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Aldosterone, cortisol, and electrolyte responses to hypobaric hypoxia in moderate-altitude natives.

Serum aldosterone, cortisol, and electrolyte concentration, and urinary aldosterone and electrolyte excretion responses were examined in seven low-altitude natives (LAN) (373 m or less, aged 19-25 yr) and nine moderate-altitude natives (MAN) (1,830-2,200 m, aged 19-23 yr) for 2 d at their own residence (home) altitude (PB 740 or 585 mm Hg, respectively) and later for 2 d during decompression at a simulated altitude of 4,270 m (PB 447 mm Hg). The LAN group demonstrated higher (p less than 0.05) serum cortisol concentrations and respiration rates, and lower (p less than 0.05) serum aldosterone and potassium, and urinary aldosterone, sodium, and potassium concentrations at certain times during decompression compared to their home responses. Moderate-altitude native responses, on the other hand, were generally unchanged. Manifestations of acute mountain sickness at PB 447 mm Hg were also significantly greater in the LAN group. Thus, it appears that the MAN subjects were influenced less by the drop in ambient oxygen tension associated with PB 447 mm Hg.

Acute Disease↗

High-altitude pulmonary edema among visitors to Summit County, Colorado.

Twenty-nine cases of high-altitude pulmonary edema (HAPE) affecting visitors to Summit County, Colorado, were analyzed. The mean age of the group was 37.8 years, and all the patients were male. These results differ from previous studies and suggest that there are two varieties of HAPE. The first type (type 1, or nonresident-ascent HAPE) affects visitors to altitudes above 8,000 ft (2,439 m). At altitudes up to 11,000 ft (3,354 m), it is a disease that affects primarily adult men. The second variety (type 2, or resident-reascent HAPE) affects residents of high altitudes when they descend to an elevation below 8,000 ft (2,430 m) and then return to high altitude. This type of HAPE affects male and female residents almost equally and is a disease of childhood and adolescence.

Adult↗

Sea-level physical activity and acute mountain sickness at moderate altitude.

The effect of previous physical conditioning on young well-conditioned mountaineers in relationship to acquiring acute mountain sickness is controversial. Data show both increased and decreased effects on the incidence of altitude illness. How general tourists at moderate altitudes are affected is unknown. To determine the influence of sea-level habitual physical activity on the incidence of mountain sickness, we surveyed 205 participants in a scientific conference at 3,000 m (9,840 ft). A 36-item questionnaire was distributed to the subjects 48 hours after arrival at altitude. Their sea-level physical activity (SLPA) was measured by a published and validated instrument that included questions about patterns of work, sporting, and leisure-time activities. Acute mountain sickness was defined as the presence of 3 or more of the following symptoms: headache, dyspnea, anorexia, fatigue, insomnia, dizziness, or vomiting. Most of the respondents were male (62%) from sea level (89%) with a mean age of 36 +/- 8.7 (standard deviation) years (range, 22 to 65). Nearly all (94%) were nonsmokers, and 28% had acute mountain sickness. The mean SLPA score was 8.0 +/- 1.3 (range, 5.1 to 12.0). No statistically significant difference in mean SLPA scores was found between those with and without acute mountain sickness (8.1 versus 7.8), nor in the individual indices (work, 2.5 versus 2.4; sport, 2.9 versus 2.7; leisure, 2.8 versus 2.7). We conclude that habitual physical activity performed at sea level does not play a role in the development of altitude illness at moderate altitude in a general tourist group.

Acute Disease↗

Perceived exertion during hypobaric hypoxia in low- and moderate-altitude natives.

Ratings of perceived exertion (RPE) were examined in six low- (LAN) and eight moderate- (MAN) altitude natives during exercise at their residence (home) altitude (366 m and 2,200 m, respectively) and 1-4 wk later following 2-d decompression to 4,270 m (447 mm Hg). Cardiorespiratory, plasma lactate, and differentiated RPE measures were obtained at exercise intensities representing 35, 55, 75, 85, and 100% VO2peak. In general, cardiorespiratory and plasma lactate values were similar in LAN and MAN at their residence altitudes and during hypobaric hypoxia. However, the decrease in VCO2 was greater (P < 0.05) in LAN than MAN. At their residence altitudes, both LAN and MAN reported local RPE values that were greater (P < 0.05) than central ratings at the moderate to high exercise intensities. At 447 mm Hg, central and local RPE were similar in LAN. However, there was a significant correlation between acute mountain sickness (AMS) symptoms and central RPE (r = 0.875) across the five exercise intensities in LAN. The differences between the central and local RPE noted in MAN during their residence testing also persisted at 447 mm Hg. Thus, differentiated ratings of perceived exertion were similar in MAN at their residence altitude and at 4,270 m, but not in LAN subjects. Several factors, including AMS, may have contributed to this group difference in the RPE response.

Adult↗

[High altitude sojourn in lung diseases].

Patients with pulmonary diseases and reduced respiratory reserves live 'higher' than healthy persons. Nevertheless, they tolerate staying at medium altitudes ranging between 1500 and 2500 m a.s.l. surprisingly well. In order to establish patients' high-altitude fitness, it is necessary to examine them individually. It is important to differentiate between reversible obstructive and irreversible pulmonary diseases. Despite a drop in arterial oxygen pressure and oxygen saturation, many patients suffering from average obstructive illness feel no discomfort at high altitude and are surprisingly fit. Patients with irreversible pulmonary diseases, pulmonary emphysema or pulmonary fibrosis feel often more comfortable in the mostly drier and cooler mountain air; however, they are physically less fit when compared at lower altitudes. In contrast to the reversible obstructive pulmonary diseases, only slight adaptation is possible. In judging the tolerance to high altitude, one has to consider that a large number of patients suffering from chronic obstructive pulmonary illnesses simultaneously suffer from coronary heart diseases.

Acclimatization↗

Integrated Cytokine and Immune Cell Profiling Reveals a Distinct Immune Signature Associated with High-Altitude Pulmonary Edema.

High-altitude pulmonary edema (HAPE) is a rapidly progressive, life-threatening disorder arising in otherwise healthy individuals upon ascent to high altitude, yet the mechanisms underlying maladaptive vascular leak remain poorly defined. Although elevated pulmonary arterial pressure and capillary stress failure are recognized as central hemodynamic drivers, accumulating evidence indicates that innate immune dysregulation is an equally critical, largely unexplored determinant of HAPE. To systematically delineate the immune and molecular programs that distinguish pathological responses to hypobaric hypoxia from acclimatization, peripheral blood along with clinical details was collected from low-altitude controls (LA-Cntrl, number of participants, (n = 19), healthy high-altitude sojourners (HA-Cntrl, n = 47), and HAPE patients (n = 90). Plasma proteomic markers were quantified using a targeted panel, while monocyte and dendritic cell subsets in peripheral blood mononuclear cells were immunophenotyped by multicolor flow cytometry. HA-Cntrl subjects displayed an anti-inflammatory profile, marked by the suppression of CXC chemokine receptor 3 axis chemokines. HAPE patients, in contrast, exhibited a pro-inflammatory, vascular injury signature, with elevated levels of inflammatory interleukins and myeloid and chemotactic factors. This inflammatory signature was accompanied by the expansion of classical monocytes, implicating a myeloid vascular program associated with HAPE.

Humans↗

Cerebrovascular stroke at high altitude.

OBJECTIVE: To asses the high altitude as a risk factor for cerebrovascular stroke in people residing at a height greater than 15,000 feet above sea level. DESIGN: A case control study. PLACE AND DURATION OF STUDY: The study was conducted at Military Hospital, Rawalpindi from June 2000 to May 2001. PATIENTS AND METHODS: Four thousand persons between the ages of 20-40 years, residing at the height of 15,000 feet or above, were studied for occurrence of stroke. All cases of stroke referred from Northern areas of Pakistan, with positive CT scan, were included in the study. They were then investigated at Military Hospital, Rawalpindi to find out any other risk factor for stroke. During the same period four thousand persons living at Rawalpindi (height-2,000 ft) in same age group were also observed as control group. RESULTS: Ten patients suffered from stroke at high altitude while just one case had stroke in indexed age group at lower heights (p-value<0.05). Relative risk was 10 times greater at high altitude. CONCLUSION: High altitude is a risk factor for stroke in persons residing at altitudes of over 15,000 ft.

Adult↗

Hemoglobin concentration of high-altitude Tibetans and Bolivian Aymara.

Elevated hemoglobin concentrations have been reported for high-altitude sojourners and Andean high-altitude natives since early in the 20th century. Thus, reports that have appeared since the 1970s describing relatively low hemoglobin concentration among Tibetan high-altitude natives were unexpected. These suggested a hypothesis of population differences in hematological response to high-altitude hypoxia. A case of quantitatively different responses to one environmental stress would offer an opportunity to study the broad evolutionary question of the origin of adaptations. However, many factors may confound population comparisons. The present study was designed to test the null hypothesis of no difference in mean hemoglobin concentration of Tibetan and Aymara native residents at 3,800-4,065 meters by using healthy samples that were screened for iron deficiency, abnormal hemoglobins, and thalassemias, recruited and assessed using the same techniques. The hypothesis was rejected, because Tibetan males had a significantly lower mean hemoglobin concentration of 15.6 gm/dl compared with 19.2 gm/dl for Aymara males, and Tibetan females had a mean hemoglobin concentration of 14.2 gm/dl compared with 17.8 gm/dl for Aymara females. The Tibetan hemoglobin distribution closely resembled that from a comparable, sea-level sample from the United States, whereas the Aymara distribution was shifted toward 3-4 gm/dl higher values. Genetic factors accounted for a very high proportion of the phenotypic variance in hemoglobin concentration in both samples (0.86 in the Tibetan sample and 0.87 in the Aymara sample). The presence of significant genetic variance means that there is the potential for natural selection and genetic adaptation of hemoglobin concentration in Tibetan and Aymara high-altitude populations.

Adaptation, Physiological↗

Carotid body tumors in inhabitants of altitudes higher than 2000 meters above sea level.

BACKGROUND: Carotid body tumors (CBTs) are rare. Diagnosis is usually delayed until the tumors reach a critical volume and a mass appears in the neck, which is often asymptomatic. METHODS: We reviewed retrospectively the cases with CBT diagnosed from 1965 to 1995 in the Hospital de Oncologia in Mexico City with inhabitants at an altitude higher than 2200 m above sea level to see whether these tumors have the same characteristics as those of inhabitants of countries of lower altitudes. We reviewed the clinical features, diagnostic procedures, therapy, results, and complications. RESULTS: There were 120 CBT cases, which represent 79% of the parapharyngeal space tumors diagnosed at our hospital; 116 (96%) were benign and 4 (3.3%) were malignant. Women predominated (89%), and the female-male ratio was 8.3:1. Five patients had multiple paragangliomas, and one had a family history of CBT. Eighty patients (66%) underwent surgery. This was done by cervical approach in 78 cases (97%), and 2 (2.5%) required additional mandibulotomy. There were three deaths due to brain ischemia after carotid ligature. Forty-one patients were followed without treatment, due to advanced age, concomitant diseases, or great volume of the tumor. Median follow-up of these patients was 47 months, during which time no patient reported additional symptoms, accelerated enlargement of the tumor, or metastasis. With a median follow-up of 54 months, only one patient developed local recurrence and three patients developed distant metastasis. CONCLUSIONS: We conclude that cases of CBT in our high-altitude population differ significantly from those cases in inhabitants of cities in the U.S. or Europe of less than 1500 m above sea level. Those of high altitudes have an evident female predominance (8.3:1), low rate of bilaterality (5%), and a family history of 1% versus a discrete female predominance (2:1), bilaterality from 10% to 20%, and family history from 7% to 25% in low altitudes. When adequate criteria are used to determine surgical resectability, a complete resection is achieved in 85% of cases, with low or null mortality and high local control.

Adult↗

Expression of Fos immunoreactivity in some catecholaminergic brainstem neurons in rats following high-altitude exposure.

This study examined the response of neurons of the cardiorespiratory centers, i.e., the nucleus tractus solitarius and the ventrolateral medulla as well as the area postrema in adult and postnatal rats subjected to high-altitude exposure at 4,000 m and 8,000 m. In adult control rats, sporadic Fos-positive neurons were detected in the above-mentioned areas. On exposure to 4,000 m altitude, the number of Fos-positive neurons was noticeably increased. At 8,000 m, the incidence of labeled cells was markedly increased, with many of them doubly labeled for tyrosine hydroxylase. In postnatal rats, Fos expression was not detected in these areas in either control rats or rats exposed to 4,000 m altitude. Fos-positive cells, however, were observed in the these areas in postnatal rats exposed to 8,000 m. In the latter, tyrosine hydroxylase labeling was observed in some Fos-positive cells in the nucleus tractus solitarius and ventrolateral medulla. In rats killed at 24 hr after exposure to high altitude, Fos expression in both the adult and the postnatal rats was comparable to that in their corresponding control rats. Present results suggest that Fos expression in various brainstem areas was induced by reduced oxygen tension in the ambient air at high altitude. Double labeling of some Fos-positive neurons with tyrosine hydroxylase indicates an increased sympathetic activation, which may be involved in the mediation of cardiorespiratory responses to hypoxia. This, however, was less evident in the postnatal animals. It is possible that the peripheral chemoreceptors or the regulation of autonomic functions is not fully developed in this age group.

Altitude Sickness↗

Altitude, heredity and body proportions in northern Chile.

Recent studies of the effects of hypoxia on human growth and adult size have focused mainly on the variability of single measurements. In this paper we explore changes with altitude and ethnicity (Spanish-Aymara ancestry) in body proportions of permanent residents of an altitudinal gradient (0-4000 meters) in northern Chile. Body proportion or shape is assessed by anthropometric indices and principal components of 14 bone measurements. Ethnicity independent of altitude had its major effect on proportions and a lesser effect on size. Aymara had larger relative sitting heights, broader builds and prominent facial development as compared to non-Aymara (Spanish). Altitude also affected head and chest proportions during growth. On the whole, the effects of altitude and Aymara ancestry on the measurements and indices were independent (not necessarily of similar direction or magnitude), in spite of a correlation of ethnicity and altitude in Andean populations.

Adolescent↗

Optimal birthweights in Peruvian populations at high and low altitudes.

This study tests the hypothesis that optimum birthweight for survival is lower among hospital-born infants in Puno, Peru (altitude 3860 m) than that among their counterparts at low altitude in Tacna, Peru (altitude 600 m). The data are derived from hospital birth records for 1971 and 1972 and municipal death records for 1971 through 1973. Linking these records permits analysis of the patterns of mortality in relation to birthweight. Stabilizing selection upon birthweight is operating in both populations. The high altitude population has a lower mean birthweight and a lower optimal birthweight. The Puno population is closer to its optimal birthweight distribution and, as a result of mortality during infancy, is approaching its optimum birthweight distribution for survival more rapidly than the Tacna population. It appears that the high altitude Puno population may well be adapted to its environment in the sense that there is less selective mortality on birthweight phenotypes.

Altitude↗

Altitude and infant growth in Bolivia: a longitudinal study.

The growth of 79 healthy, well-nourished lowland (400 M) and highland (3600 M) Bolivian infants was analyzed in a longitudinal study through the first postnatal year. Compared to low altitude infants, the high altitude infants were found, by analysis of covariance controlling for size at the previous exam, to be significantly shorter at birth, 1 and 6 months, while they were significantly lighter only at birth and 1 year. Recumbent length gain was slower in the high altitude infants in the early months of life, while weight gain did not differ between altitudes. The observed lower weights at high altitude throughout the first year appear to be due to a persistence of lower weights seen at birth and not to postnatal growth retardation. Significantly greater triceps and subscapular skinfold thickness measurements were found in the highland group, despite their smaller length and weight. The possible causes and implications of the greater fat accumulation in the highland infants are discussed.

Altitude↗

Neonatal size and infant mortality at high altitude in the western Himalaya.

A prospective study was undertaken in Ladakh, India, a high-altitude region of the Himalaya, to investigate the effects of small average birth size on neonatal mortality. While such studies exist from high-altitude regions of the New World and shed light on the adaptive status of high-altitude-dwelling populations there, this is the first to examine this relationship in the Himalaya. In a sample of 168 newborns, birthweight and other anthropometric measurements were reduced relative to Andean and Tibetan newborns. Logistic regression and hazard analysis showed that neonatal biological characteristics such as weight, fatness, and circumferences were important predictors of survival probabilities of infants, especially in the neonatal period. Low Rohrer's Ponderal Index (PI) was particularly strongly related to poor survival outcome. Males and females showed no significant differences in mortality risk. Data derived from reproductive histories revealed that neonatal mortality accounted for 70-80% of total infant mortality in Ladakh. Compared to other high-altitude studies, small newborn size in Ladakh was associated with much higher mortality risks; mortality risk rose dramatically with birthweights below the mean (2,764 grams), which characterized 50% of all newborns. It is argued that newborns in Ladakh are subject to strong directional selective forces that favor higher birthweights that incur lower risks of neonatal mortality, while Andean infants are subject to relatively mild selection pressure at both ends of the birthweight distribution. Given the overall small size at birth of Ladakhi newborns and the poor survival outcomes of newborns below the mean, it is suggested that this population is less well adapted in a biological sense to the stresses inherent in this high-altitude environment than are Andean populations, perhaps due to the relatively recent colonization of the area and the substantial genetic admixture that has occurred in the past.

Altitude↗

Reduction of I(Ca,L) and I(to1) density in hypertrophied right ventricular cells by simulated high altitude in adult rats.

The present paper describes the effect of a simulated hypobaric condition (at the altitude of 4500 m) on morphological characteristics and on some ionic currents in ventricular cells of adult rats. According to current data, chronic high-altitude exposure led to mild right ventricular hypertrophy. Increase in right ventricular weight appeared to be due wholly or partly to an enlargement of myocytes. The whole-cell patch-clamp technique was used and this confirmed, by cell capacitance measurement, that chronic high-altitude exposure induced an increase in the size of the right ventricular cells. Hypertrophied cells showed prolongation of action potential (AP). Four ionic currents, playing a role along with many others in the precise balance of inward and outward currents that control the duration of cardiac AP, were investigated. We report a significant decrease in the transient outward (I(to1)) and in the L-type calcium current (I(Ca,L)) densities while there was no significant difference in the delayed rectifier current (I(K)) or in the inward rectifier current (I(K1)) densities in hypertrophied right ventricular cells compared to control cells. At a given potential the decrease in I(to 1) density was relatively more important than the decrease in I(Ca,L) density. In both cell types, all the currents displayed the same voltage dependence. The inactivation kinetics of I(to 1) and I(Ca,L) or the steady-state activation and inactivation relationships were not significantly modified by chronic high-altitude exposure. We conclude that chronic high-altitude exposure induced true right ventricular myocyte hypertrophy and that the decrease in I(to 1) density might account for the lengthened action potential, or have a partial effect.

Action Potentials↗

Cardiopulmonary functional changes in acute acclimatisation to high altitude in mountaineers.

Simple cardiopulmonary functions were studied serially in 26 mountaineers between sea level and an altitude of 25,200 ft. Up to 12,000 ft there was no altitude sickness, though there were complaints of leech bite (26.9%) and blisters (3.8%). One member died of exhaustion, two developed pulmonary oedema, one "flu" (at 15,600 ft) and one pleural rub (at 21,000 ft). Up to 16,000 ft altitude, 4 to 7.7% developed diarrhoea or epistaxis only, but at higher levels 25 to 50% subjects developed several symptoms, besides excessive dyspnea. These included diarrhoea (35-60%), vomiting (30%) abdominal pain (35-60%), rectal bleeding (15%), chest pain (10-40%), dry cough (40-60%), giddiness (30%) and poor memory (7.7%). A small rise in blood pressure was seen (for systolic at lower and diastolic at greater altitudes). After 18,200 ft the steady increase seen in VE slowed and the rise in heart rate and respiratory rate (f) became steeper. After a small rise at 7,800 ft, FVC and FEV1 showed a gradual decline at higher altitudes. After a large initial increase in PEFR up to 12,000 ft, a gradual decline was seen. The mean weight loss during the expedition was 8 +/- 2.7 kg. These changes seem to be due to an incomplete acclimatisation, which future mountaineering teams should take into consideration to avoid health problems and improve performance.

Acclimatization↗

Elevated nocturnal blood pressure assessed by ambulatory automatic monitoring during a stay at high altitude.

The aim of this study was to explore, in healthy children, the arterial blood pressure response to a 3-week stay at high altitude (4200 m). An auscultatory automatic ambulatory pressuremeter was used to avoid undue environmental influence on the measurement. The blood pressure was monitored three times in a group of ten boys, aged 10.5 (CI 0.9 years): at sea level (control values), at an altitude of 2100 m after at least 24 h of acclimatization and after at least 24 h at 4200 m altitude. Each period of monitoring extended over 24 h with 10-min intervals between successive measurements. Arterial blood pressure was evaluated separately for the night and day periods. Nocturnal recordings revealed an increase with altitude in systolic as well as in the diastolic blood pressure. Because of the technique used to gather data, this is thought to have represented an independent effect of altitude without interference from the medical environment or diurnal activity.

Acclimatization↗

Similarity of PO2 and PCO2 values in the air cell of eggs of birds and in the alveolar gas of humans at sea level and at high altitude.

At the end of incubation, the partial pressures of oxygen and carbon dioxide in the air cell of sea-level avian eggs are similar to those in the expiratory air of adult birds. At high altitude, changes in the permeability of the shell and probably in the embryo metabolism partially compensates the increase in the gas diffusion constant resulting from the low barometric pressure. The aim of this study was to test whether--despite of the adaptive responses of the high altitude avian embryo--the air cell values would be similar to those of the alveolar air of high altitude human natives. Air cell O2 (48.3 +/- 1.6 torr) and CO2 (20.9 +/- 0.85 torr) pressure values were obtained by studying naturally incubated eggs of the Andean gull (Larus serranus) at 4650 m. Sea-level chicken (Gallus gallus) air cell pressure values of O2 (102.3 +/- 2.7 torr) and of CO2 (43.3 +/- 1.3 torr) were obtained from the literature for comparison. Both these values were similar to those found in the alveolar air of humans at sea level (O2: 104.4 +/- 0.4 torr, CO2: 40.1 +/- 0.25 torr) and at high altitude (4540 m) (O2: 50.5 +/- 0.53 torr, CO2: 29.1 +/- 0.37 torr). Despite very large evolutionary changes in morphology and physiology of the respiratory organs, the head pressure of O2 that oxygenates the blood keeps a constant value in the pre-pipping avian embryo and in the alveolar air of adult mammals. This constancy holds valid at high altitude.

Altitude↗