects of high altitude are discussed.     

黄芩苷与红景天胶囊对急性高原病预防作用比较

 目的 探讨黄芩苷胶囊对急性高原病(acute mountain sickness, AMS)的预防作用。方法 采用随机对照的研究方法, 80名急进高原健康男性青年随机分为3组, 黄芩苷组(n=32)、红景天组(n=24)和安慰剂组(n=24)。3组在进入高原前2 d、进入高原后连续3 d分别服用黄芩苷胶囊(0.5 g, 2次/d)、红景天胶囊(0.76 g, 2次/d)和安慰剂(2粒, 2次/d)。检测急进高原前(海拔397 m)和急进高原后(3658 m)受试者氧饱和度、心率、收缩压、舒张压, 彩色多普勒超声测量肺动脉收缩压(pulmonary artery systolic pressure, PASP)和平均肺动脉压(mean pulmonary arterial pressure, MPAP), 统计急进高原后各组的AMS发病率。结果 急进高原后安慰剂组、黄芩苷组和红景天组的AMS发病率分别为58.3%(14/24)、25.0%(8/32)和29.2%(7/24), 与安慰剂组比较, 黄芩苷组及红景天组AMS发病率明显降低, 差异有统计学意义(P<0.05)。与急进高原前比较, 各组受试者急进高原后心率、血压及肺动脉压均升高, 氧饱和度降低(P<0.05);与安慰剂组比较, 黄芩苷组血压及心率明显降低(P<0.05), 红景天组急进高原后氧饱和度升高、肺动脉压降低(P<0.05)。结论 黄芩苷组可能通过降低血压及心率预防AMS的发生, 红景天胶囊可能通过升高氧饱和度, 降低PASP、MPAP预防AMS的发生。     

Ocular functions and incidence of acute mountain sickness in women at altitude

The effects of altitude on a series of ocular functions were studied on seven expedition members, all women aged 23-53 years, during the first ascent of the 6798-m peak Brigupanth in the Indian Himalayas. The only consistent change was a decrease in convergence amplitude. The amplitude of accommodation remained stable among the younger climbers, but decreased markedly among the older ones as higher altitudes were reached. There also appeared to be a lessened vascular reactivity to the hypoxia of altitude in the older members. Stereoscopic vision was unimpaired at all altitudes tested and extra-ocular muscle balance remained unaffected in all but two members who had an increase in their baseline phorias. Two of the summit climbers developed retinal hemorrhages. There was an average weight loss of 5.4 kg during the climb, but general health was good. Symptoms of acute mountain sickness were noted infrequently, and there were only moderate changes in the menstrual cycle.     

Elevated plasma cholecystokinin at high altitude: metabolic implications for the anorexia of acute mountain sickness

The aims of the present study were to measure the satiety neuropeptide cholecystokinin (CCK) in humans at terrestrial high altitude to investigate its possible role in the pathophysiology of anorexia, cachexia, and acute mountain sickness (AMS). Nineteen male mountaineers aged 38 +/- 12 years participated in a 20 +/- 5 day trek to Mt. Kanchenjunga basecamp (BC) located at 5,100 m, where they remained for 7 +/- 5 days. Subjects were examined at rest and during a maximal exercise test at sea-level before/after the expedition (SL1/SL2) and during the BC sojourn. There was a mild increase in Lake Louise AMS score from 1.1 +/- 1.2 points at SL1 to 2.3 +/- 2.3 points by the end of the first day at BC (P < 0.05). A marked increase in resting plasma CCK was observed on the morning of the second day at BC relative to sea-level control values (62.9 +/- 42.2 pmol/L(-1) vs. SL1: 4.3 +/- 8.3 pmol/L(-1), P < 0.05 vs. SL2: 26.5 +/- 25.2 pmol/L(-1), P < 0.05). Maximal exercise increased CCK by 78.5 +/- 24.8 pmol/L(-1), (P < 0.05 vs. resting value) during the SL1 test and increased the plasma concentration of non-esterified fatty acids and glycerol at BC (P < 0.05 vs. SL1/SL2). The CCK response was not different in five subjects who presented with anorexia on Day 2 compared with those with a normal appetite. While there was no relationship between the increase in CCK and AMS score at BC, a more pronounced increase in resting CCK was observed in subjects with AMS (> or =3 points at the end of Day 1 at BC) compared with those without (+98.9 +/- 1.4 pmol/L(-1) vs. +67.6 +/- 37.2 pmol/L(-1), P < 0.05). Caloric intake remained remarkably low during the stay at BC (8.9 +/- 1.4 MJ.d(-1)) despite a progressive decrease in total body mass (-4.5 +/- 2.1 kg after 31 +/- 13 h at BC, P < 0.05 vs. SL1/SL2), which appeared to be due to a selective loss of torso adipose tissue. These findings suggest that the satiogenic effects of CCK may have contributed to the observed caloric deficit and subsequent cachexia at high altitude despite adequate availability of palatable foods. The metabolic implications of elevated CCK in AMS remain to be elucidated.     

Acute mountain sickness in a subject with metabolic syndrome at high altitude

Abstract Strapazzon, Giacomo, Annalisa Cogo, and Andrea Semplicini. Acute mountain sickness in a subject with metabolic syndrome at high altitude. High Alt. Med. Biol. 9:245-248, 2008.-Visitors at high altitude are increasing in age and comorbidities, which can lead to a failure in acclimatization. We describe the development of acute mountain sickness (AMS) in a 44-year-old man with metabolic syndrome and the time- and altitude-dependent correlation between the development of AMS and blood pressure and heart rate changes. Our observations support a dominant role of endothelial dysfunction in the pathogenesis of AMS and suggest new behavioral indications.     

Diurnal variations of acute mountain sickness, colour vision, and plasma cortisol and ACTH at high altitude

Time dependence of colour vision in the green/red axis, signs of acute mountain sickness (AMS), and plasma cortisol and ACTH concentrations were studied in eight sea-level male natives exposed 79 h to altitude hypoxia at 4,350 m. Colour vision (CV) was explored every 2 h from 08:00 to 20:00 hours by means of two portable anomaloscopes, one derived from Essilor CHROMOTEST and the other from the OSCAR. Significant diurnal variations in CV were found using both anomaloscopes, major alterations in green relative to red sensitivity being seen in the early morning. AMS scores also showed remarkable diurnal variations, parallel to those of plasma cortisol and CV, with maximum values observed at 08:00 hours. Cortisol diurnal rhythm was maintained in hypoxia, with mean concentrations higher than in normoxia. ACTH followed the same trend, but variations were not significant. Significant correlations were found between instant values of CV, cortisol, and AMS score, but no causal relationship between these variables can be ascertained.     

Acute mountain sickness; prophylactic benefits of antioxidant vitamin supplementation at high altitude

Acute mountain sickness; prophylactic benefits of Free-radical-mediated damage to the blood-brain barrier may be implicated in the pathophysiology of acute mountain sickness (AMS). To indirectly examine this, we conducted a randomized double-blind placebo-controlled trial to assess the potentially prophylactic benefits of enteral antioxidant vitamin supplementation during ascent to high altitude. Eighteen subjects aged 35 +/- 10 years old were randomly assigned double-blind to either an antioxidant (n = 9) or placebo group (n = 9). The antioxidant group ingested 4 capsules/day(-1) (2 after breakfast/2 after evening meal) that each contained 250 mg of L-ascorbic acid, 100 IU of dl-a-tocopherol acetate and 150 mg of alpha-lipoic acid. The placebo group ingested 4 capsules of identical external appearance, taste, and smell. Supplementation was enforced for 3 weeks at sea level and during a 10-day ascent to Mt. Everest base camp (approximately 5,180 m). Antioxidant supplementation resulted in a comparatively lower Lake Louise AMS score at high altitude relative to the placebo group (2.8 +/- 0.8 points versus 4.0 +/- 0.4 points, P = 0.036), higher resting arterial oxygen saturation (89 +/- 5% versus 85 +/- 5%, P = 0.042), and total caloric intake (13.2 +/- 0.6 MJ/day(-1) versus 10.1 +/- 0.7 MJ/day(-1), P = 0.001); the latter is attributable to a lower satiety rating following a standardized meal. These findings indicate that the exogenous provision of water and lipid-soluble antioxidant vitamins at the prescribed doses is an apparently safe and potentially effective intervention that can attenuate AMS and improve the physiological profile of mountaineers at high altitude.     

急进高原人群肾上腺皮质机能状态与急性高原病的相关性探讨

目的探讨肾上腺皮质激素与急性高原病的关系。方法分别在低海拔区和高海拔区不同时间抽取534名急进高原人群的肘静脉血,放免法检测血浆皮质醇（F）、醛固酮（ALD）、肾素活性（PRA）、血管紧张素Ⅱ（A1I）及睾酮（T）等水平;采用症状评分法评价高原反应程度,分析急进高原人群肾上腺皮质机能状态与急性高原病发病之间的相关关系。结果血浆F、AⅡ含量随海拔增高而增高,PRA下降,以F含量增高最显著,而ALD及T变化不明显;进入高原后,随着时问延长,血浆F、AⅡ和T含量明显下降;实验同时表明,在平原血浆F测定值明显低于正常的人易发生急性高原病。结论急进高原人群的肾上腺皮质激素水平与急性高原病的发病明显相关。     

A Tibetan with chronic mountain sickness followed by high altitude pulmonary edema on reentry

Chronic mountain sickness (CMS) and high altitude pulmonary edema (HAPE) each occur rarely in Tibetans, and they have previously not been reported in the same person. Here we describe a 37-year-old native Tibetan man with CMS at 4300 m, who developed HAPE after his return home from a 12-day visit to sea level. Possible common pathogenetic factors included a poor ventilatory response to hypoxia, accentuated hypoxemia, pulmonary hypertension, and increased blood volume. In addition, strenuous exercise and high levels (to approximately 1000 ng/L) of plasma atrial natriuretic peptide may have contributed to HAPE.     

Statistical models of acute mountain sickness

Acute mountain sickness (AMS) is caused by exposure to altitudes exceeding 2500 m and often resolves by acclimatization without further ascent. Statistical models of AMS score and the probability of an AMS diagnosis were developed to allow the combination of dissimilar exposures for simultaneous analysis. The study population was 302 trekkers from a previous investigation who provided self-reported symptoms upon arrival at 3840 m during hikes through altitudes of 1500 to 6200 m. AMS score (Hackett scale) was estimated by linear regression and the probability of an AMS diagnosis (Lake Louise criteria) by logistic regression. AMS score or probability was significantly associated with exposure day and altitude. Increased altitude over the prior 3 days resulted in higher estimated AMS score or probability and decreased altitude in lower score or probability. The odds ratio (OR) of AMS was 3.6 if not on acetazolamide. Females appeared slightly more susceptible than males (1.5 OR). The approach offers the advantages of (1) improved statistical power by combining exposures, (2) insight into the dose-response relationship of altitude exposure and AMS risk, (3) quantitative tests for the significance of factors that might affect AMS susceptibility, and (4) practical tools to track individual climbers and plan operational ascents.     

Symptoms of infection and acute mountain sickness; associated metabolic sequelae and problems in differential diagnosis

Infections and acute mountain sickness (AMS) are common at high altitude, yet their precise etiologies remain elusive and the potential for differential diagnosis is considerable. The present study was therefore designed to compare clinical nonspecific symptoms associated with these pathologies and basic changes in free radical and amino-acid metabolism. Nineteen males were examined at rest and after maximal exercise at sea level before (SL(1)/SL(2)) and following a 20 +/- 5 day ascent to Kanchenjunga base camp located at 5100 m (HA). Four subjects with symptoms consistent with an ongoing respiratory and recent gastrointestinal infection were also diagnosed with clinical AMS on the evening of day 1 at HA. These and six other subjects recovering from symptoms consistent with a respiratory infection presented with a greater increase (HA minus SL(1)) in AMS scores and resting venous concentration of lipid hydroperoxides (LH) and in total creatine phosphokinase and ratio of free tryptophan/branched chain amino acids, and greater decrease in glutamine (Gln) compared to healthy controls (n = 9, p < 0.05). The decrease in Gln was consistently related to the altitude/exercise-induced increase in LH (r = -0.69/r = -0.45; p < 0.05) and altitude-induced increase in myoglobin (r = -0.73, p < 0.05). These findings highlight the potential for the misdiagnosis of altitude illness due to the similarity of nonspecific constitutional symptoms associated with infection and AMS. Both conditions were characterized by parallel changes in peripheral biomarkers related to free-radical, skeletal muscle damage and amino acid metabolism. While clearly not establishing cause and effect, free radical-mediated changes in peripheral amino acid metabolism known to influence immune and cerebral serotoninergic function may enhance susceptibility to and/or delay recovery from altitude illness.     

Effect of spironolactone on acute mountain sickness

This study examined the effectiveness of spironolactone as a prophylactic agent for the prevention of acute mountain sickness (AMS). Spironolactone, 25 mg PO QID, or placebo was administered to nine subjects in a double-blind, placebo-controlled, crossover design. Medication was given for 48 h prior to and during a 46-h exposure to 427 mm Hg (4570 m) in a hypobaric chamber. Six subjects demonstrated prevention of either the cerebral or respiratory symptoms of AMS during at least one segment of the altitude sojourn.