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PubMed1998

Human adaptation to high altitude: regional and life-cycle perspectives.

Studies of the ways in which persons respond to the adaptive challenges of life at high altitude have occupied an important place in anthropology. There are three major regions of the world where high-altitude studies have recently been performed: the Himalayas of Asia, the Andes of South America, and the Rocky Mountains of North America. Of these, the Himalayan region is larger, more geographically remote, and likely to have been occupied by humans for a longer period of time and to have been subject to less admixture or constriction of its gene pool. Recent studies of the physiological responses to hypoxia across the life cycle in these groups reveal several differences in adaptive success. Compared with acclimatized newcomers, lifelong residents of the Andes and/or Himalayas have less intrauterine growth retardation, better neonatal oxygenation, and more complete neonatal cardiopulmonary transition, enlarged lung volumes, decreased alveolar-arterial oxygen diffusion gradients, and higher maximal exercise capacity. In addition, Tibetans demonstrate a more sustained increase in cerebral blood flow during exercise, lower hemoglobin concentration, and less susceptibility to chronic mountain sickness (CMS) than acclimatized newcomers. Compared to Andean or Rocky Mountain high-altitude residents, Tibetans demonstrate less intrauterine growth retardation, greater reliance on redistribution of blood flow than elevated arterial oxygen content to increase uteroplacental oxygen delivery during pregnancy, higher levels of resting ventilation and hypoxic ventilatory responsiveness, less hypoxic pulmonary vasoconstriction, lower hemoglobin concentration, and less susceptibility to CMS. Several of the distinctions demonstrated by Tibetans parallel the differences between natives and newcomers, suggesting that the degree of protection or adaptive benefit relative to newcomers is enhanced for the Tibetans. We thus conclude that Tibetans have several physiological distinctions that confer adaptive benefit consistent with their probable greater generational length of high-altitude residence. Future progress is anticipated in achieving a more integrated view of high-altitude adaptation, incorporating a sophisticated understanding of the ways in which levels of biological organization are articulated and a recognition of the specific genetic variants contributing to differences among high-altitude groups.

Adaptation, Physiological↗

PubMed1999

The pregnant altitude visitor.

The human fetus develops normally under low-oxygen conditions. Exposure of a pregnant woman to the hypoxia of high altitude results in acclimatization responses which act to preserve the fetal oxygen supply. The fetus also utilizes several compensatory mechanisms to survive brief periods of hypoxia. While fetal heart rate monitoring data during air travel suggest no compromise of fetal oxygenation, exercise at high altitude may place further stress on oxygen delivery to the fetus. The limited data on maternal exercise at high altitude suggest good tolerance in most pregnancies; however, short-term abnormalities in fetal heart rate and subsequent pregnancy complications have been observed, as well. A survey of Colorado obstetrical care providers yielded consensus that preterm labor and bleeding complications of pregnancy are the most commonly encountered pregnancy complications among high-altitude pregnant visitors. Dehydration, engaging in strenuous exercise before acclimatization, and participation in activities with high risk of trauma are behaviors that may increase the risk of pregnancy complications. Medical and obstetrical conditions which impair oxygen transfer at any step between the environment and fetal tissue may compromise fetal oxygenation. Knowledge of the medical, obstetrical, and behavioral risk factors during pregnancy at high altitude can help the pregnant visitor to high altitude avoid such complications.

Altitude↗

PubMed1991

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

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

Adrenergic beta-Antagonists↗

PubMed1988

Physiological and metabolic responses to work in heat with graded hypohydration in tropical subjects.

Studies were conducted on 25 healthy male volunteers aged 20-25 years drawn randomly from the tropical regions of India. The subjects initially underwent an 8 day heat acclimatization schedule with 2 hours moderate work in a climatic chamber at 45 degrees C DB and 30% RH. These heat acclimatized subjects were then hypohydrated to varying levels of body weight deficits, i.e. 1.3 +/- 0.03, 2.3 +/- 0.04 and 3.3 +/- 0.04%, by a combination of water restriction and moderate exercise inside the hot chamber. After 2 hours rest in a thermoneutral room (25 +/- 1 degree C) the hypohydrated subjects were tested on a bicycle ergometer at a fixed submaximal work rate (40 W, 40 min) in a hot dry condition (45 degrees C DB, 30% RH, 34 degrees C WBGT). Significant increases in exercise heart rate and oral temperature were observed in hypohydrated subjects as compared to euhydration. Sweat rate increased with 1% and 2% hypohydration as compared to euhydration, but a significant decrease was observed with 3% hypohydration. Na+ & K+ concentrations in arm sweat increased with increase in the level of hypohydration. Oxygen consumption increased significantly only when hypohydration was about 2% or more. It appears that the increased physiological strain observed in tropical subjects working in heat with graded hypohydration is not solely due to reduced sweat rates.

Adult↗

PubMed1983

Chemoreceptor sensitivity and maladaptation to high altitude in man.

Studies were carried out to find out the role of chemoreceptor sensitivity in the causation of maladaptation syndromes on acute exposure to altitude. The experiments were done in two phases. In phase I, the responses in chemoreceptor sensitivity were studied in altitude acclimatized subjects and compared with those who suffered from either High Altitude Pulmonary Oedema (HAPO) or Acute Mountain Sickness (AMS). In Phase II, a similar comparison was done in two groups of subjects, one representing normal sojourners at 3,500 m and the other being subjects who had just recovered from HAPO. The first phase was done at Delhi; and the second at an altitude of 3,500 m. Parameters of assessment were hypoxic sensitivity, carbon dioxide sensitivity, ventilation (VE), respiratory frequency (Rf), forced vital capacity (FVC), forced expiratory volume at the first second (FEV1), heart rate (HR), blood pressure (BP), and oral temperature (Tor). The results showed significantly lower sensitivity to both hypoxia and carbon dioxide in maladapted subjects, as compared to those who were acclimatized in both the categories suggesting thereby that reduced chemoreceptor sensitivity might be an initiating factor in the causation of maladaptation syndromes at altitude.

Adult↗

PubMed1990

On maximal oxygen consumption in hypoxic humans.

The present paper discusses the factors affecting maximal O2 consumption (VO2max) in hypoxia (4300 m above sea level) along the following lines: 1) In acute hypoxia, the fractional limitation to VO2max imposed by circulatory O2 transport (FQ') is 50%, instead of 70% as in normoxia. This is due to the increase in the blood O2 transport coefficient (beta b) as PO2 decreases, as a consequence of the sigmoidal shape of the O2 dissociation curve of hemoglobin. The remaining 50% is assumed to be equally partitioned between tissue O2 transfer (Ft') and mitochondria O2 utilization (Fm'). 2) In chronic hypoxia, FQ' = 0.45, Ft' = 0.20 and Fm' = 0.35, as a consequence of reduced muscle fiber size and muscle mitochondrial density following acclimatization. 3) The relationship between VO2max and PIO2 in both acute and chronic hypoxia reflects the O2 dissociation curve. 4) Acclimatization to chronic hypoxia does not have the function of preserving VO2max.

Acute Disease↗

PubMed1997

Effects of environmental stress on tissue survival and neutrophil recruitment in surgical skin flaps in relation to plasma corticosterone levels in the rat.

OBJECTIVE: Because glucocorticoid treatment can improve the survival of surgical skin flaps, we examined the influence of environmental stress on skin flap survival in the rat. MATERIAL: Female Sprague-Dawley rats. TREATMENT: Dexamethasone (1 mg/kg i.p.). METHODS: A standardized dorsal skin flap was raised and sutured back into position, and six days latter the percentage of flap survival was assessed. Corticosterone in rat plasma was measured using radioimmuno assay, and skin flap myeloperoxidase accumulation (reflecting neutrophil recruitment) was determined spectrophotometrically. RESULTS: Skin flap survival decreased gradually during a 10 day acclimatization period after transportation of the animals from the supplier, and plasma corticosterone levels were increased during the first 5 days of acclimatization compared to day 7 and 10. Dexamethasone treatment of rats accustomed to their new environment for 10 days increased flap survival to a level close to that observed in animals operated at day 1 after arrival. Flap surgery induced pronounced neutrophil recruitment into flap tissue, and this cell accumulation was greatly reduced in both the dexamethasone treated rats and in rats with elevated corticosterone levels. CONCLUSIONS: Skin flap survival in rats exposed to environmental stress may be significantly increased as compared to animals accustomed to their new environment for one week, possibly as a consequence of anti-inflammatory actions exerted by stress-induced elevations in plasma corticosterone. These findings emphasize the importance of strictly controlling environmental stress factors in studies of inflammation and tissue damage after surgical skin trauma.

Animals↗

PubMed1999

Effects of food restriction on food avoidance and risk of acute poisoning of captive feral pigeons from fonofos-treated seeds

Fonofos is a highly toxic insecticide to birds that, when used as a cereal seed treatment, has caused mortality of free-living feral pigeons (Columba livia). Pigeons kept individually under ad libitum feeding conditions in the laboratory do not suffer lethal poisoning because they develop a strong avoidance response to fonofos-treated seed, which restricts consumption to below lethal levels. Two laboratory experiments were conducted to assess the role of avoidance in reducing the risk of acute poisoning of captive birds under food stress. In the first experiment, pigeons acclimatized to feed on untreated wheat seeds for 6 h/day were presented with fonofos-treated seeds for 6 h on a testing day, following normal food surplus in one experimental group (eight birds) and 6 days of deprivation in another (eight birds). In the second experiment, different pigeons were acclimatized to a feeding regime of 2 h/day and treated seeds were offered without previous restriction (eight birds) or after 6 days of food restriction in which birds were given 15% of normal intake (eight birds). In the second experiment, six birds in each experimental group were videotaped to study their feeding behavior. Survivors at the end of the testing day were killed, and all birds were dissected and analyzed to determine carcass and pectoral muscle composition. Food-stressed birds lost approximately 11% of their initial body weight during 6 days of total or partial food restriction, but they still had visible fat deposits and a high body fat content, indicating that they were in good body condition in terms of energy reserves. Consumption of treated seeds on the testing day was reduced in comparison with normal intake of untreated seed in all birds, but there were differences between experimental groups. In ad libitum-fed birds, consumption of treated seed in each experiment averaged 12% and 19% of normal levels, exposure to fonofos was below lethal levels, and no bird died. In food-stressed birds, consumption was higher (34% or 56% of normal levels for the first and second experiments, respectively) and led to the ingestion of seed containing lethal doses of pesticide. Two birds in the first experiment and three in the second died of acute poisoning within around 2 h of initial exposure. The avoidance response developed quickly in both ad libitum-fed and food-stressed birds. Feeding took place in most birds almost exclusively in the first 9 min of the testing day. Within this interval, birds of the two experimental groups stopped ingesting treated seeds around 6 min after the onset of feeding. The differences between experimental groups in consumption of treated seed were due to the higher feeding rate and effective feeding time in food-stressed birds. It is concluded that although feral pigeons under severe food stress develop an early and strong conditioned food aversion to fonofos-treated seeds, avoidance does not always prevent mortality. The need for including hunger stress as a factor in avian dietary toxicity tests to make testing conditions more representative of those experienced by wild birds is discussed. http://link.springer-ny. com/link/service/journals/00244/bibs/37n1p115.html

Journal Article↗

PubMed2003

Horticultural characterization of Angelonia salicariifolia plants transformed with wild-type strains of Agrobacterium rhizogenes.

Genetic transformation was carried out with wild-type strains of Agrobacterium rhizogenes for introducing a dwarf trait into the Scrophulariaceous ornamental plant, angelonia (Angelonia salicariifolia). Leaf segments of two angelonia genotypes (Ang.1 and Ang.2) were co-cultivated with mikimopine-type strains of A. rhizogenes. Adventitious roots that showed vigorous growth and increased lateral branching when cultured on half-strength Murashige and Skoog's (MS) basal salts medium lacking plant growth regulators (PGRs) after co-cultivation were selected as putatively transformed lines. All of these selected lines produced mikimopine. Adventitious shoots were efficiently induced from putatively transformed root segments on half-strength MS basal salts medium containing 1 mg l(-1) benzyladenine (BA) under continuous illumination (24-h photoperiod), and the shoots easily rooted following their transfer to half-strength MS basal salts medium lacking PGRs. The transgenic nature of regenerated plants was confirmed by Southern hybridization. Transformed plants frequently died during their acclimatization, and acclimatized plants of eight transformed lines grew very slowly for 1-5 months after transplantation to the greenhouse. Plants of two transformed lines of Ang.2 flowered 4-6 months after transplantation. These transformed plants exhibited phenotypic alterations such as dwarfness and smaller leaves. There were no apparent alterations observed in the number, shape, and size of the flowers. Pollen fertility of the transformed plants was 60-80% based on aceto-carmine staining. These results indicate the possibility of applying A. rhizogenes-mediated transformation for introducing a dwarf trait into angelonia.

Blotting, Southern↗

PubMed2004

Rapid in vitro adventitious shoot propagation of Scopolia parviflora through rhizome cultures for enhanced production of tropane alkaloids.

A rapid micropropagation system for Scopolia parviflora Nakai (Solanaceae), a rare medicinal plant native to Korea, was established using rhizome cultures. Shoots that originated from adventitious shoots of the rhizome were multiplied when the rhizomes were cultured on half-strength B5 liquid medium supplemented with various growth regulators. Optimum shoot multiplication was observed in half-strength B5 medium containing 3% (w/v) sucrose and 5.77 microM gibberellic acid (GA(3)). Each rhizome gave rise to an average of 12 shoots. Shoot elongation and root induction from multiple shoots occurred on growth regulator-free half-strength B5 solid medium. Healthy plantlets were transferred to a peat moss:vermiculite mixture for acclimatization, which was successful. The concentrations of tropane alkaloids, hyoscyamine and scopolamine were determined in different tissues of native growing plants, in vitro-propagated plants and acclimatized plants by high-performance liquid chromatography. The analysis revealed that the levels of hyoscyamine and scopolamine were higher in in vitro-propagated plants than in the native growing plants. When the rhizome was cut into segments and transferred to optimal culture conditions for multiple shoot propagation, only 12 weeks were required to produce a mature plant. We conclude that in vitro propagation techniques through rhizome cultures provide an efficient and rapid method for shoot propagation of S. parviflora.

Atropine↗

PubMed1995

Seasonal- and temperature-dependent variation in CNS ascorbate and glutathione levels in anoxia-tolerant turtles.

We determined the ascorbic acid (ascorbate) and glutathione (GSH) contents of eight regions of the CNS from anoxia-tolerant turtles collected in summer and in winter. Ascorbate was of special interest because it is found in exceptionally high levels in the turtle CNS. The temperature-dependence of CNS ascorbate content was established by comparing levels in animals collected from two geographic zones with different average winter temperatures and in animals re-acclimated to different temperatures in the laboratory. The analytical method was liquid chromatography with electrochemical detection. Turtle ascorbate levels were 30-40% lower in animals acclimatized to winter (2 degrees C) than to summer (23 degrees C) in all regions of the CNS. Similarly, GSH levels were 20-30% lower in winter than in summer. Winter ascorbate levels were higher in turtles from Louisiana (19 degrees C) than in turtles acclimatized to winter in Wisconsin (2 degrees C). Summer and winter levels of ascorbate could be reversed by re-acclimating animals to cold (1 degree C) or warm (23 degrees C) temperatures for at least one week. CNS water content did not differ between cold- and warm-acclimated turtles. Taken together, the data indicated that ascorbate and GSH undergo significant seasonal variation and that the catalyst for change is environmental temperature. Steady-state ascorbate content showed a linear dependence on temperature, with a slope of 1.5% per degree C that was independent of CNS region. Lower levels of cerebral antioxidants in turtles exposed to colder temperatures were consistent with the decreased rate of cerebral metabolism that accompanies winter hibernation. Cerebral ascorbate and GSH levels in the turtle remained similar to or higher than those in mammals, even during winter, however. These findings support the notion that unique mechanisms of antioxidant regulation in the turtle contribute to their tolerance of the hypoxia-reoxygenation that characterizes diving behavior.

Animals↗

PubMed1986

The thickness of the alveolar capillary wall in the human lung at high and low altitude.

An ultrastructural study of lung biopsy specimens from an adult mestizo highlander from La Paz (3800 m) and three lowlanders from London showed no significant difference in the thickness of the alveolar capillary wall, the thickness in the highlander being 0.65 micron and the range in the lowlanders being 0.57-0.69 micron. The thickness of the blood-air barrier in a mestizo girl of 4 years born and living in La Paz was 0.47 micron. These findings suggest that the alveolar capillary wall in the acclimatized highlander does not differ in thickness from the lowlander. This contrasts with our previous findings in native high altitude guinea pigs which indicate that the alveolar capillary wall is thinner in such indigenous mountain species which are adapted genetically rather than acclimatized to hypobaric hypoxia.

Adult↗

PubMed1985

Ambulatory monitoring of the electroencephalogram in high altitude mountaineers.

Twenty-nine 24 h ambulatory EEG recordings were obtained from 9 British Army mountaineers at heights ranging from 4115 to 6220 m during the period of acclimatization. Three individuals also had ambulatory sea-level EEGs. Sea-level clinical recordings were made on all the mountaineers. All the high altitude EEG recordings were readable and accurate sleep stage scoring was possible on 28 recordings. No paroxysmal activity, which had been reported previously, was noted in any of the high altitude EEGs. There was a marked reduction in stage 4 sleep compared to the amounts normally attained at sea-level, despite strenuous activity which might have been expected to increase slow wave sleep. There was a lesser reduction of REM sleep. These findings are consistent with complaints of poor quality sleep at high altitude, despite ample opportunity for sleep and the maintenance of health. The latter was attributed to careful acclimatization.

Adaptation, Physiological↗

PubMed1987

Endogenous opioids and ventilatory adaptation to prolonged hypoxia in goats.

To investigate whether endogenous opioid peptides mediate time-dependent changes in ventilatory control during prolonged hypoxia, we studied four adult goats at rest during 14 days at simulated high altitude in a hypobaric chamber (PB approximately 450 Torr). Arterial PCO2 fell during the first several hours of hypoxia, remained stable over the next 7 days, and then rose slightly (but without statistical significance) by day 14. Ventilatory responsiveness to CO2 increased during the first week of hypoxia. By day 14, while still greater than control, the ventilatory response to CO2 was less than that observed on day 7. Immunoactive beta-endorphin levels in plasma and CSF did not change during the 14-day period. Administration of naloxone on day 14 did not restore the ventilatory response to CO2 to the level observed during the first week of acclimatization. We conclude that in adult goats, time-dependent changes in ventilatory response to CO2 during acclimatization to prolonged hypoxia are not primarily attributable to alterations in endogenous opioid peptide activity.

Adaptation, Physiological↗

PubMed1994

Sympathetic response during 21 days at high altitude (4,300 m) as determined by urinary and arterial catecholamines.

The sympathoadrenal system plays a major role in adjustments to both short- and long-term high-altitude exposure. Thus, this study investigated catecholamine responses in blood, urine, and muscle during 3 weeks' exposure to 4,300 m in control and beta-blocked subjects. Eleven healthy, sea level (SL)-resident men (aged 26 +/- 1 years) were studied under resting conditions at SL and on arrival and during 21 days at 4,300 m (Pikes Peak). Six subjects received 240 mg/d propranolol, and five were administered a placebo. Compared with SL values (38.7 +/- 4.3 v 32.4 +/- 2.8 micrograms/d for control and beta-blocked, respectively), urinary norepinephrine (NE) excretion increased significantly during altitude exposure, reaching peak values on days 6 to 7 (105.5 +/- 16.1 v 88.4 +/- 12.3 micrograms/d, respectively). Furthermore, resting arterial NE levels (increases 87%), as well as net NE release (decreases 219%) across the leg, both increased during acclimatization, indicating elevated sympathetic activity. Systemic vascular resistance and arterial pressures increased with time at altitude and correlated with NE measurements. Resting heart rates increased initially and then declined steadily after day 4 at altitude in both groups of subjects. Urinary epinephrine (EPI) excretion increased with initial exposure as compared with SL values (5.1 +/- 0.8 to 6.6 +/- 0.7 micrograms/d for control, 4.5 +/- 0.5 to 5.2 +/- 1.3 micrograms/d for beta-blocked); however, no consistent pattern was observed for the following 20 days at altitude. Arterial EPI increased upon acute exposure, but declined after 21 days' acclimatization. No changes in dopamine excretion were observed with beta-blockade or altitude exposure.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗

PubMed1985

The effect of temperature and cell cycle length on SCE frequency in Rat-1 cells.

The effects of temperature on sister-chromatid exchange (SCE) frequency in Rat-1 embryo fibroblasts was investigated by culturing cells at 35 degrees C and 39 degrees C. Cells routinely cultured at 35 degrees C had a significantly lower SCE rate (0.1903 SCE/chromosome) than those routinely cultured at 39 degrees C (2.657 SCE/chromosome). When cells routinely cultured at 35 degrees C were transferred to 39 degrees C, their SCE rate increased to that of the 39 degrees C cells. However, 39 degrees C cells transferred to 35 degrees C did not show a decrease after 24 h acclimatization but after 48 h acclimatization their SCE rate had dropped to that of the 35 degrees C cells. Cells cultured at 35 degrees C had a longer cell cycle time than cells cultured at 39 degrees C, indicating that in Rat-1 cells increased cell cycle time does not result in increased SCE.

Animals↗

PubMed1982

Pinealectomy modifies the thermoregulatory effects of bombesin in goldfish.

Intraventricular administration of the neuropeptide, bombesin, to intact and sham-pinealectomized fish significantly decreased their behaviorally selected internal body temperatures in horizontal thermal gradients. A behavioral hypothermia of 4-7 degrees C was evident regardless of the previous acclimatization temperature (10 or 25 degrees C) and preferred body temperatures selected by individual fish. Pinealectomy increased the body temperatures of all control fish by 2-4 degrees C while markedly reducing the hypothermic effects of administration of bombesin. The hypothermic effects of bombesin were most evident in the pinealectomized fish acclimatized to 10 degrees C. The possible relations between neuropeptides and the pineal gland in the regulation of body temperature are considered.

Animals↗

PubMed1983

The effect of heat on the intestinal and pancreatic levels of amylase and maltase of laying hens and broilers.

The effects of exposing laying hens and broilers daily to intermittent periods of 4 hr heating at 42 degrees C on the intestinal and pancreatic levels of amylase and maltase were investigated. The initial exposure to heat, characterized by heat stress, brought about a significant increase in the duodenum and jejunum parts of the tetra breed hen and only in the duodenum of broilers. The levels of amylase in the distal parts of the intestine of both breeds sharply decreased. The increase in amylase levels in the proximal parts of the intestine under the conditions of initial heating vanished after 3 days of heating; its levels continued to fall in the distal parts. In heat acclimatized laying hens the levels of amylase were lower than those of the control hens both in the intestine and pancreas. The pancreatic level of amylase was reversely related to the levels in the intestine. It is assumed that the intestinal level of amylase is regulated by the pancreas. These findings indicate that the pancreas plays an important role during the adaptation of chickens to heat, through the regulation of intestinal level of amylase. The response in maltase level to heat stress and heat acclimatization was insignificant.

Amylases↗