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PubMed2006

Persistent organic pollutants (POPs) as environmental risk factors in remote high-altitude ecosystems.

Persistent organic pollutants (POPs), and their transformation products, are the most investigated organic environmental contaminants within the past five decades. Organochlorines have been found in virtually all environmental compartments on the globe. Severe environmental implications have been shown to be associated with the presence of the POP group of contaminants in the environment. However, in the late 1990s, Canadian scientists first pinpointed the implication of POPs for high-altitude environments in a comprehensive way (Blais et al., 1998, Nature 395, 585-588). Under certain meteorological and geographic conditions, high-altitude environments can serve as "cold condensers" for atmospheric POP loadings. Subsequent investigations in high-altitude environments in Asia, Europe, and North and South America have confirmed suspicions that high-altitude mountainous regions have the potential to serve as focus regions for POPs and even for nonpersistent, medium-lived contaminants, such as "currently used pesticides", due to cold condensation and deposition in high altitudes. Although the presence and the altitude-dependent increase of POP levels in mountainous regions are confirmed by many international studies, the ecotoxicological consequences still remain largely unknown. At present, only a few studies have been published describing the biological effects in high-altitude environments due to increased POP exposure. Therefore, in this early stage of the international research effort on the ecotoxicological risk evaluation of persistent contaminants in high-altitude, pristine ecosystems, the present review intends to summarize the current state of research on POPs in high-altitude environments and draw preliminary conclusions on possible consequences of the presence of POPs in mountainous ecosystems based on currently available information from alpine and related Arctic environments.

Altitude↗
PubMed2006

Birth weight at high altitudes in Peru.

OBJECTIVE: To determine whether birth weights are lower at high altitudes, and whether gestational age at birth and a population's length of residence mitigate the effect of high altitude. METHODS: The birth weights of 84,173 neonates recorded in the Peruvian Perinatal Information System Database were analyzed between 1995 and 2002 for the cities of Lima (150 m), Huancayo (3280 m), Cuzco (3400 m), and Juliaca (3800 m). RESULTS: Birth weight was lower at high altitude, but there was no linear relation between altitude of residence and birth weight. Mean birth weight was higher in Juliaca than in Huancayo. There were no significant differences between the 4 cities regarding birth weights of infants born between 28 and 35 weeks of gestation. However, for infants born between 36 and 42 weeks, birth weight was lower at higher altitudes. This may be due to inadequate maternal oxygenation later in pregnancy at high altitude. In the multivariate analysis, after controlling for maternal age, marital status, parity, body mass index, pre-eclampsia or hemorrhage during pregnancy, and education, as well as sex of the newborn and gestational age at birth, birth weight was lower in all cities located at a higher altitude than Lima. Yet, longer residence at high altitudes may play a protective role. Juliaca (3800 m), where the population has resided the longest, had the lowest reduction in birth weight compared with Lima (150 m); Cuzco had intermediate values; and Huancayo (3280 m), where the population has resided the shortest, had the highest reduction in birth weight. CONCLUSIONS: Birth weight reduction, which is independent of socioeconomic factors, occurs only in births at term and may be less severe in populations that have resided longer at high altitudes.

Adolescent↗
PubMed2006

Flying high: a theoretical analysis of the factors limiting exercise performance in birds at altitude.

The ability of some bird species to fly at extreme altitude has fascinated comparative respiratory physiologists for decades, yet there is still no consensus about what adaptations enable high altitude flight. Using a theoretical model of O(2) transport, we performed a sensitivity analysis of the factors that might limit exercise performance in birds. We found that the influence of individual physiological traits on oxygen consumption (Vo2) during exercise differed between sea level, moderate altitude, and extreme altitude. At extreme altitude, haemoglobin (Hb) O(2) affinity, total ventilation, and tissue diffusion capacity for O(2) (D(To2)) had the greatest influences on Vo2; increasing these variables should therefore have the greatest adaptive benefit for high altitude flight. There was a beneficial interaction between D(To2) and the P(50) of Hb, such that increasing D(To2) had a greater influence on Vo2 when P(50) was low. Increases in the temperature effect on P(50) could also be beneficial for high flying birds, provided that cold inspired air at extreme altitude causes a substantial difference in temperature between blood in the lungs and in the tissues. Changes in lung diffusion capacity for O(2), cardiac output, blood Hb concentration, the Bohr coefficient, or the Hill coefficient likely have less adaptive significance at high altitude. Our sensitivity analysis provides theoretical suggestions of the adaptations most likely to promote high altitude flight in birds and provides direction for future in vivo studies.

Adaptation, Physiological↗
PubMedDate not supplied

The effect of altitude on radial keratotomy.

The authors analyzed refractive results of patients who underwent radial keratotomy (RK) at sea level and high altitude and evaluated the effects of the altitude. A total of 102 eyes undergoing RK procedures performed in two clinical centers having different altitude were analyzed. The results compared between subjects who had undergone RK at sea level (Istanbul/Turkey) and at an altitude of 5750 feet (Van/Turkey) were compared. Subjects were 19-42 years old with myopia from -4.00 to -12.00 diopters (D). The average preoperative spherical equivalent cycloplegic refractions (SECR) were -8.01 +/- 1.86 D and -6.99 +/- 2.15 D in the Istanbul and Van groups, respectively. These were divided into subgroups according to myopia degree and number of incisions and optic zone size. The RK procedures were performed by the same surgeon with diamond blade in standard Russian style. The average changes in SECR were 5.09 +/- 1.29 D and 6.50 +/- 2.24 D in subjects who had undergone RK at sea level and at 5750 feet, respectively. There was a significant difference between the subgroups (P < 0.0002). This difference was especially higher in the high myopia subgroups. Additionally, we obtained a partial relation between increase of RK incision number and SECR change at high altitude but not at sea level. No notable regression and progression were seen in the 3 months of follow-up at high altitude. These results support hypotheses suggesting both corneal hypoxic expansion in the area of RK incisions, which may lead to central corneal flattening, and barometric pressure directly altering corneal shape, which is responsible for the hyperopic shift induced by altitude. Ophthalmologists performing RK surgery at high altitude had better consider redesigning their RK nomograms in light of these findings. However, when the nomogram used at sea level was used at high altitude, the subjects became hyperopic.

Adult↗
PubMed2003

Sleep structure and periodic breathing in Tibetans and Han at simulated altitude of 5000 m.

Tibetans are the oldest population living permanently at high altitude. They possess several adaptations to low oxygen pressure that improve oxygen transport. We hypothesised that native Tibetans have mechanisms allowing them to maintain a better sleep structure and oxygenation during sleep at high altitude than newcomers from lower altitudes acclimatised to living at high altitude. We studied eight healthy young Tibetans, aged 26+/-7 years, and six healthy young Han aged 30.5+/-4 years. All subjects were living on the Tibetan plateau at an altitude of around 4000 m. Investigations were performed in Xining at an altitude of 2261 m, PB=581 mmHg. Two full polysomnographies (PSG) were performed in a hypobaric chamber, one at the ambient altitude, the second during acute exposure to the simulated altitude of 5000 m (PB=405 mmHg). Both PSG were done on the same night using split night design. At 2261 m no differences in sleep structure, breathing pattern during sleep or oxygenation were found, except a higher number of arousals and awakenings in Han (P<0.002). At 5000 m Tibetans had a longer sleep time (P=0.002), shorter stage 1 non-REM sleep (P<0.001) and longer stage 2 non-REM sleep than Han (P<0.001). Tibetans showed a trend to have more periodic breathing (PB) and higher mean arterial blood saturation than Han (NS). Our data suggest that Tibetans preserved better sleep structure and arterial blood oxygenation than Han during acute exposure to the simulated altitude of 5000 m.

Adult↗
PubMed2002

Cardiac morphology and function following long-term exposure to carbon monoxide at high altitude in rats.

Although chronic exposure to high altitude or carbon monoxide (CO) induces several cardiovascular adaptations in mammals, very little information is available on the cardiovascular effects due to exposure to these concomitant stresses. In particular, cardiac functional responses to chronic CO inhalation at high altitude has never been investigated. Thirty-two male Dark Agouti rats were exposed for 10 wk in steel chambers to (1) normoxic conditions (N rats), (2) 4000 m simulated high altitude (chronic hypobaric hypoxia, CH rats), (3) 50 ppm CO (CO rats), or (4) 50 ppm CO at 4000 m simulated high altitude (CH + CO rats). Left ventricular (LV) morphology and function were evaluated in normoxic conditions (1) using transthoracic Doppler echocardiography, just before as well as after exposure to environments, and (2) using transparietal intraventricular catheterisms following a short ventilatory-controlled thoracotomy (10 ml/kg volume inflow, pO2 ~159 torr) after exposure. Right ventricular (RV) function was evaluated using the same catheterism process after exposure. Body weight increased in all groups during exposure, but to a lesser extent in CH and CH + CO than in N and CO rats. At the end of exposure, hematocrit ratio was higher in CH than in CO rats, and in CH + CO than in CH rats. Carboxyhemoglobin levels were higher in CH + CO than in CO, CH, or N rats. Although neither a simulated high altitude nor CO alone had an effect on LV morphology and function, combined environments increased LV + septum weight, interventricular and posterior wall thicknesses, relative wall thickness, and LV systolic function. LV diastolic function was not altered by environmental conditions in the four groups. CO intensified the altitude-induced RV hypertrophy as well as the altitude-induced decrease in RV diastolic function. RV systolic function increased in CH rats, but adding CO did not amplify this adaptation process. Moreover, significant polynomial relationships were obtained between hematocrit ratio and LV + septum weight or left ventricular systolic pressure. Our results indicate that CO at high altitude induced severe hematological responses that could be involved in morphological and functional cardiac adaptations of both ventricles. Data indicate that CO at high altitude may be more detrimental to cardiac function than CO inhaled at sea level.

Altitude↗
PubMedDate not supplied

Morphological growth and thorax dimensions among Tibetan compared to Han children, adolescents and young adults born and raised at high altitude.

BACKGROUND: Studies comparing the growth of indigenous high-altitude Aymara children and children of low-altitude European descent who have been born and raised at high altitude in the Andes have provided evidence for genetically-determined differences in thorax growth, as well as for population differences in height, weight and other measures of overall size. Comparable studies now can be undertaken in Asia because of the growing number of Han Chinese who have been born and raised at high altitude on the Qinghai-Tibetan Plateau. AIM: The study compares the growth of indigenous Tibetan children and children of Han descent who have been born and raised at the same high altitudes, and under similar socio-economic conditions. SUBJECTS AND METHODS: Measurements of stature, sitting height, weight, triceps and subscapular skinfolds, upper arm muscle area, transverse chest diameter, anterio-posterior chest diameter, and chest circumference were taken on 1439 Tibetan and Han males and females between the ages of 6 and 29 years who were born and raised 3200 m, 3800 m or at 4300 m in the high altitude province of Qinghai in western China. RESULTS: Han-Tibetan differences in body size do not occur systematically for any measurement, for any age group, or for either gender; nor is there a systematic pattern of body size differences between 3200 m and 4300 m. This indicates that there are no differences in general growth between the two groups at high altitude in Qinghai, although both groups grow more slowly than urban children at low altitude in China. On the other hand, Tibetan males possess significantly deeper chests than Han males, and Tibetan females possess significantly wider chests than Han females. Tibetans of both sexes possess significantly larger chest circumferences than Han males and females. CONCLUSIONS: Although genetic similarities cannot be ruled out, comparable dietary stress is a likely explanation for the similar and slow morphological growth of Han and Tibetans at high altitude. However, Han-Tibetan differences in thorax dimensions are likely a consequence of population (genetic) differences in the response to hypoxia during growth.

Adolescent↗
PubMed2001

Human genetic adaptation to high altitude.

Some 140 million persons live permanently at high altitudes (>2500 m) in North, Central and South America, East Africa, and Asia. Reviewed here are recent studies which address the question as to whether genetic adaptation to high altitude has occurred. Common to these studies are the use of the oxygen transport system and the passage of time as organizing principles, and the recognition of the multifaceted ways in which genetic factors can influence physiological processes. They differ in terms of study approach and sources of evidence for judging duration of high altitude residence. Migrant, family set, and admixture study designs have been used for comparisons within populations. These collectively demonstrate the existence of genetic influences on physiological characteristics of oxygen transport. Differences in oxygen transport-related traits between Tibetan, Andean and European populations have been interpreted as having demonstrated the existence of genetic influences on high altitude adaptation but there is not consensus as to which groups are the best-adapted. Part of the controversy lies in the kinds of evidence used to assess duration of high altitude habitation. More other information is needed for a fuller appreciation of duration of residence and also features of population history (genetic drift, gene flow) but existing data are consistent with Tibetans having lived at high altitude longer than the other groups studied. Another issue surrounds usage of the term "adaptation." The definition should be based on evolutionary biology and physiological traits linked to indices of differential fertility and/or mortality. Two examples are developed to illustrate such linkages; intrauterine growth restriction (IUGR) at high altitude and the prevalence of Chronic Mountain Sickness (CMS). Interpopulational as well as intrapopulational variation exists in these conditions which appear linked to characteristics of oxygen transport. Both adversely influence survival and appear to be less severe (IUGR) or less common (CMS) among Tibetans than other groups. Thus available evidence suggest that Tibetans are better adapted. Needed, however, are studies which are better controlled for population ancestry, especially in South America, to determine the extent to which Tibetans differ from Andean highlanders. More precise information is also needed regarding the genetic factors underlying characteristics of oxygen transport. Such studies in Tibetan, Andean and Europeans as well as other high altitude populations offers a promising avenue for clarifying the adaptive value of physiological components of oxygen transport and the extent to which such factors differ among high altitude populations.

Acclimatization↗
PubMed2003

Fetal growth restriction and maternal oxygen transport during high altitude pregnancy.

High altitude reduces birth weights, averaging a 100-g fall per 1000 m elevation gain, as the result of restriction of third trimester fetal growth. Intrauterine growth restriction (IUGR) raises neonatal or infant mortality at low as well as at high altitude, but existing studies are unclear as to whether IUGR-specific mortality at high altitude is similar to, less than, or greater than at low altitude. Pregnancy increases maternal ventilation and raises arterial O(2) saturation at high altitude, which helps to protect against altitude-associated IUGR. Chronic hypoxia interferes with the maternal circulatory adjustments to pregnancy such that blood volume is lower and the rise in cardiac output diminished compared with sea level. The growth and remodeling of the uterine artery and other uteroplacental vessels is incomplete at high compared with low altitude, with the result that there is less redistribution of common iliac flow from the external iliac to the uterine arteries and lower uterine artery blood flow near term. Adaptations in multigenerational high altitude populations (e.g., Andeans and Tibetans) permit higher uterine artery blood flows and protect against altitude-associated IUGR.

Altitude↗
PubMed2025

Whole methylomes reveal high-altitude-associated methylation at hypoxia and pigmentation genes in South American Indigenous populations.

High-altitude adaptation in Andean populations has traditionally been studied through the lens of genetic variation, with limited exploration of epigenetic mechanisms such as DNA methylation. Here, we present the first whole-methylome data comparing Indigenous populations residing in high-altitude regions of the Ecuadorian Andes to those in low-altitude Peruvian Amazon regions bordering the Andes. By leveraging whole-methylome sequencing rather than methylation arrays, we achieved an unprecedented resolution of epigenetic variation, revealing novel insights into altitude-associated adaptations. We identified significant differentially methylated regions in genes involved in hypoxia response and skin pigmentation that differ from patterns previously observed in high-altitude Tibetan individuals [Lin et al. (Genome-wide DNA methylation landscape of four Chinese populations and epigenetic variation linked to Tibetan high-altitude adaptation. Science China Life Sciences 2023;66:2354-69. https://doi.org/10.1007/s11427-022-2284-8.)]. Our findings highlight the influence that altitude-specific environmental pressures, such as hypoxia and ultraviolet radiation, can have on the epigenetic landscapes observed between human populations. Importantly, we uncovered unique regulatory methylation signatures in the hypoxia response pathways of Andean populations, underscoring a distinct epigenetic trajectory compared to other high-altitude groups. This study represents a step forward in understanding Indigenous American genomic plasticity and demonstrates the value of whole-methylome data over methylation arrays in capturing the complex interplay between epigenetics and the environment. These results support a new approach to studying altitude plasticity and underscore the critical role of epigenetics in shaping population-specific cellular responses in Indigenous communities.

UV response↗
PubMed1995

Increased risk of craniosynostosis with higher antenatal maternal altitude.

BACKGROUND: During the 1980s, the Colorado Department of Health received reports from several high-altitude communities of clusters of the malformation craniosynostosis. In a population-based, case-control study, we examined the association between overall and trimester-specific maternal antenatal altitude exposure and the occurrence of infant craniosynostosis. METHODS: We identified case children through a statewide registry and randomly sampled control children from birth records. By telephone interview, each mother provided data on the locations of all antenatal residences and places of employment as well as other factors. Staff mapped all locations and abstracted the corresponding altitudes. RESULTS: The odds ratio (OR) of any synostosis for a time-weighted mean antenatal altitude of > or = 2000 metres (high altitude) versus < 2000 metres (low altitude) was 1.4 (lower bound of the one-sided 95% test-based confidence interval (CI): 0.9). The OR was elevated in smokers but not in non-smokers. As compared to non-smokers, the OR of any synostosis for high-altitude smokers was 4.6 (lower bound of the 95% one-sided exact CI: 1.7). Particularly elevated were the corresponding OR of coronal (18.1, 4.4) and metopic synostosis (16.3, 2.8), and OR for high-altitude exposure during the second trimester (any synostosis: 6.4, 1.99; coronal: 28.6, 6.1; metopic: 26.7, 4.1). CONCLUSIONS: Antenatal maternal high-altitude exposure and smoking are associated with increased risk of infant craniosynostosis, perhaps through generation of intermittent hypoxaemia.

Altitude↗
PubMed2004

New aspects of altitude adaptation in Tibetans: a proteomic approach.

A prolonged sojourn above 5500 m induces muscle deterioration and accumulation of lipofuscin in Caucasians, probably because of overproduction of reactive oxygen species (ROS). Because Sherpas, who live at high altitude, have very limited muscle damage, it was hypothesized that Himalayan natives possess intrinsic mechanisms protecting them from oxidative damage. This possibility was investigated by comparing the muscle proteomes of native Tibetans permanently residing at high altitude, second-generation Tibetans born and living at low altitude, and Nepali control subjects permanently residing at low altitude, using 2D gel electrophoresis and mass spectrometry. Seven differentially regulated proteins were identified: glutathione-S-transferase P1-1, which was 380% and 50% overexpressed in Tibetans born and living at high and low altitude, respectively; Delta2-enoyl-CoA-hydratase, which was up-regulated in both Tibetan groups; glyceraldehyde-3-phosphate dehydrogenase and lactate dehydrogenase, which were both slightly down-regulated in Tibetans born and living at high altitude; phosphoglycerate mutase, which was 50% up-regulated in the native Tibetans; NADH-ubiquinone oxidoreductase, slightly overexpressed in Tibetans born and living at high altitude; and myoglobin, which was overexpressed in both Tibetan groups. We concluded that Tibetans at high altitude, and to some extent, those born and living at low altitude, are protected from ROS-induced tissue damage and possess specific metabolic adaptations.

Adaptation, Physiological↗
PubMed1999

Marathons in altitude.

PURPOSE: We examined the effect of altitude up to 5200 m on marathon (42,195 m) performances. METHODS: Eight elite and four good runners participated in a marathon at 4300-m altitude (A1), and five elite runners participated both in A1 and in a marathon at 5200-m altitude (A2). The maximal aerobic power (VO2max) was determined indirectly in altitude during A1 and A2 expeditions from the scores of a 12-min running test. The fractions of VO2max utilized during both races were calculated from the linear relationship between running speed and VO2 described by Costill and Fox (1969). RESULTS: VO2max significantly decreases with altitude (P<0.001). We found a linear relationship (R2 = 0.73, P<0.001) between the speed of each participant in the sea level marathon and the speed of A1. The mean difference between the sea level and the A1 speed was 35+/-9% (P<0.001). In A1, elite runners utilized 63+/-8% whereas good runners utilized 52+/-8% of VO2max (P<0.001). The five elite runners utilized 74+/-6%; 67+/-1% (P< 0.01), and 71+/-3% (P<0.01) of their VO2max at sea level, A1, and A2, respectively. In Al, the mean heart rate (HR) was higher in elite than in good runners (P<0.001), whereas the percentage of maximum theoretical HR was 83+/-3% and 81+/-5%, respectively (P>0.05). CONCLUSIONS: Marathon performance in altitude is mainly affected by the lower VO2max. The better performance of elite marathoners in altitude compared with good runners was related to the higher % of VO2max maintained during every marathon. The differences between the expected and the observed performances at high altitude depend on the uneven running path and on a poorer economy of running that is related to the higher mechanical work of breathing. The fractional utilization of VO2max seems lowered by acute exposure to altitude and slightly increases with acclimatization.

Adult↗
PubMed1997

The effect of altitude hypoxia on glucose homeostasis in men.

1. Exposure to altitude hypoxia elicits changes in glucose homeostasis with increases in glucose and insulin concentrations within the first few days at altitude. Both increased and unchanged hepatic glucose production (HGP) have previously been reported in response to acute altitude hypoxia. Insulin action on glucose uptake has never been investigated during altitude hypoxia. 2. In eight healthy, sea level resident men (27 +/- 1 years (mean +/- S.E.M); weight, 72 +/- 2 kg; height, 182 +/- 2 cm) hyperinsulinaemic (50 mU min-1 m-2), euglycaemic clamps were carried out at sea level, and subsequently on days 2 and 7 after a rapid passive ascent to an altitude of 4559 m. 3. Acute mountain sickness scores increased in the first days of altitude exposure, with a peak on day 2. Basal HGP did not change with the transition from sea level (2.2 +/- 0.2 mg min-1 kg-1) to altitude (2.0 +/- 0.1 and 2.1 +/- 0.2 mg min-1 kg-1, days 2 and 7, respectively). Insulin-stimulated glucose uptake rate was halved on day two compared with sea level (4.5 +/- 0.6 and 9.8 +/- 1.1 mg min-1 kg-1, respectively; P < 0.05), and was partly restored on day 7 (7.4 +/- 1.4 mg min-1 kg-1; P < 0.05 vs. day two and sea level). Concentrations of glucagon and growth hormone remained unchanged, whereas glucose, C-peptide and cortisol increased on day 2. Noradrenaline concentrations increased during the stay at altitude, while adrenaline concentrations remained unchanged. In response to insulin infusion, catecholamines increased on day 2 (noradrenaline and adrenaline) and day 7 (adrenaline), but not at sea level. 4. In conclusion, insulin action decreases markedly in response to two days of altitude hypoxia, but improves with more prolonged exposure. HGP is always unchanged. The changes in insulin action may in part be explained by the changes in counter-regulatory hormones.

Acclimatization↗
PubMed2005

Cerebrovascular responses to hypoxia and hypocapnia in high-altitude dwellers.

Cerebral blood flow is known to increase in response to hypoxia and to decrease with hypocapnia. It is not known, however, whether these responses are altered in high-altitude dwellers who are not only chronically hypoxic and hypocapnic, but also polycythaemic. Here we examined cerebral blood flow responses to hypoxia and hypocapnia, separately and together, in Andean high-altitude dwellers, including some with chronic mountain sickness (CMS), which is characterized by excessive polycythaemia. Studies were carried out at high altitude (Cerro de Pasco (CP), Peru; barometric pressure (P(B)) 450 mmHg) and repeated, following relief of the hypoxia, on the day following arrival at sea level (Lima, Peru; P(B) 755 mmHg). We compared these results with those from eight sea-level residents studied at sea level. In nine high-altitude normal subjects (HA) and nine CMS patients, we recorded middle cerebral artery mean blood flow velocity (MCAVm) using transcranial Doppler ultrasonography, and expressed responses as changes from baseline. MCAVm responses to hypoxia were determined by changing end-tidal partial pressure of oxygen (P(ET,O2)) from 100 to 50 mmHg, with end-tidal partial pressure of carbon dioxide clamped. MCAVm responses to hypocapnia were studied by voluntary hyperventilation with (P(ET,O2)) clamped at 100 and 50 mmHg. There were no significant differences between the cerebrovascular responses of the two groups to any of the interventions at either location. In both groups, the MCAVm responses to hypoxia were significantly greater at Lima than at CP (HA, 12.1 +/- 1.3 and 6.1 +/- 1.0%; CMS, 12.5 +/- 0.8 and 5.6 +/- 1.2%; P < 0.01 both groups). The responses at Lima were similar to those in the sea-level subjects (13.6 +/- 2.3%). The responses to normoxic hypocapnia in the altitude subjects were also similar at both locations and greater than those in sea-level residents. During hypoxia, both high-altitude groups showed responses to hypocapnia that were significantly smaller at Lima than at CP (HA, 2.17 +/- 0.23 and 3.29 +/- 0.34% mmHg(-1), P < 0.05; CMS, 1.87 +/- 0.16 and 3.23 +/- 0.24% mmHg(-1); P < 0.01). The similarity of the results from the two groups of altitude dwellers suggests that haematocrit is unlikely to greatly affect cerebrovascular reactivity to hypoxia and hypocapnia. The smaller vasodilatation to hypoxia and larger vasoconstriction to hypoxic hypocapnia at high altitude suggest that cerebrovascular responses may be impaired at the high altitude, i.e. a maladaptation. The changes in the responses within less than 24 h at sea level indicate that this impairment is rapidly reversible.

Acclimatization↗
PubMed1980

Calcium augments hypoxic vasoconstriction in lungs from high-altitude rats.

Isolated lungs from high-altitude rats compared with those from low-altitude rats have blunted hypoxic pressor responses. Because calcium is essential for the hypoxic pressor response and has been shown to be altered in the pulmonary arterial smooth muscle during high-altitude exposure, we wondered whether altered calcium metabolism might account for the blunted response. We attempted to unmask differences between high- and low-altitude rat lungs by altering extracellular calcium. The addition of calcium to the blood perfusate augmented the hypoxic pressure response of high-altitude lungs and depressed that of low-altitude lungs. Calcium addition did not affect pressor responses to angiotensin II, but slowed vasodilation after both angiotensin injection and removal of the hypoxic stimulus. The maximal KCl-induced contraction was blunted in rings of main pulmonary artery from high-altitude rats, but augmented in their aortic rings. Submaximally constricted (40 mM KCl) pulmonary arteries from low- but not high-altitude rats further constricted with calcium addition. Aortic rings exhibited an inverse behavior. Thus, calcium addition augmented the blunted vasopressor response in high-altitude rats lungs, possibly by an effect on lung arteries. The aorta and main pulmonary artery differ in calcium handling.

Adaptation, Physiological↗
PubMed1985

Low P50 in deer mice native to high altitude.

Whereas it is widely believed that animals native to high altitude show lower O2 partial pressures at 50% hemoglobin saturation (P50) than do related animals native to low altitude, that "fact" has not been well documented. Consequently, P50 at pH 7.4, PCO2(7.4), the CO2 Bohr effect, and the buffer slope (delta log PCO2/delta pH) were determined via the mixing technique in Peromyscus maniculatus native to a range of altitudes but acclimated to 340 or 3,800 m. PCO2(7.4) and buffer slope were substantially lower at high altitude. The change in P50(7.4) between acclimation altitudes was minimal (0.8% increase at 3,800 m), because of counterbalancing changes in PCO2, 2,3-diphospho-D-glycerate concentration, and perhaps other factors. At both acclimation altitudes there was a highly significant negative correlation between P50(7.4) and native altitude. Since pH in vivo probably increases slightly at high altitude, the data on P50 corrected to pH 7.4 are probably underestimates of the difference in in vivo P50 at low vs. high altitude. Hence these results corroborate theoretical predictions that low P50 is advantageous under severe hypoxic stress.

Acclimatization↗
PubMed1990

Systemic vascular reactivity during high-altitude pregnancy.

There is an increased incidence of preeclampsia at high compared with low altitude. Increased vasoreactivity, possibly due to a deficiency of vasodilator prostaglandins, is thought to contribute to the etiology of preeclampsia. We sought to determine whether high-altitude exposure increased systemic vascular reactivity during pregnancy. We measured systemic vascular reactivity and contractile sensitivity of isolated aortic rings from pregnant and nonpregnant guinea pigs kept for 6 wk at either simulated high altitude (3,900 m) or low altitude (1,600 m). We found that pregnancy at high compared with low altitude increased baseline systemic vascular resistance (SVR) but not the SVR response to angiotensin II in awake unstressed guinea pigs. Contractile sensitivity to norepinephrine was also increased in aortic rings isolated from high-altitude compared with low-altitude pregnant animals. Meclofenamate, a prostaglandin synthesis inhibitor, did not equalize vasoreactivity in the high- and low-altitude pregnant guinea pigs or in their isolated aortic rings. We concluded that pregnancy at high compared with low altitude increased base-line SVR and aortic contractile sensitivity but that mechanisms other than decreased vasodilator prostaglandin production were responsible.

Altitude↗