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PubMed1998

[High altitude pulmonary edema. Study of 21 cases].

BACKGROUND: The effect of altitude on subjects between 8 to 22 and 23 to 51 years, that resided at sea level, or in the highlands, and developed altitude lung edema, is presented in series of 21 prospective registered patients at 4,800 to 5,000 m altitude in the Andes mountains of Ecuador. PATIENTS MATERIAL AND METHODS: The 21 sick patients were evaluated at 2 h and at 8 hr after exposition to the high altitude. They were immediately evacuated from the high altitudes. Clinical and radiological methods were used. The statistical analysis was performed with chi(2) test with Yates correction and relative risk. RESULTS: The younger patients tended to develop illness with a higher frequency (p < 0.01). The place of residence influenced the development of the illness only for the group of persons between the ages of 23 to 51 years (p < 0.03); and also in comparing all of the subjects from the coast with those from the highlands. CONCLUSIONS: A inverse relationship was found between the age and the possibility of the development of altitude pulmonary edema, possibly due t a basic incrementation of the pressure of the pulmonary artery, or because of a relative immaturity of the adaptative mechanisms. The place of residence was significantly associated with a higher frequency of pulmonary edema in persons between the ages of 23 to 51 years.

Adolescent↗
PubMed1998

A loglogistic model for altitude decompression sickness.

BACKGROUND: Altitude decompression sickness (DCS) is a potential hazard encountered during high altitude flights or during extravehicular activity in space. In this study, the loglogistic distribution was used to model DCS risk and symptom onset time. METHODS: The Air Force Research Laboratory, Brooks AFB, TX, has conducted studies on human subjects exposed to simulated altitudes in hypobaric chambers. The dataset from those studies was used to develop the DCS models and consisted of 975 subject-exposures to various altitudes, preoxygenation times, and exercise regimens. Since the risk of DCS is known to increase over time at altitude, and then decrease because of denitrogenation, the loglogistic model was fit to the data. The model assumes that the probability of DCS depends on several risk factors. Maximum likelihood estimates of the parameters were obtained using the statistical software package SAS. Cross validation techniques were provided to examine the goodness of fit of the model. RESULTS: The fitted model indicated that altitude, ratio of preoxygenation to exposure time, and exercise were the most significant risk factors. The model was used to predict the risk of DCS for a variety of exposure profiles. The predicted probability of DCS agreed very closely with the actual percentages in the database. CONCLUSION: The loglogistic distribution was found to be appropriate for modeling the risk of DCS. Based on the cross validation and validation results, we conclude that this model provides good estimates of the probability of DCS over time.

Adolescent↗
PubMed1976

Responses of the autonomic nervous system during acclimatization tp high altitude in man.

A study has been conducted on 20 sojourners, between the ages of 20-30 years, to evaluate responses of the autonomic nervous system during acclimatization to high altitude. The responses measured consisted of heart rate (HR), blood pressure (BP), oral temperature (Tor), mean skin temperature (Tsk), cold pressor response (CPR), orthostatic tolerance to tilt, and urinary catecholamines. The subjects were tested initially at Delhi (altitude 260 m) and thereafter, on acute induction to an altitude of 3500 m periodically for 3 weeks. For comparison, the same responses were studied on 10 acclimatized lowlanders (AL) who had been staying at the same altitude for more than a year and on 10 high-altitude natives (HAN). The studies showed a rise in HR, BP, Tor, and urinary catecholamines, and a fall in Tsk, CPR, and orthostatic tolerance immediately on arrival at HA, indicating a relative hyperactivity of the sympathetic system. After a stay of 1 week, there was a gradual recovery in all the responses, though sympathetic hyperactivity was still maintained throughout the 3 weeks of stay. In AL also there was a preponderance of sympathetic activity, though of relatively lesser magnitude than that seen in sojourners. In HAN, on the other hand, there was a relative parasympathetic predomination. It has been concluded that in lowlanders it takes more than a year of stay at altitude for complete recovery of autonomic balance.

Acclimatization↗
PubMed1999

Heart rate variability in 1-day-old infants born at 4330 m altitude.

In fetuses and newborn infants heart rate variability changes in conditions of acute and chronic hypoxia; we therefore asked whether heart rate variability of infants born at high altitude differed from that of low-altitude infants. Short-term recordings (4-5 min) of inter-beat intervals were obtained in 19 infants in Lima (50 m altitude) and in 15 infants in Cerro de Pasco (4330 m, barometric pressure approximately 450 mmHg, inspired oxygen pressure approximately 94 mmHg) during quiet rest in warm conditions (ambient temperature, Ta, approximately 35 degrees C). In 12 infants from each group recordings were also obtained during cooling (Ta approximately 26 degrees C). Heart rate variability was evaluated from 512 consecutive inter-beat intervals, with analysis based on time-domain and frequency-domain methods. At warm Ta, heart rate variability did not differ between the two groups. During cooling, heart rate increased only in the low-altitude group. As in the warm, during cooling most parameters of heart rate variability did not differ between the two groups. The only exception was the inter-beat interval power of the high-frequency range of the spectrum (0.15-0.4 Hz), which, at least in adults, is believed to be a reflection of vagal activity, and was greater in the high-altitude group. It is concluded that gestation at high altitude, despite its blunting effects on fetal growth, does not have a major impact on heart rate variability of the newborn. Nevertheless, the possibility that differences in response to cooling may reflect some limitation in heart rate control needs to be examined further.

Altitude↗
PubMed2000

Morphological growth of Han boys and girls born and raised near sea level and at high altitude in western China.

This study compares the morphological characteristics of Han children, adolescents, and young adults who were born at 250 m near Beijing and at three high altitudes in Qinghai Province, Peoples Republic of China (3,200 m, 3,800 m, and 4,300 m). From ages 6 through 15, Han children growing up at high altitudes are significantly shorter, lighter, have less fat, and are less muscular than Han children growing up at low altitude. However, older adolescents and young adults show no such altitude differences. Younger adolescents and children in this study were all born after the government economic reforms of 1978. These reforms had a greater impact on the growth of children in and around large cities than on those in more remote areas. Therefore, the altitude differences in size among Han children ages 15 and younger may be a consequence of regional variation in health and nutrition, rather than due to the influence of hypoxia. There are no altitude-related differences in thorax dimensions among Han children, adolescents, or young adults. This suggests that hypoxia does not affect the thorax growth of Han children. Am. J. Hum. Biol. 12:665-681, 2000. Copyright 2000 Wiley-Liss, Inc.

Journal Article↗
PubMed2006

Mole-rats from higher altitudes have greater thermoregulatory capabilities.

Subterranean mammals (those that live and forage underground) inhabit a challenging microenvironment, with high levels of carbon dioxide and low levels of oxygen. Consequently, they have evolved specialised morphological and physiological adaptations. For small mammals that inhabit high altitudes, the effects of cold are compounded by low oxygen partial pressures. Hence, subterranean mammals living at high altitudes are faced with a uniquely demanding physiological environment, which presumably necessitates additional physiological adjustments. We examined the thermoregulatory capabilities of two populations of Lesotho mole-rat Cryptomys hottentotus mahali that inhabit a 'low' (1600 m) and a 'high' (3200 m) altitude. Mole-rats from the high altitude had a lower temperature of the lower critical point, a broader thermoneutral zone, a lower thermal conductance and greater regulatory non-shivering thermogenesis than animals from the lower altitude. However, minimum resting metabolic rate values were not significantly different between the populations and were low compared with allometric predictions. We suggest that thermoregulatory costs may in part be met by animals maintaining a low resting metabolic rate. High-altitude animals may adjust to their cooler, more oxygen-deficient environment by having an increased non-shivering thermogenesis whilst maintaining low thermal conductance.

Acclimatization↗
PubMed2005

Everest nails: a prospective study on the incidence of Beau's lines after time spent at high altitude.

Beau's lines are transverse grooves seen in the nails that appear after a period of disruption in nail matrix formation. The fall in atmospheric pressure at high altitude causes hypobaric hypoxia in individuals spending time at high altitude, which may result in disruption of nail matrix formation and the appearance of Beau's lines. Members of an expedition to a research base camp at 5000 m in the Nepal Himalayas were contacted 4 and 8 weeks after returning to low altitude to report on the appearance of new transverse grooves in their nails. During the expedition, data on altitude, acute mountain sickness score, oxygen saturation, and the use of medications were collected by each individual in a twice-daily log book. Fifty-nine individuals consented to enroll in the study, with 52 (88%) contacted at follow-up at 8 weeks. The incidence of Beau's lines was 33%. There was no relationship to maximum altitude reached, minimum oxygen saturation, duration of various levels of hypoxia, worst AMS score, or length of stay above 4000 m (p = 0.118). The hypoxia associated with the hypobaric environment at high altitude could be sufficient to cause a disruption in nail matrix formation.

Adult↗
PubMed2006

Genome-wide analysis of high-altitude maize and gene knockdown stocks implicates chromatin remodeling proteins in response to UV-B.

A comparative analysis, by expression profiling of maize, was performed to identify novel components in the mechanisms of maize responses to UV-B. Five high-altitude landraces grown from 2,000 to 3,400 m naturally receive higher UV-B fluence than plants at lower altitudes and similar latitudes. These high-altitude landraces were compared directly with a low-altitude line and with literature reports for other temperate maize lines. A microarray analysis demonstrated that among the UV-B responsive transcripts, several types of gene implicated in chromatin remodeling are differentially expressed before and after UV-B treatment in high-altitude lines. RNAi transgenic plants with lower expression of four such chromatin-associated genes exhibited hypersensitivity to UV-B by measurements of leaf arching, increased leaf chlorosis and necrosis, and altered UV-B regulation of selected genes. These results collectively suggest that genes involved in chromatin remodeling are crucial for UV-B acclimation and that some high-altitude lines exhibit adaptations to this challenge.

Adaptation, Physiological↗
PubMed2007

Effects of altitude on circadian rhythm of adult locomotor activity in Himalayan strains of Drosophila helvetica.

BACKGROUND: We recently reported that the altitude of origin altered the photic and thermal sensitivity of the circadian pacemaker controlling eclosion and oviposition rhythms of high altitude Himalayan strains of Drosophila ananassae. The present study was aimed at investigating the effects of altitude of origin on the pacemaker controlling the adult locomotor activity rhythm of D. helvetica. METHODS: Locomotor activity rhythms of the high altitude Himalayan (haH) strain (Hemkund-Sahib, 4,121 m above sea level) and the low altitude Himalayan (laH) strain (Birahi, 1,132 m a.s.l.) of D. helvetica were assayed by two experiments. The first experiment examined the natural entrainment pattern in light-dark (LD) cycles at the breeding site of each strain. The second experiment examined the entrainment parameters in LD 12:12 cycles and the period of free-running rhythm in constant darkness (DD) under controlled laboratory conditions. RESULTS: When entrained by natural or artificial LD cycles, the haH strain had an unimodal activity pattern with a single peak that commenced in the forenoon and continued till evening, while the laH strain had a bimodal activity pattern in which the morning peak occurred before lights-on and was separated by about 4 h from the evening peak. Unimodality of the haH strain was retained in DD; however, bimodality of the laH strain was abolished in DD since the evening peak disappeared immediately after the trasfer from LD 12:12 to DD. The period of the free-running rhythm of the haH strain was ~26.1 h, whereas that of the laH strain was ~21.7 h. CONCLUSION: Parameters of entrainment and free-running rhythm of the adult locomotor activity of the haH strain of D. helvetica were strikingly different from those of the laH strain and were likely due to ecological adaptations to the prevailing environmental conditions at the altitude where the species evolved.

Journal Article↗
PubMed2000

Effects of moderate altitude on exhaled nitric oxide, erythrocytes lipid peroxidation and superoxide dismutase levels.

The purpose of this study was to investigate the effects of staying at a moderate altitude (2,300 m, 7 d) on the levels of plasma nitrite, exhaled nitric oxide (NO), malondialdehyde (MDA) and superoxide dismutase (SOD). Measurements were obtained from 9 female (mean age 18.3 +/- 2) and 9 male (mean age 19.3 +/- 3.7) cross-country volunteer skiers: before, during (1st day, 7th day) and after staying at a moderate altitude. Exhaled nitric oxide levels were measured only before and after staying at the altitude. Nitrite levels increased throughout the stay at the altitude, while MDA levels decreased. In parallel with the nitrite levels, SOD activities were also found to have increased. Exhaled NO values were decreased after the stay at the moderate altitude. These results show that altitude hypoxia causes decreased in NO levels in the lung but increased systemic NO levels in the blood due to inhibition of erythrocyte lipid peroxidation.

Administration, Inhalation↗
PubMed1991

Significance of delayed symptom onset and bubble growth in altitude decompression sickness.

Three characteristics of altitude induced decompression sickness (DCS) are: 1) symptoms occur some time after arrival at altitude; 2) symptoms seldom occur below 18,000 ft, even though bubbles are frequently detected at that low altitude; 3) symptoms seldom occur after 4 h at altitude. These observations could be explained if it were postulated that bubbles must reach a threshold size before symptoms of DCS occur. In vitro techniques were used in this study to measure bubble growth at various altitudes. The results indicate that although the growth rate of bubbles depends strongly on the altitude where they form, bubble growth requires time. This helps explain the first observation above. We found that bubbles stop growing early at a small size below 18,000 ft. This helps explain the second observation above. Finally, we found that bubbles stop growing when the fluid immediately surrounding the bubble is cleared of supersaturated gas regardless of the fluid composition a few centimeters from the bubble. This helps explain the last observation above.

Decompression Sickness↗
PubMed1984

Bilirubin metabolism in the rat at high altitude.

Bilirubin metabolism was studied in rats injected with unconjugated bilirubin (0, 0.5, 1.5, 3.0, or 4.5 mg X 100 g-1) after 2 and 6 weeks continuous exposure to 4,600 m (15,000 ft) simulated altitude. Exogenous loads of bilirubin were used to exceed any effect of polycythemia, thereby allowing assessment of defects in conjugation and excretion due to the exposure to high altitude. Rats given no exogenous bilirubin showed polycythemia when exposed to high altitude which may have contributed to the small but significant elevations in their serum bilirubin levels. Compared to sea-level controls, mean serum concentrations of total and unconjugated bilirubin were significantly elevated in altitude-exposed rats given exogenous bilirubin. Mean serum conjugated bilirubin levels did not rise at any dose. Thus, bilirubin uptake and/or conjugation rather than excretion are impaired in rats at high altitude. We conclude that while polycythemia may contribute to high altitude-induced bilirubinemia, an impairment in uptake and/or conjugation also exists.

Animals↗
PubMed2001

Weight loss at high altitude.

Loss of appetite and weight are frequently observed at altitudes above 5000 m. However, the pathophysiology behind changes in body composition at extreme altitude is still not fully understood. Proper acclimatization to altitude and high caloric intake minimizes, but can not completely prevent significant weight loss under the influence of hypobaric hypoxia. The discovery of leptin in 1994 has initiated a new research area investigating molecular networks that connect peripheral organs with the central nervous system to sense and regulate energy intake as well as energy expenditure. Since then, a whole microcosm of new hormones, neurotransmitters and receptors has been discovered and studied with respect to body weight control. Those agents include neuropeptide Y (NPY), agouti-related protein (AGRP), melanocortin receptors (MC-R), cocaine-amphetamine regulated transcript (CART), pro-opiomelanocortin (POMC), orexin A and B (hypocretins), melanin-concentrating hormone (MCH) and ghrelin (endogenous ligand of the growth hormone secretagogue receptor). This overview will introduce the current concepts of the molecular control of energy homeostasis and attempt to reexamine the effects of altitude on appetite and body composition in light of these concepts. An overview of studies on changes of appetite and body composition at high altitude will be followed by the presentation of recent data on changes of endocrine parameters at hypobaric hypoxia that could be involved in the pathophysiology of weight loss.

Altitude↗
PubMed2002

Postural ataxia at high altitude is not related to mild to moderate acute mountain sickness.

To evaluate the role of acute mountain sickness (AMS) in the pathogenesis of stance abnormalities occurring at high altitude, static posturography was applied to 22 healthy subjects at an altitude of 450 m and during a 3-day sojourn at 4559 m. Subjects stood on a platform and sway velocity (S), and sway velocity in the antero-posterior (S(AP)) and medio-lateral (S(ML)) directions was recorded for 20 s with eyes open (EO) and 20 s with eyes closed (EC). Arterialized blood from an ear lobe was analyzed to determine the arterial partial pressures of oxygen (PaO2) and carbon dioxide, and oxygen saturation (SaO2). AMS was assessed by the environmental symptom questionnaire (ESQ) of Sampson (cerebral AMS, AMS-C score > 0.7). AMS affected four subjects on day 1, ten subjects on day 2, and five subjects on day 3. Posturographic findings showed no difference between subjects with AMS and healthy subjects, and no correlation with the ESQ score. PaO2 and SaO2 showed non-significant trends toward lower values in subjects with AMS than in those without AMS. Posturographic parameters significantly worsened on the 1st (EO-S, P < 0.001; EC-S, P < 0.01; EO-SML, P < 0.05), 2nd (EO-S, EC-S and EO-SML, P < 0.01) and 3rd days (EC-S, P < 0.05) at high compared to low altitude. Differences in AMS-C score, SaO2 and PaO2 were significant between low and high altitude (P < 0.0001). Our data suggest that AMS is not important in the pathogenesis of postural ataxia occurring at high altitude.

Adult↗
PubMed1990

Acute mountain sickness at intermediate altitude: military mountainous training.

A US Marine Corps Battalion Landing Team (BLT) of 638 men was deployed on a winter training exercise to an altitude of 2,065 to 2,620 m. Nine marines (1.4%) presented to the medical officers with incapacitating symptoms consistent with acute mountains sickness. Seven were treated with acetazolamide and experienced relief of their symptoms within 24 hours. The incidence of nonspecific complaints associated with acute mountain sickness at altitude was found to be significantly greater than the incidence at sea level of those same complaints in the same BLT performing a similar winter training exercise (0.16%). Blacks who had been raised in low-altitude regions were the most commonly afflicted. Prophylaxis with acetazolamide for subsequent altitude exposure can be recommended for those individuals identified as susceptible. Acute mountain sickness is not uncommon at intermediate altitudes.

Acetazolamide↗
PubMed2006

Endothelin-1 gene variants and levels associate with adaptation to hypobaric hypoxia in high-altitude natives.

High-altitude natives are adapted to hypobaric hypoxia, suggestive of genetic basis of adaptation. Since endothelin-1 (ET-1) is of prime importance in high-altitude disorders in sojourners, we envisaged the role of allelic variants of ET-1 in high-altitude adaptation. Four ET-1 polymorphisms, viz., (CT)(n)-(CA)(n) repeat, -3A/-4A, G2288T, and Lys198Asn, were investigated in 426 highlanders (HLs) and 236 lowlanders (LLs). The plasma ET-1 levels, SBP and BMI were significantly lower in the HLs than those in LLs (p<0.0001). The Longer-repeats (31-45), G allele, Longer-repeats/GG, and Longer-repeats/Lys198Lys combinations were overrepresented in the HLs (p<0.0001, p=0.03, p<0.0001, and p<0.0001, respectively). The Longer-repeats, -3A/-3A, GG and Lys198Lys genotypes associated with significantly lower ET-1 levels in the HLs (p<0.0001, p=0.001, p<0.0001, and p<0.0001, respectively). Combinations of Longer-repeats with -3A/-3A, GG, and Lys198Lys genotypes, and -3A/-3A/Lys198Lys combination revealed association with lower ET-1 levels in the HLs (p<0.001). The study reports over-representation of Longer-repeats, G allele, and wild-type genotype combinations in high-altitude natives. Interaction between these alleles and association with lower ET-1 levels strengthen their association with high-altitude adaptation. Presence of such alleles in sojourners may help in acclimatization.

Adaptation, Physiological↗
PubMedDate not supplied

Exercise-induced cerebral deoxygenation among untrained trekkers at moderate altitudes.

The pathophysiology of altitude-related disorders in untrained trekkers has not been clarified. In the present study, the effects of workload on cardiovascular parameters and regional cerebral oxygenation were studied in untrained trekkers at altitudes of 2700 m and 3700 m above sea level. We studied 6 males and 4 females at each altitude, and their average ages were 31.3+/-7.1 y at 2700 m and 31.2+/-6.8 y at 3700 m, respectively. The resting values of heart rate and mean blood pressure were not significantly different at 2700 m and 3700 m than at sea level. However, increases in these values after exercise were more prominent at high altitudes (heart rate increase = 51.6% at 2700 m and 70.4% at 3700 m; mean blood pressure increase: 19.0% at 2700 m and 17.2% at 3700 m). In addition, post-exercise blood lactate concentration was significantly higher at 3700 m than at sea level or at 2700 m (i.e., 7.6 mM at 3700 m, 3.8 mM at 2700 m, and 4.17 mM at 0 m, respectively). Exercise induced an acute reduction in the arterial oxygen saturation value (SpO2) at 2700 m and 3700 m (i.e., 11.2% reduction at 2700 m and 9.4% at 3700 m), whereas no changes were observed at sea level. The resting values of regional oxygen saturation (rSO2)--measured by a near infra-red spectrophotometer at sea level, 2700 m, and 3700 m-were nearly identical. Exercise at sea level did not reduce this value. In contrast, we observed a decrease in rSO2 after subjects exercised at 2700 m and 3700 m (i.e., 26.9% at 2700 m and 48.1% at 3700 m, respectively). The rSO2 measured 2 min and 3 min after exercise at 3700 m was significantly higher than the preexercise value. From these observations, we concluded that alterations in cardiovascular parameters were apparent only after an exercise load occurred at approximately 3000 m altitude. Acute reduction in cerebral regional oxygen saturation might be a primary cause of headache and acute mountain sickness among unacclimatized trekkers.

Acclimatization↗
PubMed2000

Italian high altitude laboratories: past and present.

Italy is a mountainous country with a total of 88 huts and bivouacs at altitudes higher than 3,000 m. Starting in the 19th century a great deal of research in high altitude pathophysiology has been carried out in Italy and many Italian physicians have been involved in mountain medicine. Most of the Italian research has been carried out at two locations: the scientific laboratories "Angelo Mosso" on Monte Rosa (Capanna Regina Margherita and Laboratorio Angelo Mosso), and the "Pyramid" in Nepal. The Capanna Regina Margherita, located on the top of Punta Gnifetti (Monte Rosa, 4,559 m), was inaugurated in 1893. With the support of Queen Margherita of Savoy, an Observatory for scientific studies was built beside this hut in 1894. In 1980 the hut was completely rebuilt by the Italian Alpine Club. The Istituto Angelo Mosso at Col d'Olen, at the base of Monte Rosa (at 2,900 m) was inaugurated in 1907. The high altitude laboratory named the "Pyramid" was built in 1990. Made of glass and aluminium, this pyramid-shaped structure is situated in Nepal at 5,050 m. The scientific laboratories "Angelo Mosso" on Monte Rosa (mainly the Capanna Regina Margherita) and the Pyramid form a nucleus for high altitude research: the former is especially devoted to research regarding acute mountain sickness and the response to subacute hypoxia, whereas the latter is a unique facility for research responses to chronic hypoxia, the effect of exposure to very high altitude, and the study of the resident population living in the Himalayas for at least 25,000 years.

Academies and Institutes↗