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Adaptations of the antioxidant system in erythrocytes of trained adult rats: impact of intermittent hypobaric-hypoxia at two altitudes.

We have investigated the effects of daily exposure to intermittent hypobaric-hypoxia to two simulated altitudes (5700 m and 6300 m) in adult male rats that had been regularly swim trained in normoxia at sea level prior to exposures. Superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) along with the oxidative stress (OS) indices, malondialdehyde (MDA) and protein carbonyl content were measured in erythrocytes and their membranes. Hemoglobin increased in the trained animals exposed to 5700 m and in untrained rats exposed to 6300 m. Osmotic fragility in terms of hemolysis increased in altitude exposed animals. SOD increased in those exposed to 6300 m, while CAT increased in trained rats exposed to 5700 m and to 6300 m unlike in untrained rats where CAT increased only at 6300 m. GSH-Px showed varying degrees of elevation in all animals exposed to both altitudes. Erythrocyte membranes showed significant elevations in malondialdehyde (MDA) at 6300 m, while elevated protein carbonyls were noticeable at both altitudes in whole cells and membranes. These results suggest a positively associated elevation in protein oxidation with altitude in trained rats. At 5700 m, animals were less stressed, unlike at 6300 m, as seen from the magnitude of elevations in the OS indices and from the responses of the antioxidant enzymes.

Adaptation, Physiological↗

Effects of altitude on element accumulation in alpine moss.

We determined trace metal concentrations in mature living tissues of the moss Hylocomium splendens, at different altitude, in the south-eastern Alps of Italy. We hypothesized that if precipitation does not vary with altitude trace element concentrations in moss tissues will not be affected by altitude. Contrary to our hypothesis, element concentrations did vary with altitude even in the absence of any precipitation pattern related to elevation. In particular, concentrations of anthropogenic pollutants (especially Cd and Pb) peaked at mid altitude (1400-1800 m) where frequency of cloud cover was the highest. We concluded that the trace metal concentrations in alpine mosses can be regarded as a reliable estimate of total atmospheric deposition, i.e., including occult deposition by cloudwater. The latter may account for a significant fraction of the total deposition of anthropogenic trace metals, in close relation to cloud cover frequency.

Air Pollutants↗

Predicting hypoxia in cystic fibrosis patients during exposure to high altitudes.

BACKGROUND: For patients with cystic fibrosis (CF)-related partial respiratory insufficiency and reduced arterial oxygen tension at ground level, the mild hypobaric environment on commercial jet aircraft poses the risk of severe hypoxemia. Thus, physicians should be able to estimate the extent of in-flight hypoxia. OBJECTIVES: To derive tools for estimating the expected drop in arterial oxygen partial pressure (paO(2)) and oxygen saturation (saO(2)) in young adult CF patients with mild to moderate airway obstruction during exposure to the hypobaric conditions aboard commercial aircraft and to test the predictive power of a hypobaric chamber simulation. METHODS: Blood gases of 12 CF patients were measured at ground level, at two altitudes in a hypobaric chamber (2000 and 3000 m) and during two 3.5-h flights at cabin altitudes of 1855 m and 1700 m. The altitude dependence of paO(2) and saO(2) in the chamber and during the flights was calculated and results were used to derive estimation equations for in-flight values. RESULTS: In the chamber, saO(2) decreased by 0.33% per 100 m vertical ascent, and this rate increased significantly at altitudes >2000 m. Predicted saO(2) differed from in-flight value by <5%, and agreement between in-flight saO(2) decrease rate and chamber data was good. paO(2) decreased at a rate of 0.99 mm Hg/100 m in the chamber and by 1.33 mm Hg/100 m during flights. None of the subjects showed any clinical symptoms during the flights and the chamber simulation. CONCLUSION: During our worst-case scenario, i.e. the hypobaric chamber simulation at 3000 m, 90% of patients tolerated paO(2) values below the commonly recommended threshold of 50 mm Hg, probably due to adaptation to chronic hypoxemia and lung function impairment. We propose the following equations for an estimation of the expected extent of in-flight hypoxemia in CF patients with mild to moderate airway obstruction and a flight duration of up to 3.5 h: -paO2[Alt]=paO2[ground] -1.33 x Alt[mm Hg], and -saO2[Alt]=saO2[ground] -0.33 x Alt [%], with Alt=altitude in 100 m. In addition to the overall clinical situation of a patient, these equations will serve as a practical supportive tool for the assessment of the fitness to fly in the primary care setting.

Adult↗

Endothelial activation and cell adhesion molecule concentrations in pregnant women living at high altitude.

OBJECTIVES: Maternal physiology at high altitude could be considered to resemble an intermediate state between preeclampsia and normal pregnancy. The objective of the current study was to determine if cell adhesion molecules, known to be increased in preeclampsia, are increased with chronic maternal and placental hypoxia (due to high-altitude residence) in the absence of preeclampsia. METHODS: Serum was collected from women residing at 3100 m or 1600 m in the three trimesters of pregnancy and postpartum. Vascular cell adhesion molecule-1 (VCAM-1), E-selectin, and intercellular adhesion molecule-1 (ICAM-1) were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: General linear model (GLM) repeated measures analysis of VCAM-1, E-selectin, and ICAM-1 data showed there were no statistically significant effects of gestation within either the high- or moderate-altitude groups or between the different altitudes. CONCLUSION: The increase in cell adhesion molecules reported in preeclampsia is not present in pregnant women at high altitude, suggesting that maternal systemic hypoxia is not responsible for this pathway of endothelial cell activation in preeclampsia.

Adult↗

Changes in BOLD and ADC weighted imaging in acute hypoxia during sea-level and altitude adapted states.

Acute normobaric hypoxia as well as longstanding hypobaric hypoxia induce pronounced physiological changes and may eventually lead to impairment of cerebral function. The aim of the present study is to investigate the effect of hypoxia on the cerebral activation response as well as to explore possible structural changes as measured by diffusion weighted imaging. Eleven healthy sea-level residents were studied after 5 weeks of adaptation to high altitude conditions at Chacaltaya, Bolivia (5260 m). The subjects were studied immediately after return to sea-level in hypoxic and normoxic conditions, and the examinations repeated 6 months later after re-adaptation to sea-level conditions. The BOLD response, measured at 1.5 T, was severely reduced during acute hypoxia both in the altitude and sea-level adapted states (50% reduction during an average S(a)O(2) of 75%). On average, the BOLD response magnitude was 23% lower in altitude than sea-level adaptation in the normoxic condition, but in the hypoxic condition, no significant differences were found. A small but statistically significant decrease in the apparent diffusion coefficient (ADC) was seen in some brain regions during acute hypoxia, whereas ADC was slightly elevated in high altitude as compared to sea-level adaptation. It is concluded that hypoxia significantly diminishes the BOLD response, and the mechanisms underlying this finding are discussed. Furthermore, altitude adaptation may influence both the magnitude of the activation-related response, as well as micro-structural features.

Acclimatization↗

Ventilatory acclimatization in awake guinea pigs raised at high altitude.

To determine if laboratory strains of guinea pigs bred at sea level (SL) are "pre-adapted" to high altitude (HA), we raised litter-matched weanling Hartley guinea pigs for 4 months at SL, intermediate altitude (IA, 1250 m) or HA (3800 m) and exposed them acutely to 100, 21 and 12% inspired O2 at their respective altitude of residence. Control animals raised at SL were also exposed acutely to 10 and 8% inspired O2. In awake spontaneously breathing guinea pigs raised at SL, resting minute ventilation and tidal volume increased significantly when inspired O2 tension fell below about 60 mm Hg. In guinea pigs raised at IA or HA, ventilation was higher at any given inspired O2 tension in direct relationship to the altitude of residence. Resting hematocrit was also higher in animals raised at HA than at SL. We conclude that the pattern of ventilatory acclimatization to HA exposure in Hartley guinea pigs is similar to that in laboratory rats and human lowlanders; therefore laboratory guinea pigs are not pre-adapted and are suitable animals for the study of adaptation to high altitude.

Acclimatization↗

Changes in respiratory control after 5 days at altitude.

These experiments examined changes in the chemoreflex control of breathing and acid-base balance after 5 days at altitude (3480 m) in six healthy males. The partial pressures of carbon dioxide (P(CO2)) at which ventilation increased during isoxic hypoxic and hyperoxic modified rebreathing tests at sea level fell significantly at altitude by mean+/-S.E.M. of 12.8+/-2.51 mmHg and 9.5+/-1.77 mmHg, respectively, but response slopes above threshold were unchanged. Altitude exposure produced a respiratory alkalosis evidenced by a decrease in mean resting end-tidal P(CO2) from 41+/-0.84 mmHg at sea level to 32+/-2.04 mmHg at altitude, but pH did not increase significantly from its sea level value. Blood samples were analyzed to discover acid-base changes, using a modification of the equations for acid-base balance proposed by [Stewart, P.A., 1983. Modern quantitative acid-base chemistry. Can. J. Physiol. Pharmacol. 61, 1444-1461]. While strong ion difference at altitude was not significantly different from its sea level value, albumin concentration was increased significantly from 38.6+/-0.30 g L(-1) to 49.8+/-0.76 g L(-1). We suggest that the respiratory alkalosis was produced by a fall in the chemoreflex threshold and pH was corrected by an elevation in the concentration of weakly dissociated protein anions.

Acclimatization↗

The influence of a mouthpiece and noseclip on breathing pattern at rest is reduced at high altitude.

The effects of the instrumentation by a mouthpiece (MP) and a noseclip (NC) on the ventilatory response to short time hypobaric hypoxia were studied in 10 healthy volunteers at rest. The subjects were exposed to simulated altitude of 500 m, 3000 m, 4000 m and again 500 m, each altitude being applied for 30 min in a hypobaric chamber. Resting minute ventilation (VE), tidal volume (VT) and respiratory frequency (fR) using inductive plethysmography were continuously measured in all subjects in a standardized half lying position. The recordings were carried out at each altitude during the first 10 min without MP and NC, then 10 min with them, and the last 10 min again without them. At 500 m during MP+NC breathing VE and VT were increased, whereas fR was not significantly changed. At 3000 m, the VE increase with MP+NC was no more significant and fR was decreased. These effects of MP+NC on respiration disappeared at 4000 m and reappeared after the descent to 500 m. Furthermore, with and without MP and NC the variability of VE at 4000 m was significantly higher than at 500 m before ascent, and in all altitudes the variability of VT was significantly reduced by the MP+NC. It is concluded that the influence of MP+NC on VE, VT and fR is reduced or even abolished at high altitude, whereas the hypoxia induced increase of VE variability is not affected by the instrumentation.

Acclimatization↗

Effects of hiking at altitude on body composition and insulin sensitivity in recovering drug addicts.

In the current study individuals with a history of drug abuse (users of heroin, cocaine, or amphetamine) displayed a 13-100% increase in body weight (self-reported) and exhibited a trend toward insulin resistance. Therefore, we investigated the effects of long-term altitude hiking on insulin sensitivity in this special population. Nine males recovering from drug addiction (ex-addicts) (age 28.7 +/- 1.3 years) and 17 control subjects (age 29 +/- 1.1 years) voluntarily participated in a 25-day hiking activity (altitude 2200-3800 M). On the 25th day of hiking, oral glucose tolerance test (OGTT), insulin response, lean body mass, fat mass, and waist-to-hip ratio (WHR) were measured in all subjects. After the altitude expedition, insulin levels during the OGTT in ex-addicts were similar to controls, suggesting that insulin sensitivity in this special population was normalized by long-term altitude activity. Along with improvements in insulin sensitivity, a significant reduction in WHR, but small increase in lean body mass, was observed. Twenty-five days of altitude activity significantly reverses hyperinsulinemia in the ex-addicts and this improvement appears to be partially associated with the reduction in central fatness.

Adult↗

High-altitude retinopathy.

PURPOSE: To report a patient with high-altitude retinopathy. METHODS: A 30-year-old man with high-altitude retinopathy was examined and treated. RESULTS: After spending 2 weeks at an altitude of 7,000 meters and then descending to sea level, the patient's visual acuity was RE, 20/20 and LE, 20/50. Intraretinal hemorrhages in both eyes and a scotoma in the left eye were found. Blood cell count was normal, but hematocrit had increased to 53%. The patient was treated with isovolemic hemodilution, pentoxifylline, and aspirin, which reduced hematocrit to 41%. Visual acuity and visual field returned to normal, and intraretinal hemorrhages resolved. CONCLUSIONS: High-altitude hemoconcentration should be treated in patients with high-altitude retinopathy.

Adult↗

Refractive changes at extreme altitude after radial keratotomy.

PURPOSE: We studied the effects of altitude on four corneas that had undergone radial keratotomy and four normal corneas exposed to increasing elevation during a high-altitude excursion. METHODS: We measured visual acuity, cycloplegic refraction, keratometry, and intraocular pressure at sea level and after 24-hour exposure to 12,000 and 17,000 ft. RESULTS: We observed a significant increase in spherical equivalence (hyperopic shift) in radial keratotomy eyes exposed to altitude as compared to controls (P < .0001). The average change in spherical equivalent cycloplegic refraction from sea level to 12,000 ft was 1.03 +/- 0.16 diopters and from sea level to 17,000 ft was 1.94 +/- 0.26 diopters. We also observed a significant decrease in keratometry values at altitude as compared with control corneas (P < .0001). The average change in keratometry from sea level to 12,000 ft was 0.59 +/- 0.19 diopter and from sea level to 17,000 ft was 1.75 +/- 0.27 diopters. CONCLUSIONS: Although the specific origin of these changes is open to question, we hypothesize that hypoxic corneal expansion in the area of the radial keratotomy incisions may lead to central corneal flattening and a hyperopic shift in refractive error. The cornea that has undergone radial keratotomy appears to adjust constantly to changing environmental oxygen concentration, producing a new refractive error over a period of 24 hours or more. Additional study is required to identify with certainty the specific origin of the hyperopic shift at high altitude.

Adult↗

Altitude and the risk of bites from mosquitoes infected with malaria and filariasis among the Mianmin people of Papua New Guinea.

The Mianmin are a mobile population occupying a remote lower montane area at 100-1200 m altitude in the north-western interior of Papua New Guinea (PNG). Major medical problems include malaria and bancroftian filariasis. An entomological survey conducted along an altitudinal transect from 170 to 1000m identified Anopheles koliensis as the predominant malaria vector below 650 m, with A. punctulatus dominating at the higher elevations. Proportions of mosquitoes with malaria circumsporozoite antigens diminished with increasing altitude, as did the proportion of mosquitoes infected with stage 3 larvae of Wuchereria bancrofti. These patterns are consistent with increases in the length of the extrinsic incubation period associated with the lower temperatures found at higher altitudes. Inoculation rates varied less regularly with altitude, owing to local variation in biting rates, but were sufficient even at the higher elevations to maintain a high parasite prevalence in the human population. Results support recent suggestions that the 'population-sink' model of the PNG highland fringes needs additionally to consider local variation due to non-altitude-related ecological factors.

Altitude↗

Effect of acetazolamide on exercise performance and muscle mass at high altitude.

The effect of acetazolamide (Az) on exercise performance and muscle mass in acclimatised subjects at an altitude of 4846 m was assessed in 11 subjects and compared with the effect of placebo on 10 other subjects. Exercise performance at 85% maximum heart rate fell by 37% in the Az group and by 45% in controls (p less than 0.05). Weight loss was greater in the placebo group at high altitude (p less than 0.01) and this correlated with the fall in exercise performance (p less than 0.001). During the expedition anterior quadriceps muscle thickness fell by 12.9% in the control group and 8.5% in the Az group (p less than 0.001), while biceps muscle thickness fell by 8.6% in controls and 2.3% in the Az group (p less than 0.001). Measurements of skin-fold thickness indicated a loss of 18% of total body fat in the placebo group and 5% in the Az group by the end of the expedition (p less than 0.001). Calorie intakes at altitudes above 3000 m were low and similar for the two groups. The Az group had fewer symptoms of acute mountain sickness but differences between the two groups were not statistically significant. Acetazolamide is therefore useful for climbers and trekkers who are acclimatised to high altitudes. It could be most useful at extreme altitudes, where maintenance of exercise performance and muscle mass are important.

Acetazolamide↗

QT interval and final portion of T wave: measurements and dispersion in infants born at high altitude.

BACKGROUND: This research was conducted to determine whether the depolarization and repolarization cardiac process of children born at high altitude differs from that of children born at lower altitudes. METHODS: We studied three groups of 30 healthy newborns in the Venezuelan Andes. Group 3500 m consisted of infants born at 3500 m above sea level; Group 3000 m of infants born at 3000 m above sea level and Group 1600 m of infants born at 1600 m above sea level. Conventional 12-lead electrocardiograms were recorded in the 90 newborns. Corrected QT interval, duration from the peak to the end of the T wave, dispersion of QT interval and of the final portion of T wave and heart rate were computed in each subject. RESULTS: The findings of the present study show that infants born at high altitude (Groups 3500 and 3000 m) had a significantly longer corrected QT interval and a significantly shorter peak-to-end of T wave interval. Neither the heart rate nor the indexes of dispersion of the depolarization-repolarization process revealed abnormal values or significant differences among the groups. CONCLUSIONS: These results suggest that the depolarization and repolarization cardiac process of infants born at high altitude differs from that of children born at lower altitudes.

Altitude↗

Measurement of the energy spectrum of cosmic-ray induced neutrons aboard an ER-2 high-altitude airplane.

Crews working on present-day jet aircraft are a large occupationally exposed group with a relatively high average effective dose from galactic cosmic radiation. Crews of future high-speed commercial aircraft flying at higher altitudes would be even more exposed. To help reduce the significant uncertainties in calculations of such exposures, the atmospheric ionizing radiation (AIR) project, an international collaboration of 15 laboratories, made simultaneous radiation measurements with 14 instruments on five flights of a NASA ER-2 high-altitude aircraft. The primary AIR instrument was a highly sensitive extended-energy multisphere neutron spectrometer with lead and steel shells placed within the moderators of two of its 14 detectors to enhance response at high energies. Detector responses were calculated for neutrons and charged hadrons at energies up to 100 GeV using MCNPX. Neutron spectra were unfolded from the measured count rates using the new MAXED code. We have measured the cosmic-ray neutron spectrum (thermal to >10 GeV), total neutron fluence rate, and neutron effective dose and dose equivalent rates and their dependence on altitude and geomagnetic cutoff. The measured cosmic-ray neutron spectra have almost no thermal neutrons, a large "evaporation" peak near 1 MeV and a second broad peak near 100 MeV which contributes about 69% of the neutron effective dose. At high altitude, geomagnetic latitude has very little effect on the shape of the spectrum, but it is the dominant variable affecting neutron fluence rate, which was eight times higher at the northernmost measurement location than it was at the southernmost. The shape of the spectrum varied only slightly with altitude from 21 km down to 12 km (56-201 g cm-2 atmospheric depth), but was significantly different on the ground. In all cases, ambient dose equivalent was greater than effective dose for cosmic-ray neutrons.

Aerospace Medicine↗

Radiation measurements aboard NASA ER-2 high altitude aircraft with the Liulin-4J portable spectrometer.

The risks to aircrew health posed by prolonged exposure to low levels of ionizing radiation at aircraft altitudes have recently received renewed attention. Civil and military aircraft currently on the drawing board are expected to operate at higher altitudes (>12 km) and fly longer ranges than do existing aircraft, thereby exposing their crews to higher levels of ionizing radiation, for longer periods of time. We are currently carrying out dosimetric measurements of the ionizing radiation environment at approximately 20 km altitude using portable Si detectors aboard NASA's two ER-2 high altitude research aircraft. The instruments, Liulin-4J, have been extensively calibrated at several particle accelerators. With these instruments, we can measure not only absorbed dose, but also variation of the absorbed dose as a function of time. We report radiation dose measurements as function of time, altitude, and latitude for several ER-2 missions.

Aircraft↗

Low altitude dose measurements from APEX, CRRES and DMSP.

Dosimeter data taken on the APEX (1994-1996), CRRES (1990-1991) and DMSP (1984-1987) satellites have been used to study the low altitude (down to 350 km) radiation environment. Of special concern has been the inner edge of the inner radiation belt due to its steep gradient. We have constructed dose models of the inner edge of the belt from all three spacecraft and put them into a personal computer utility, called APEXRAD, that calculates dose for user-selected orbits. The variation of dose for low altitude, circular orbits is given as a function of altitude, inclination and particle type. Dose-depth curves show that shielding greater than approximately 1/4 in Al is largely ineffectual for low altitude orbits. The contribution of outer zone electrons to low altitude dose is shown to be important only for thin shields and to have significant variation with magnetic activity and solar cycle.

Altitude↗

Are sildenafil and theophylline effective in the prevention of high-altitude pulmonary edema?

High-altitude pulmonary edema reflects a potentially life-threatening condition affecting susceptible persons in the second night after ascent to altitudes above 2500 m. Currently, nifedipine is the only pharmacological intervention approved for both, prevention and treatment of high-altitude pulmonary edema. We evaluated the application of the phosphodiesterase-V inhibitor sildenafil combined with the non-selective phosphodiesterase-inhibitor theophylline as preventive agents. In theory, the proposed regimen can impede the two main pathophysiological features of high-altitude pulmonary edema: the deleteriously high pulmonary artery pressure (sildenafil's task) on the one hand, and the activation of an inflammatory cascade (theophylline's task) on the other hand. We suggest that these orally applicable phosphodiesterase inhibitors might be useful in the prevention of high-altitude pulmonary edema.

3',5'-Cyclic-GMP Phosphodiesterases↗