Aspects of physical activity in high altitude natives

Altitude adaptation was measured at sea level and high altitudes in sea level adapted and high altitude adapted natives. Tests of work capacity as measured by O₂ consumption, pulse rate, and ventilation rate are reported. It is noted that comparing our results with those of other investigators is difficult due to variations in terminology and procedure. This suggests the necessity of more precise definitions in studies of the physical activity of high altitude natives.     

Neutral and functionally important genes shed light on phylogeography and the history of high‐altitude colonization in a widespread New World duck

Phylogeographic studies often infer historical demographic processes underlying species distributions based on patterns of neutral genetic variation, but spatial variation in functionally important genes can provide additional insights about biogeographic history allowing for inferences about the potential role of adaptation in geographic range evolution. Integrating data from neutral markers and genes involved in oxygen (O₂)‐transport physiology, we test historical hypotheses about colonization and gene flow across low‐ and high‐altitude regions in the Ruddy Duck (Oxyura jamaicensis), a widely distributed species in the New World. Using multilocus analyses that for the first time include populations from the Colombian Andes, we also examined the hypothesis that Ruddy Duck populations from northern South America are of hybrid origin. We found that neutral and functional genes appear to have moved into the Colombian Andes from both North America and southern South America, and that high‐altitude Colombian populations do not exhibit evidence of adaptation to hypoxia in hemoglobin genes. Therefore, the biogeographic history of Ruddy Ducks is likely more complex than previously inferred. Our new data raise questions about the hypothesis that adaptation via natural selection to high‐altitude conditions through amino acid replacements in the hemoglobin protein allowed Ruddy Ducks to disperse south along the high Andes into southern South America. The existence of shared genetic variation with populations from both North America and southern South America as well as private alleles suggests that the Colombian population of Ruddy Ducks may be of old hybrid origin. This study illustrates the breadth of inferences one can make by combining data from nuclear and functionally important loci in phylogeography, and underscores the importance of complete range‐wide sampling to study species history in complex landscapes.     

Stepwise colonization of the Andes by Ruddy Ducks and the evolution of novel β‐globin variants

Andean uplift played a key role in Neotropical bird diversification, yet past dispersal and genetic adaptation to high‐altitude environments remain little understood. Here we use multilocus population genetics to study population history and historical demographic processes in the ruddy duck (Oxyura jamaicensis), a stiff‐tailed diving duck comprising three subspecies distributed from Canada to Tierra del Fuego and inhabiting wetlands from sea level to 4500 m in the Andes. We sequenced the mitochondrial DNA, four autosomal introns and three haemoglobin genes (α^A, α^D, β^A) and used isolation‐with‐migration (IM) models to study gene flow between North America and South America, and between the tropical and southern Andes. Our analyses indicated that ruddy ducks dispersed first from North America to the tropical Andes, then from the tropical Andes to the southern Andes. While no nonsynonymous substitutions were found in either α globin gene, three amino acid substitutions were observed in the β^A globin. Based on phylogenetic reconstruction and power analysis, the first β^A substitution, found in all Andean individuals, was acquired when ruddy ducks dispersed from low altitude in North America to high altitude in the tropical Andes, whereas the two additional substitutions occurred more recently, when ruddy ducks dispersed from high altitude in the tropical Andes to low altitude in the southern Andes. This stepwise colonization pattern accompanied by polarized β^A globin amino acid replacements suggest that ruddy ducks first acclimatized or adapted to the Andean highlands and then again to the lowlands. In addition, ruddy ducks colonized the Andean highlands via a less common route as compared to other waterbird species that colonized the Andes northwards from the southern cone of South America.     

Internal carotid and vertebral arterial flow velocity in men at high altitude

Cerebral blood flow increases at high altitude, but the mechanism of the increase and its role in adaptation to high altitude are unclear. We hypothesized that the hypoxemia at high altitude would increase cerebral blood flow, which would in turn defend O2 delivery to the brain. Noninvasive Doppler ultrasound was used to measure the flow velocities in the internal carotid and the vertebral arteries in six healthy male subjects. Within 2-4 h of arrival on Pikes Peak (4,300 m), velocities in both arteries were slightly and not significantly increased above sea-level values. By 18-44 h a peak increase of 20% was observed (combined P less than 0.025). Subsequently (days 4-12) velocities declined to values similar to those at sea level. At altitude the lowest arterial O2 saturation (SaO2) and the highest end-tidal PCO2 was observed on arrival. By day 4 and thereafter, when the flow velocities had returned toward sea-level values, hemoglobin concentration and SaO2 were increased over initial high-altitude values such that calculated O2 transport values were even higher than those at sea level. Although the cause of the failure for cerebral flow velocity to increase on arrival is not understood, the subsequent increase may act to defend brain O2 transport. With further increase in hemoglobin and SaO2 over time at high altitude, flow velocity returned to sea-level values.     

A comparative study on the effect of training at altitude and at sea level on endurance and certain biochemical variables

The aim of this study was to ascertain the effects of training at altitude (1750 m. PB = 630mmHg) and at sea level (10m, PB = 760mmHg) as well as that of a period of adaptation of originally sea level-trained rats at altitude on endurance capacity. The average run time to exhaustion was 185.3 +/- 3.7 min for rats trained at altitude in comparison with 150.0 +/- 10.3 min for sea level-trained rats. After 14 days of adaptation at altitude, no significant difference in running time to exhaustion between rats trained at altitude (189.0 +/- 16.4 min) and those trained at sea level (177.2 +/- 11.6 min) was apparent. The improved endurance capacity of rats trained at altitude (when tested at altitude) is probably attributable to an increased respiratory capacity as is evident from the significantly increased levels of the citric acid cycle marker enzyme, citrate synthase (citrate oxaloacetate-lyase, EC 4.1.3.7) in the liver and gastrocnemius muscle of rats trained at altitude as compared to those trained at sea level.     

Predicted structural change in erythropoietin of plateau zokors--adaptation to high altitude

Erythropoietin (EPO) is a glycoprotein hormone, expressed mainly in fetus liver and adult kidneys. EPO plays an important role in enhancing red blood cell formation in bone marrow under hypoxia. Plateau zokor (Myospalax baileyi), an subterranean burrowing endemic rodent inhabiting areas of 2 800-4 200 m above sea level on Qinghai-Tibet Plateau, is a typical high hypoxia tolerant mammal with high ratio of oxygen utilization in adaptation to the harsh plateau environment. To investigate the possible mechanisms of adaptation of plateau zokor EPO to high altitude, the complete cDNA and amino acid sequences of plateau zokor EPO have been described. Phylogenetic tree of Epo showed the convergence of the Spalax and Myospalax, indicating that, the convergent evolution was driven by similar hypoxic ecological niches. Our results showed that some common sites under positive selection in zokor (116M and 144A) and Spalax (102R, 116M, 144A and 152P) are the important sites for Epo biological activity. This study thus reports a gene level observation which may be involved in adaptation to underground life at high altitude.     

Thoracic adaptation to high altitude

Growth in the thoracic region and its adaptation to higher altitude was investigated in boys between 5 to 18 years of Rajput origin at two altitudes, i. e. Rampur Bushahr (800 m above sea level) and Kinnaur (3,000 m above sea level). Both places are located in Himachal Pradesh. The sample includes 405 individuals From Bushahr and 676 individuals from Kinnaur. The results of this study reveal that as the higher altitudes are attained the vital capacity also increases relatively more, and these differences become more pronounced after adolescence, indicating longer time of apnoea. The population living at higher altitudes is also characterised by a significant greater chest length.     

Hemoglobin levels in a Himalayan high altitude population

This report presents data on hemoglobin concentrations in a sample of Himalayan high altitude natives measured at their habitual altitude of residence. In this sample of 270 healthy Tibetan adults resident at 3250–3560 m in Upper Chumik, Nepal, the mean hemoglobin concentration is 16.1 ± 1.2 gm/dl among adult males, 14.4 ± 1.4 gm/dl among premenopausal and 15.0 ± 1.1 gm/dl among postmenopausal adult females. 123 of 126 (98%) males, 96 of 100 (96%) premenopausal and 36 of 44 (82%) postmenopausal females have hemoglobin concentrations within two standard deviations of the sea level mean. These data demonstrate that a healthy population may reside at high altitude without the degree of elevation in hemoglobin widely known and cited for Andean highlanders. Comparing published data on mean hemoglobin concentrations of adult Himalayan and Andean samples residing between 3200 m and 4100 m reveals that Himalayan means are systematically lower. This in turn may account for the reported population differences in the prevalence of chronic mountain sickness (Monge's disease). It is hypothesized that Himalayan and Andean highlanders represent alternative patterns of high altitude hematological adaptation.     

Effect of beta-adrenergic blockade on plasma lactate concentration during exercise at high altitude

When unacclimatized lowlanders exercise at high altitude, blood lactate concentration rises higher than at sea level, but lactate accumulation is attenuated after acclimatization. These responses could result from the effects of acute and chronic hypoxia on beta-adrenergic stimulation. In this investigation, the effects of beta-adrenergic blockade on blood lactate and other metabolites were studied in lowland residents during 30 min of steady-state exercise at sea level and on days 3, 8, and 20 of residence at 4300 m. Starting 3 days before ascent and through day 15 at high altitude, six men received propranolol (80 mg three times daily) and six received placebo. Plasma lactate accumulation was reduced in propranolol- but not placebo-treated subjects during exercise on day 3 at high altitude compared to sea-level exercise of the same percentage maximal oxygen uptake (VO2max). Plasma lactate accumulation exercise on day 20 at high altitude was reduced in both placebo- and propranolol-treated subjects compared to exercise of the same percentage VO2max performed at sea level. The blunted lactate accumulation during exercise on day 20 at high altitude was associated with reduced muscle glycogen utilization. Thus, increased plasma lactate accumulation in unacclimatized lowlanders exercising at high altitude appears to be due to increased beta-adrenergic stimulation. However, acclimatization-induced changes in muscle glycogen utilization and plasma lactate accumulation are not adaptations to chronically increased beta-adrenergic activity.     

Body structure and respiratory efficiency among high altitude Himalayan populations

To understand the morphological and physiological variations among the temporary and permanent residents of high altitude, this study was undertaken at Leh, Ladakh. It is situated at 3500 m (11500 feet) above sea level, the mean barometric pressure was 500 tors and air temperature varied from 2 degrees C to 20 degrees C. The highland Tibetans showed broadest chest and most developed musculature closely followed by Ladakhi Bods. These high altude natives also displayed significantly higher value of vital capacity, forced vital capacity, and inspiratory capacity. The better respiratory efficiency observed among high altitude residents indicates higher degree of adaptation to high altitude hypoxia. Temporary residents were observed to be tallest and fattest with lower trunk fat predominance of all the four groups and showed narrowest chest and lower respiratory efficiency as compared to high altitude natives. The duration of stay at high altitude has clearly brought about a perceptible difference in body dimensions and respiratory functions of various groups of adult males studied at same altitude.     

Systemic and organ mechanisms of the organism oxygen supply in high altitude

Organ and systemic mechanisms of organism oxygen supply in adaptation to high altitude of the Tien Shan (3200 m above sea level) were studied in the experiments on dogs. It is shown that in the first few days in the mountains (5-7th and 15th days) oxygen supply of the body is due to the increased delivery of O2 to organs and tissues; in the process of adaptation (30 days), the efficiency of tissue utilization of O2 increases. Changes of organ blood flow in visceral and somatic organs, features of compensation of the tissue hypoxia and oxygen supply of the heart, brain, skeletal muscle in different periods of adaptation to high altitude were established.     

Changes in plasma lipids and lipoprotein cholesterol during a high altitude mountaineering expedition (4800 m)

Effects of high altitude exposure on plasma lipids and lipoprotein cholesterol were studied in 8 mountaineers who spent 3 weeks at the Annapurna IV base camp (4800 m) after a 12 day trek. In spite of the moderate physical exertion at the camp, the loss of body weight was more pronounced during the stay at high altitude than during the trekking period. Compared with baseline values observed at sea level, marked reductions in plasma cholesterol (-27%) and phospholipids (-19%) were found 3 days after arrival at the camp and persisted during the next 17 days. A less marked fall in plasma triglycerides occurred, weakly significant at the end of the stay. Because there were no relevant changes in very low density lipoproteins or in high density lipoprotein (HDL)-cholesterol, the low plasma cholesterol levels at the high altitude resulted mainly from the reduction in low density lipoprotein (LDL)-cholesterol: the mean HDL/LDL cholesterol ratio changed from 0.39 at sea level to 0.63 at the end of the stay at 4800 m. Fluctuations in LDL-cholesterol were not concomitant with those in body weight and were independent of the exercise training during the expedition. This study shows moreover that the early drop in LDL-cholesterol was associated with an opposite change in plasma levels of catecholamines and thyroid hormones. Taking into account that such hormonal responses are classically observed at high altitude, the concomitant decrease in LDL-cholesterol might be interpreted as being a relevant adaptative response to hypoxic conditions at high altitude.     

Molecular cloning and characterization of hemoglobin alpha and beta chains from plateau pika (Ochotona curzoniae) living at high altitude

Hemoglobin (Hb) plays an important role in oxygen transfer from lung to tissues. Possession of a Hb with high oxygen affinity helps highland animals to adapt to high altitude, has been studied profoundly. Plateau pika (Ochotona curzoniae), a native species living at 3,000-5,000 m above sea level on Qinghai-Tibet Plateau, is a typical hypoxia and low temperature tolerant mammal. To investigate the possible mechanisms of plateau pika Hb in adaptation to high altitude, the complete cDNA and amino acid sequences of plateau pika hemoglobin alpha and beta chains have been described. Compared with human Hb, alterations in important regions can be noted: alpha111 Ala-->Asn, beta35 Tyr-->Phe, beta112 Cys-->Val, beta115 Ala-->Ser, and beta125 Pro-->Gln. Phylogenetic analysis of alpha and beta chains shows that plateau pika is closer to rabbit than to other species. This study provides essential information for elucidating the possible roles of hemoglobin in adaptation to extremely high altitude in plateau pika.     

Modulation of urinary peptidome in humans exposed to high altitude hypoxia

The exposure of healthy subjects to high altitude represents a model to explore the pathophysiology of diseases related to tissue hypoxia and to evaluate pharmacological approaches potentially useful as a therapy for chronic diseases related to hypoxia. We explored the urinary peptidome to detect alterations induced by the exposure of subjects to different altitudes (sea level, high altitude = 3500 m, very high altitude = 5400 m) and to pharmacological treatment. Urine samples were collected from 47 subjects, randomly and blindly assigned to placebo (n = 24) or Telmisartan (n = 23). Samples were purified by the use of magnetic beads, then analysed by MALDI-TOF MS. Results showed that the urinary peptidome is not affected by the administration of Telmisartan, neither at the sea level nor at high and very high altitudes. In contrast, the urinary protein profiles are modified when subjects are exposed to high and very high altitudes, and we detected six peptides differentially expressed in hypobaric hypoxia at high or very high altitude compared to the sea level. Two of them were identified as fragments of the glycoprotein uromodulin and of the α1-antitrypsin. This is the first proteomic study showing that hypobaric hypoxia conditions affect the urinary peptidome.     

Skeletal muscle changes after endurance training at high altitude.

The effects of endurance training on the skeletal muscle of rats have been studied at sea level and simulated high altitude (4,000 m). Male Wistar rats were randomly assigned to one of four groups: exercise at sea level, exercise at simulated high altitude, sedentary at sea level, and sedentary at high altitude (n = 8 in each group). Training consisted of swimming for 1 h/day in water at 36 degrees C for 14 wk. Training and exposure to a high-altitude environment produced a decrease in body weight (P less than 0.001). There was a significant linear correlation between muscle mass and body weight in the animals of all groups (r = 0.89, P less than 0.001). High-altitude training enhanced the percentage of type IIa fibers in the extensor digitorum longus muscle (EDL, P less than 0.05) and deep portions of the plantaris muscle (dPLA, P less than 0.01). High-altitude training also increased the percentage of type IIab fibers in fast-twitch muscles. These muscles showed marked metabolic adaptations: training increased the activity levels of enzymes involved in the citric acid cycle (citrate synthase, CS) and the beta-oxidation of fatty acids (3 hydroxyacyl CoA dehydrogenase, HAD). This increase occurred mainly at high altitude (36 and 31% for HAD in EDL and PLA muscles; 24 and 31% for CS in EDL and PLA muscles). Training increased the activity of enzymes involved in glucose phosphorylation (hexokinase). High-altitude training decreased lactate dehydrogenase activity. Endurance training performed at high altitude and sea level increased the isozyme 1-to-total lactate dehydrogenase activity ratio to the same extent.(ABSTRACT TRUNCATED AT 250 WORDS)     

拉萨高原居民肺容量的测定

对年龄、身高和体重相同的拉萨男性世居藏族39人和男性移居汉族43人的肺容量进行了测定。结果显示:藏族组的肺活量(VC)、肺总容量、胸围均大于汉族组,残气量有大于汉族组之趋势(P=0.06)。胸围的大小与VC呈正相关。5岁前和18岁后移居高原者之肺容量无差别。结果提示,拉萨世居藏族具有较大的肺容量,这对提高肺弥散功能和维持运动时的血氧饱和度有重要意义。     

Effects of high altitude stay on the incidence of common diseases in man

Prolonged stay at high altitude significantly lowers the incidence of some of the diseases commonly encountered at sea level. This conclusion is based on a study involving 130,700 men stationed on plains between 760 m and sea level and 20,000 men stationed at altitudes between 3692 and 5538 m during the period 1965 to 1972. When yearwise differences in morbidity rates were determined for this period it was found that apart from amoebic hepatitis, goitre and lobar pneumonia, which show a higher incidence, the incidence of infections of bacterial, viral and protozoal origin, diabetes mellitus, hypertension and ischaemic heart disease, asthma and rheumatoid arthritis, gastric disorders, skin diseases, psychiatric ailments and anaemia was significantly lower at high altitude than at sea level. When the trend in morbidity rates was compared over the two subperiods of 1965 to 1968 and 1969 to 1972 it was found that generally increasing or decreasing trends on plains were reflected at high altitude. The overall incidence at high altitude however remained low. Part I of our communication deals with epidemiological data and these findings. Part II surveys the available literature and attempts to explain how improved hormonal state, enhanced fibrinolytic activity, accelerated humoral and cellular immune responses, favourable haemodynamics, better cardiac and cerebral functions, improved metabolic functions, and a relatively stable, dry and cold climate favourably influence the incidence of diseases at high altitude.     

Effect of high altitude on sensitivity to the taste of phenylthiocarbamide

Sensitivity to the taste of phenylthiocarbamide (PTC) was studied using the Harris-Kalmus method in healthy human volunteers at sea level and then subsequently at an altitude of 3500 m over a period of 3 weeks, after which they were brought back to sea level. Blood sugar, insulin and blood cortisol levels were estimated weekly. The results indicated that, out of 51 subjects studied, 26 (55%) were PTC tasters at sea level. Eight of those unable to taste PTC at sea level tested as tasters at high altitude, and 2 of them reverted to being non-tasters on return to sea level. In the blood, an increase in cortisol and blood insulin levels was seen without any significant change in sugar levels. All the changes recorded at high altitude tended to return to basal values after re-induction to sea level. The study suggests that high-altitude hypoxia in some way, possibly involving changes in hormonal profile among other factors, causes an alteration in sensitivity to the taste of PTC, resulting in some of the individuals shifting to lower PTC sensitivity. Received: 24 November 1999 / Accepted: 25 January 2000     

Body water metabolism in high altitude natives during and after a stay at sea level

Body fluid compartments were studied in a group of high altitude natives after a stay of two months at sea level and during 12 days at an altitude of 3,500 m. Measurements of total body water and extracellular water were made on day 3 and 12 of reinduction to altitude, while plasma volume was measured on day 12 only. The intracellular water, blood volume and red cell mass were computed from the above parameters. Total body water and intracellular water decreased by 3.3% (P<0.001) and 5.0% (P<0.001) respectively by the 3rd day at altitude and did not change thereafter. Extracellular water increased progressively at altitude, but the increase was not significant. Blood volume and red cell mass increased significantly while plasma volume decreased at altitude. These data were compared with that of low landers. This study suggested body hypohydration on high altitude induction in low landers as well as in high altitude natives on reinduction.     

Alkaline shift in lumbar and intracranial CSF in man after 5 days at high altitude.

In six healthy male volunteers at sea level (PB 747-759 Torr), we measured pH and PCO2 in cerebrospinal fluid (CSF), and in arterial and jugular bulb blood; from these data we estimated PCO2 (12) and pH for the intracranial portion of CSF. The measurements were repeated after 5 days in a hypobaric chamber (PB 447 Torr). Both lumbar and intracranial CSF were significantly more alkaline at simulated altitude than at sea level. Decrease in [HCO3-] IN lumbar CSF at altitude was similar to that in blood plasma. Both at sea level and at high altitude, PCO2 measured in the lumbar CSF was higher than that estimated for the intracranial CSF. At altitude, hyperoxia, in comparison with breathing room air, resulted in an increase in intracranial PCO2, and a decrease in the estimated pH in intracranial CSF. With hyperoxia at altitude, alveolar ventilation was significantly higher than during sea-level hyperoxia or normoxia, confirming that a degree of acclimatization had occurred. Changes in cerebral arteriovenous differences in CO2, measured in three subjects, suggest that cerebral blood flow may have been elevated after 5 days at altitude.