Karinen, Heikki, Juha E. Peltonen, Mika Kähönen, and Heikki O. Tikkanen. Prediction of acute mountain sickness by monitoring arterial saturation during ascent. High Alt. Med. Biol. 11:325–332, 2010.—Acute mountain sickness (AMS) is a common problem while ascending at high altitude. AMS may progress rapidly to fatal results if the acclimatization process fails or symptoms are neglected and the ascent continues. Extensively reduced arterial oxygen saturation at rest (R-Sp o 2 ) has been proposed as an indicator of inadequate acclimatization and impending AMS. We hypothesized that climbers less likely to develop AMS on further ascent would have higher Sp o 2 immediately after exercise (Ex-Sp o 2 ) at high altitudes than their counterparts and that these postexercise measurements would provide additional value for resting measurements to plan safe ascent. The study was conducted during eight expeditions with 83 ascents. We measured R-Sp o 2 and Ex-Sp o 2 after moderate daily exercise [50 m walking, target heart rate (HR) 150 bpm] at altitudes of 2400 to 5300 m during ascent. The Lake Louise Questionnaire was used in the diagnosis of AMS. Ex-Sp o 2 was lower at all altitudes among those climbers suffering from AMS during the expeditions than among those climbers who did not get AMS at any altitude during the expeditions. Reduced R-Sp o 2 and Ex-Sp o 2 measured at altitudes of 3500 and 4300 m seem to predict impending AMS at altitudes of 4300 m ( p < 0.05 and p < 0.01) and 5300 m (both p < 0.01). Elevated resting HR did not predict impending AMS at these altitudes. Better aerobic capacity, younger age, and higher body mass index (BMI) were also associated with AMS (all p < 0.01). In conclusion, those climbers who successfully maintain their oxygen saturation at rest, especially during exercise, most likely do not develop AMS. The results suggest that daily evaluation of Spo 2 during ascent both at rest and during exercise can help to identify a population that does well at altitude.
MacInnis, Martin J., Michael S. Koehle, and Jim L. Rupert. Evidence for a genetic basis for altitude illness: 2010 update. High Alt. Med. Biol. 11:349–368, 2010.—Altitude illness refers to a group of environmentally mediated pathophysiologies. Many people will suffer acute mountain sickness shortly after rapidly ascending to a moderately hypoxic environment, and an unfortunate few will develop potentially fatal conditions such as high altitude pulmonary edema or high altitude cerebral edema. Some individuals seem to be predisposed to developing altitude illness, suggesting an innate contribution to susceptibility. The implication that there are altitude-sensitive and altitude-tolerant individuals has stimulated much research into the contribution of a genetic background to the efficacy of altitude acclimatization. Although the effect of altitude attained and rate of ascent on the etiology of altitude illness is well known, there are only tantalizing, but rapidly accumulating, clues to the genes that may be involved. In 2006, we reviewed what was then known about the genetics of altitude illness. This article updates that review and attempts to tabulate all the available genetic data pertaining to these conditions. To date, 58 genes have been investigated for a role in altitude illness. Of these, 17 have shown some association with the susceptibility to, or the severity of, these conditions, although in many cases the effect size is small or variable. Caution is recommended when evaluating the genes for which no association was detected, because a number of the investigations reviewed in this article were insufficiently powered to detect small effects. No study has demonstrated a clear-cut altitude illness gene, but the accumulating data are consistent with a polygenic condition with a strong environmental component. The genes that have shown an association affect a variety of biological pathways, suggesting that either multiple systems are involved in altitude pathophysiology or that gene–gene interactions play a role. Although numerous studies have been performed to investigate specific genes, few have looked for evidence of heritability or familial transmission, or for epidemiological patterns that would be consistent with genetically influenced conditions. Future trends, such as genome-wide association studies and epigenetic analysis, should lead to enhanced understanding of the complex interactions within the genome and between the genome and hypoxic environments that contribute to an individual's capacity to acclimatize rapidly and effectively to altitude.
Muza, Stephen R., Beth A. Beidleman, and Charles S Fuco. Altitude preexposure recommendations for inducing acclimatization. High Alt. Med.Biol. 11:87-92, 2010.-For many low-altitude ( 2400 m) altitudes without having the time to develop an adequate degree of altitude acclimatization. Prior to departing on these trips, low-altitude residents can induce some degree of altitude acclimatization by ascending to moderate (> 1500 m) or high altitudes during either continuous or intermittent altitude preexposures. Generally, the degree of altitude acclimatization developed is proportional to the altitude attained and the duration of exposure. The available evidence suggests that continuous residence at 2200m or higher for 1 to 2 days or daily 1.5- to 4-h exposures to > 4000m induce ventilatory acclimatization. Six days at 2200m substantially decreases acute mountain sickness (AMS) and improves work performance after rapid ascent to 4300 m. There is evidence that 5 or more days above 3000m within the last 2 months will significantly decrease AMS during a subsequent rapid ascent to 4500 m. Exercise training during the altitude preexposures may augment improvement in physical performance. The persistence of altitude acclimatization after return to low altitude appears to be proportional to the degree of acclimatization developed. The subsequent ascent to high altitude should be scheduled as soon as possible after the last altitude preexposure.
Stewart J. Jackson, James Varley, Claudia Sellers, Katherine Josephs, Lucy Codrington, Georgina Duke, Marina A. Njelekela Gordon Drummond, Andrew I. Sutherland, A. A. Roger Thompson, J. Kenneth Baillie. Incidence and predictors of acute mountain sickness among trekkers on Mount Kilimanjaro. High Alt. Med. Biol. 217-222, 2010-. We investigated the incidence of AMS amongst a general population of trekkers on Mount Kilimanjaro, using the Lake Louise consensus scoring system (LLS). Additionally we examined the effect of prophylactic acetazolamide and different ascent profiles. Climbers on 3 different ascent itineraries were recruited. At 2743m we recruited 177 participants (mean age 31, range [18-71]) who completed LLS together with an epidemiological questionnaire. At 4730m participants (n = 189, male = 108, female = 68, mean age 33, range ) completed LLS, 136 of whom had been followed up from 2730 m. At 2743 m, 3% (5/177) of climbers were AMS positive, and 47% (89/189) of climbers from all itineraries were AMS positive at 4730m. Of climbers attempting the Marangu itineraries, 33% (45/136) were taking acetazolamide. This group had a similar rate of AMS and no statistical difference in severity of LLS when compared with those not taking prophylactic drugs. We also did not demonstrate a difference between the incidence of AMS in climbers who did or did not take a rest day at 3700 m. However, there was a significant reduction in the incidence of AMS amongst pre-acclimatized subjects. Consistent with previous work, we found that the rate of AMS on Mount Kilimanjaro is high. Furthermore, at these fast ascent rates, there was no evidence of a protective effect of acetazolamide or a single rest day. There is a need to increase public awareness of the risks of altitude sickness and we advocate a pragmatic "golden rules" approach (http://www.altitude.org/altitude_sickness.php).
Mairer, Klemens, Maria Wille, and Martin Burtscher. The prevalence of and risk factors for acute mountain sickness in the Eastern and Western Alps. High Alt. Med. Biol. 11:343–348 , 2010. — Acute mountain sickness (AMS) is the most common condition of high altitude illnesses. Its prevalence varies between 15% and 80% depending on the speed of ascent, absolute altitude reached, and individual susceptibility. Additionally, we assumed that the more experienced mountaineers of the Western Alps are less susceptible to developing AMS than recreational mountaineers of the Eastern Alps or tourist populations. Therefore, the main goals of the present study were the collection of data regarding the AMS prevalence and triggers in both the Eastern and Western Alps using identical methods. A total of 162 mountaineers, 79 in the Eastern Alps (3454 m) and 83 in the Western Alps (3817 m) were studied on the morning after their first night at high altitude. A diagnosis of AMS was based on a Lake Louise Score (LLS) ≥4, the presence of headache, and at least one additional symptom. Thirty of 79 subjects (38.0%) suffered from AMS at 3454 m in the Eastern Alps as did 29 of 83 (34.9%) at 3817 m in the Western Alps. After adjustment for altitude, the prevalence in the Western Alps constituted 24.5%, which differed significantly ( p = 0.04) from that found in the Eastern Alps. The lower mountaineering experience of mountaineers in the Eastern Alps turned out to be the only factor for explaining their higher AMS prevalence. Thus, expert advice by mountain guides or experienced colleagues could help to reduce the AMS risk in these subjects.
Himadri, P., S. K. S. Sarada, M. Chitharanjan, and S. Dhananjay. Role of oxidative stress and inflammation in hypoxia-induced cerebral edema: a molecular approach. High Alt. Med. Biol. 11:231-244, 2010.-The present study reports the possible role of oxidative stress and inflammation (role of nuclear factor, NFkB) in hypoxia-induced transvascular leakage in brain of rats. The rats were exposed to a simulated altitude of 25,000 ft for different durations: 0, 3, 6, 12, 24, and 48 h. Brain water content, transvascular leakage, oxidative stress, and proinflammatory parameters were studied at different durations of hypoxic exposure. The results revealed that maximum increase in transvascular leakage in brain of rats was observed at 24 h of hypoxic exposure (240.16 +/- 1.95 relative fluorescence units (r.f.u)/g tissue) compared with control (100.58 +/- 1.79 r.f.u/g tissue). There was a significant increase in reactive oxygen species (ROS) and lipid peroxidation (MDA), with concomitant reduction in antioxidants. Hypoxic exposure resulted in a significant increase in NFkB protein expression levels and in the DNA binding activity in the 24-h hypoxic exposure (p < 0.001) compared with control. There was a significant increase in proinflammatory cytokines, with concomitant upregulation of cell adhesion molecules. Simultaneously, to rule out the fact that inflammation causes cerebral edema, the rats were pretreated with curcumin (100mg/kg body weight) 1 h prior to 24-h hypoxia. Curcumin pretreatment significantly attenuated the hypoxia-induced cerebral transvascular leakage (p < 0.05), with concomitant downregulation in the expression of brain NF kappa B levels (p < 0.001). The present study therefore reveals that inflammation (NF kappa B) plays a significant role in hypoxia-induced cerebral edema.
Ren, Yusheng, Zhongming Fu, Weimin Shen, Ping Jiang, Yanlin He, Shaojun Peng, Zonggui Wu, and Bo Cui. Incidence of high altitude illnesses among unacclimatized persons who acutely ascended to Tibet. High Alt. Med. Biol. 11:39–42, 2010.— High altitude illnesses pose health threats to unwary travelers after their acute ascent to high altitude locations. The incidence of high altitude illnesses among unacclimatized persons who acutely ascend to Tibet has not been previously reported. In the present study, we surveyed the incidence of high altitude illness among 3628 unacclimatized persons who had no previous high altitude experience and who traveled to Tibet by air to an altitude of 3600 m. These subjects were asked to answer questions in a written questionnaire about symptoms associated with high altitude illnesses that occurred within 2 weeks of their first arrival, their severity, and possible contributing factors. Physical examination and appropriate laboratory tests were also performed for hospitalized subjects. We found that 2063 respondents had mild acute mountain sickness with an incidence of 57.2%, and 249 (12.07%) of them were hospitalized for treatment. The incidence of high altitude pulmonary edema was 1.9%, while no case of high altitude cerebral edema was found. Additionally, there was no report of death. Psychological stresses and excessive physical exertions possibly contributed to the onset of HAPE. Acute mountain sickness is common among unacclimatized persons after their acute ascent to Tibet. The incidence of HAPE and HACE, however, is very low among them.
Dehnert, Christoph, and Peter Bartsch. Can patients with coronary heart disease go to high altitude? High Alt. Med. Biol. 11:183-187, 2010.-Tourism to high altitude is very popular and includes elderly people with both manifest and subclinical coronary heart disease (CHD). Thus, risk assessment regarding high altitude exposure of patients with CHD is of increasing interest, and individual recommendations are expected despite the lack of sufficient scientific evidence. The major factor increasing cardiac stress is hypoxia. At rest and for a given external workload, myocardial oxygen demand is increased at altitude, particularly in nonacclimatized individuals, and there is some evidence that blood-flow reserve is reduced in atherosclerotic coronary arteries even in the absence of severe stenosis. Despite a possible imbalance between oxygen demand and oxygen delivery, studies on selected patients have shown that exposure and exercise at altitudes of 3000 to 3500m is generally safe for patients with stable CHD and sufficient work capacity. During the first days at altitude, patients with stable angina may develop symptoms of myocardial ischemia at slightly lower heart ratexblood-pressure products. Adverse cardiac events, however, such as unstable angina coronary syndromes, do not occur more frequently compared with sea level except for those who are unaccustomed to exercise. Therefore, training should start before going to altitude, and the altitude-related decrease in exercise capacity should be considered. Travel to 3500m should be avoided unless patients have stable disease, preserved left ventricular function without residual capacity, and above-normal exercise capacity. CHD patients should avoid travel to elevations above 4500m owing to severe hypoxia at these altitudes. The risk assessment of CHD patients at altitude should always consider a possible absence of medical support and that cardiovascular events may turn into disaster.
Kelly, Thomas E., and Peter H. Hackett. Acetazolamide and sulfonamide allergy: a not so simple story. High Alt. Med. Biol. 11:319–323, 2010.—Allergies and adverse reactions to sulfonamide medications are quite common. Two distinct categories of drugs are classified as sulfonamides: antibiotics and nonantibiotics. The two groups differ in their chemical structure, use, and the rate at which adverse reactions occur. Cross-reactivity between the two groups has been implied in the past, but is suspect. Acetazolamide, from the nonantibiotic group, is routinely used in the prevention and treatment of high altitude issues and may not need to be avoided in individuals with a history of sulfonamide allergy. This review addresses the differences between the groups and the propensity for intergroup and intragroup adverse reactions based on the available literature. We also examine the different clinical presentations of allergy and adverse reactions, from simple cutaneous reactions with no sequelae through Stevens–Johnson syndrome and anaphylaxis, with risk for significant morbidity and mortality. We offer a systematic approach to determine whether acetazolamide is a safe option for those with a history of allergy to sulfonamides.
Wu, Tian Yi, Shou Quan Ding, Sheng Lin Zhang, Jin Qing Duan, Bao Yu Li, Zhong Yan Zhan, Qin Li Wu, Suolung Baomu, Bao Zhu Liang, Shu Rang Han, Yu Ling Jie, Gang Li, Lin Sun, and Bengt Kayser. Altitude illness in Qinghai-Tibet railroad passengers. High Alt. Med. Biol. 189-198, 2010.-It takes similar to 24 h to travel the similar to 3000-km-long Qinghai-Tibet railroad of which 85% is situated above 4000m with a pass at 5072m. Each year about 2 million passengers are rapidly exposed to high altitude traveling on this train. The aim of this study was to quantify the occurrence of altitude illness on the train. Three subject groups were surveyed: 160 Han lowlanders, 62 Han immigrants living at 2200 to 2500 m, and 25 Tibetans living at 3700 to 4200 m. Passengers reached 4768m from 2808m in less than 1.5 h, after which 78% of the passengers reported symptoms, 24% reaching the Lake Louise criterion score for AMS. AMS incidence was 31% in nonacclimatized Han compared to 16% in Han altitude residents and 0% in Tibetans. Women and older subjects had a slightly greater risk for AMS. Most cases of AMS were mild and self-limiting, resolving within days upon arrival in Lhasa. Some cases of more severe AMS necessitated medical attention. To curb the health risk of rapid travel to altitude by train, prospective travelers should be better informed, medical train personnel should be well trained, and staged travel with 1 to 2 days at intermediate altitudes should be suggested to nonacclimatized subjects.
Wagner, Peter D. Operation Everest II. High Alt. Med. Biol. 11:111-119, 2010.-In October 1985, 25 years ago, 8 subjects and 27 investigators met at the United States Army Research Institute for Environmental Medicine (USARIEM) altitude chambers in Natick, Massachusetts, to study human responses to a simulated 40-day ascent of Mt. Everest, termed Operation Everest II (OE II). Led by Charlie Houston, John Sutton, and Allen Cymerman, these investigators conducted a large number of investigations across several organ systems as the subjects were gradually decompressed over 40 days to the Everest summit equivalent. There the subjects reached a (V) triple over dot o(2) max of 15.3 mL/kg/min (28% of initial sea-level values) at 100 W and arterial Po-2 and Pco(2) of similar to 28 and similar to 10mm Hg, respectively. Cardiac function resisted hypoxia, but the lungs could not: ventilation-perfusion inequality and O-2 diffusion limitation reduced arterial oxygenation considerably. Pulmonary vascular resistance was increased, was not reversible after short-term hyperoxia, but was reduced during exercise. Skeletal muscle atrophy occurred, but muscle structure and function were otherwise remarkably unaffected. Neurological deficits (cognition and memory) persisted after return to sea level, more so in those with high hypoxic ventilatory responsiveness, with motor function essentially spared. Nine percent body weight loss (despite an unrestricted diet) was mainly (67%) from muscle and exceeded the 2% predicted from energy intake-expenditure balance. Some immunological and lipid metabolic changes occurred, of uncertain mechanism or significance. OE II was unique in the diversity and complexity of studies carried out on a single, courageous cohort of subjects. These studies could never have been carried out in the field, and thus complement studies such as the American Medical Research Expedition to Everest (AMREE) that, although more limited in scope, serve as benchmarks and reality checks for chamber studies like OE II.
Wang, Shih-Hao, Yu-Cheng Chen, Wei-Fong Kao, Yu-Jr Lin, Jih-Chang Chen, Te-Fa Chiu, Tai-Yi Hsu, Hang-Cheng Chen, and Shih-Wei Liu. Epidemiology of acute mountain sickness on Jade Mountain, Taiwan: an annual prospective observational study. High Alt. Med. Biol. 11:43–49, 2010.—Acute mountain sickness (AMS) is a pathophysiological symptom complex that occurs in high altitude areas. The AMS prevalence is reportedly 28% on Jade Mountain, the highest mountain (3952 m) in Taiwan. We conducted this study owing to the lack of annual epidemiological data on AMS in Taiwan. Between April 2007 and March 2008, 1066 questionnaires were completed by trekkers visiting Paiyun Lodge on Jade Mountain. Information in the questionnaire included demographic data, mountaineering experience, AMS history, and trekking schedule. Weather data were obtained from the Central Weather Bureau of Taiwan. The Lake Louise AMS score was used to record symptoms and diagnose AMS. The χ-square test or the Student t test was used to evaluate associations between variables and AMS. In our study, the AMS prevalence was 36%. It increased significantly at different rates at different locations on the Jade Mountain trail and varied significantly in different months. Rainy weather tended to slightly increase the incidence of AMS. A lower incidence of AMS was correlated with hig-altitude trekking experience or preexposure ( p < 0.05), whereas a higher incidence of AMS was correlated with a prior history of AMS ( p < 0.05). The trekkers with AMS were significantly younger, ascended faster from their residence to the entrance or to Paiyun Lodge, and ascended slower from the entrance to the Paiyun Lodge ( p < 0.05), but the differences lacked clinical significance. No differences in the incidence of AMS based on blood type, gender, or obesity were observed. The most common symptom among all trekkers was headache, followed by difficulty sleeping, fatigue or weakness, gastrointestinal (GI) symptoms, and dizziness or lightheadedness. In conclusion, the AMS prevalence on Jade Mountain was 36%, varied by month, and correlated with trekking experience, preexposure, and a prior history of AMS. The overall presentation of AMS was similar to that on other major world mountains.
Schommer, Kai, Neele Wiesegart, Elmar Menold, Ute Haas, Hermann Buhl, Pezter Bärtsch, and Christoph Dehnert. Training in normobaric hypoxia and its effects on acute mountain sickness after rapid ascent to 4559 m. High Alt. Med. Biol. 11:19–25, 2010.—In a randomized, placebo-controlled, double-blind study, we tested a 4-week program in normobaric hypoxia that is commercially offered for the prevention of acute mountain sickness (AMS). Twenty-two male and 18 female healthy subjects [mean age 33 ± 7 (SD) years] exercised 70 min, 3x/week for 3 weeks on a bicycle ergometer at workloads of 60% V o 2 max either in normoxia (normoxia group, NG) or in normobaric hypoxia (hypoxia group, HG), corresponding to altitudes of 2500, 3000, and 3500 m during weeks 1, 2, and 3, respectively. Four passive exposures of 90 min in normoxia (NG) or hypoxia corresponding to 4500 m (HG) followed in week 4. Five days after the last session, subjects ascended within 24 h from sea level to 4559 m (one overnight stay at 3611 m) and stayed there for 24 h. AMS was defined as LL (Lake Louise score) ≥5 and AMS-C ≥0.70. The AMS incidence (70% in NG vs. 60% in HG, p = 0.74), LL scores (7.1 ± 4.3 vs. 5.9 ± 3.4, p = 0.34), and AMS-C scores (1.50 ± 1.22 vs. 0.93 ± 0.81, p = 0.25) at the study endpoint were not significantly different between the groups. However, the incidence of AMS at 3611 m (6% vs. 47%, p = 0.01) and the functional LL score at 4559 m were lower in HG. Sp o 2 at 3611 m, heart rate during ascents, and arterial blood gases at 4559 m were not different between groups. We conclude that the tested program does not reduce the incidence of AMS within a rapid ascent to 4559 m, but our data show that it prevents AMS at lower altitudes. Whether such a program would prevent AMS at higher altitudes, but with slower ascent, remains to be tested.
Bjursten, Henrik, Per Ederoth, Engilbert Sigurdsson, Magnus Gottfredsson, Ingvar Syk, Orri Einarsson, and Tomas Gudbjartsson. S100B profiles and cognitive function at high altitude. High Alt. Med. Biol. 11:31–38, 2010.—Exposure to high altitude can lead to acute mountain sickness (AMS) and high altitude cerebral edema (HACE). In this study we investigated the effect of high altitude on neurocognitive function and S100B release. Increased S100B release has been hypothesized to signify a loss of integrity in the blood–brain barrier (BBB). Seven healthy volunteers trekked to Capanna Regina Margherita (4554 m above sea level) in the Monte Rosa massif. During ascent and descent, five test events were undertaken; participants underwent neurocognitive testing, Lake Louise scoring (LLS), and blood sampling to measure levels of S100B. The blood tests revealed that S100B levels increased 42% to 122% from baseline, and mean LLS increased from 0.57 to 2.57. A significant correlation was observed between both S100B levels and LLS and S100B and some neurocognitive scores. The study indicates that S100B can be released by a mild hypoxia during AMS. Moreover, an observed correlation between S100B and a lower score on neurocognitive tests suggests that the pathogenetic mechanisms may be linked. The study indicates that a decline in cognitive function is associated with symptoms of AMS.
Mariggiò, Maria A., Stefano Falone, Caterina Morabito, Simone Guarnieri, Alessandro Mirabilio, Raffaele Pilla, Tonino Bucciarelli, Vittore Verratti, and Fernanda Amicarelli. Peripheral blood lymphocytes: a model for monitoring physiological adaptation to high altitude. High Alt. Med. Biol. 10:333–342, 2010.—Depending on the absolute altitude and the duration of exposure, a high altitude environment induces various cellular effects that are strictly related to changes in oxidative balance. In this study, we used in vitro isolated peripheral blood lymphocytes as biosensors to test the effect of hypobaric hypoxia on seven climbers by measuring the functional activity of these cells. Our data revealed that a 21-day exposure to high altitude (5000 m) (1) increased intracellular Ca 2+ concentration, (2) caused a significant decrease in mitochondrial membrane potential, and (3) despite possible transient increases in intracellular levels of reactive oxygen species, did not significantly change the antioxidant and/or oxidative damage-related status in lymphocytes and serum, assessed by measuring Trolox-equivalent antioxidant capacity, glutathione peroxidase activity, vitamin levels, and oxidatively modified proteins and lipids. Overall, these results suggest that high altitude might cause an impairment in adaptive antioxidant responses. This, in turn, could increase the risk of oxidative-stress-induced cellular damage. In addition, this study corroborates the use of peripheral blood lymphocytes as an easily handled model for monitoring adaptive response to environmental challenge.
Brothers Michael D., Brandon K. Doan, Michael F. Zupan, Al L. Wile, Randall L. Wilber, and William C. Byrnes. Hematological and physiological adaptations following 46 weeks of moderate-altitude residence. High Alt. Med. Biol. 199-208, 2010-. Although acclimatization to moderate altitude (MA) is thought to be unnecessary or to require minimal adaptation, retrospective data from the U. S. Air Force Academy (USAFA), a military college located at 2210 m, suggested otherwise. To further examine the utility of USAFA as a model for MA acclimatization, a longitudinal experimental design was prospectively utilized to determine the magnitude and time course of selected hematological and performance parameters following 46 weeks at this unique MA setting. Incoming USAFA male freshmen (n = 55) were divided into experimental groups based on prior residence at sea level (SL) or MA. Hematological and performance parameters were repeatedly assessed during their entire first year at MA. Hematological data consisted of a complete blood count (CBC) with reticulocyte parameters, as well as determination of serum levels of ferritin, erythropoietin, and soluble transferrin receptor (sTfR). Performance testing included aerobic (1.5-mile run) and physical (push-ups, sit-ups, pull-ups, and standing long jump) fitness tests, maximal aerobic capacity, and running economy. Significant (p < 0.05; main effect) hematological differences between SL and MA subjects were observed for the majority of the study. MA subjects had a significantly higher hemoglobin concentration ([Hb], +5.5%), hematocrit (+2.8%), and serum ferritin (+59.0%) and significantly lower sTfR (-11.4%) values than their SL peers. Although both serum ferritin and sTfR demonstrated a significant altitude group x time interaction, [Hb] and hematocrit did not. A significant main effect of altitude without interaction was also observed for performance parameters, with SL subjects having a significantly lower Vo(2)peak (-5.9%), slower 1.5- mile run time (+5.4%), poorer running economy (+6.6%), and lower composite physical fitness test score (-13.9%) than MA subjects. These results suggest that complete acclimatization to 2210m by former SL residents may require lengthy physiological adaptations, as both hematological and physical performance differences persisted between groups. Further research at this uniquely well controlled MA setting is warranted.
The Caudwell Xtreme Everest (CXE) expedition involved the detailed study of 222 subjects ascending to 5300 m or higher during the first half of 2007. Following baseline measurements at sea level, 198 trekker-subjects trekked to Everest Base Camp (EBC) following an identical ascent profile. An additional group of 24 investigator-subjects followed a similar ascent to EBC and remained there for the duration of the expedition, with a subgroup of 14 collecting data higher on Everest. This article focuses on published data obtained by the investigator-subjects at extreme altitude (>5500 m). Unique measurements of peak oxygen consumption, middle cerebral artery diameter and blood velocity, and microcirculatory blood flow were made on the South Col (7950 m). Unique arterial blood gas values were obtained from 4 subjects at 8400 m during descent from the summit of Everest. Arterial blood gas and microcirculatory blood flow data are discussed in detail
Wang, Pei, Alice Y. N. Ha, Kenneth K. Kidd, Michael S. Koehle, and Jim L. Rupert. A variant of the endothelial nitric oxide synthase gene ( NOS3 ) associated with AMS susceptibility is less common in the Quechua, a high altitude native population. High Alt. Med. Biol. 20:27–30, 2010.— Endothelial nitric oxide synthase (eNOS) is a vascular enzyme that produces nitric oxide, a transient signaling molecule that by vasodilatation regulates blood flow and pressure. Nitric oxide is believed to play roles in both short-term acclimatization and long-term evolutionary adaptation to environmental hypoxia. Several laboratories, including ours, have shown that variants in NOS3 (the gene encoding eNOS) are overrepresented in individuals with altitude-related illnesses such as high altitude pulmonary edema (HAPE) and acute mountain sickness (AMS), suggesting that NOS3 genotypes contribute to altitude tolerance. To further test our hypothesis that the G allele at the G894T polymorphism in NOS3 (dbSNP number: rs1799983; protein polymorphism Glu298Asp) is beneficial in hypoxic environments, we compared frequencies of this allele in an altitude-adapted Amerindian population, Quechua of the Andean altiplano, with those in a lowland Amerindian population, Maya of the Yucatan Peninsula. While common in both populations, the G allele was significantly more frequent in the highlanders. Taken together, our data suggest that this variant in NOS3 , which has been previously associated with higher levels of nitric oxide, contributes to both acclimatization and adaptation to altitude.
Richalet, Jean-Paul. Operation Everest III: COMEX '97. High Alt. Med. Biology 11 121-132, 2010.-Eight male volunteers, aged 23 to 37, were selected to participate in a simulated ascent to 8848m in a hypobaric chamber. They were first preacclimatized in the Observatoire Vallot ( 4350 m) before entering the chamber. The chamber was progressively decompressed down to 253 mmHg barometric pressure, with a recovery period of 3 days at 5000m from days 20 to 22. They spent a total of 31 days in the chamber. Seventeen protocols were organized by 14 European teams to explore the limiting factors of physical and psychological performance and the physiological and pathological changes in various systems ( cardiac function, control of ventilation, autoregulation of cerebral blood flow, energy balance and body composition, muscle performance, erythropoiesis, and cognitive functions). All subjects reached 8000 m, and 7 of them reached the simulated altitude of 8848 m. Three subjects complained of transient neurological symptoms, which resolved rapidly with reoxygenation. At 8848m (n=5), Pao(2) was 30.6 +/- 1.4 mmHg, Pco(2) was 11.9 +/- 1.4 mmHg, and pH was 7.58 +/- 0.02 (arterialized capillary blood). Vo(2)max decreased by 59% at 7000m and increased by 9% at 6000m after plasma expansion, suggesting a role of altitude-induced plasma contraction in the reduction in Vo(2)max. Cardiac contractility was normal, but relaxation was slightly impaired. Autoregulation of cerebral blood flow was impaired at 8000 m. Negative energy balance was essentially caused by a decrease in appetite. Increased membrane lipid peroxidation could explain alterations in muscle or cognitive function. The subjects reached the "summit'' in better physiological conditions than would have been possible in the mountains, probably because acclimatization and other environmental factors such as cold and nutrition were controlled.