Neuropsychological acclimatization to high altitude

Subjects acclimatized to high altitudes manifest improved manual dexterity as well as trunkal and distal limb co-orbination over un-acclimatized subjects. There is no change in reaction time. Improved attentiveness may contribute to the improved performance, as well as the ability to adapt behaviorally to the numerous physiological consequences of hypoxia. From an ecological and perhaps evolutionary standpoint it matters little whether the adjustment to hypoxia involves intrinsic changes in tissue metabolism (physiological), or results from learning compensatory strategies at altitude (behavioral).     

Bilirubinemia and intravascular hemolysis during acclimatization to high altitude

Bilirubinemia has been reported in man and animals exposed to high altitude, but the cause is not well known. Altered conjugation and delayed excretion of the pigment by the liver has been reported to contribute to the high serum bilirubin levels in man and animals exposed to high altitude, but the rate of development of bilirubinemia, the effects of severe polycythemia, altered erythrocyte fragility and intravascular hemolysis have not been thoroughly investigated. A study was made of the serum bilirubin concentration and the extent of intravascular hemolysis in rats during acclimatization to a simulated altitude of 5,500 m. During both continuous and intermittent (4h/d) exposure the serum bilirubin was significantly elevated at the end of 4 to 6 weeks. The elevations occurred only after severe polycythemia developed (hematocrit 68.5%, Hb 21.6 g/100 ml). An increase in intravascular hemolysis was found after 2 weeks intermittent exposure and after 4 weeks continuous exposure to 5,500 m. No change in erythrocyte fragility to account for increased intravascular hemolysis was found in any of the rats exposed continuously or intermittently to high altitude. No liver pathology was observed in rats exposed to 5,500 m. Bilirubinemia in the rat exposed to high altitude may have been due to the greatly increased erythrocyte number (hematocrit above 68%) and to a proportionate increase in destruction of erythrocytes, to increased intravascular hemolysis associated with the increased blood viscosity and possibly to an inability of the liver to handle increased levels of serum bilirubin.Presented at the Seventh International Biometeorological Congres, 17–23 August 1975, College Park, Maryland, U.S.A.     

Influence of vanadium on acclimatization of humans to high altitude

 The study was conducted on human volunteers as controls as well as after administration of vanadyl sulphate on induction to high altitude (HA) at 3500 m. The plasma vanadium contents were significantly reduced in the control group on abrupt induction to HA on days 3 and 10, indicating redistribution to other organs/tissues under the stressful situation. In the vanadium salt-treated group, plasma vanadium contents were similar to those obtained at sea-level. Administration of vanadyl sulphate did not act as a diuretic. Moreover the vanadium supplemented group drank more water and also excrete less urine than the control group. Received: 1 November 1995 / Accepted: 9 October 1996     

Evolution of pulmonary diffusing capacity in man during high altitude acclimatization]

Pulmonary diffusing capacity (DLCO) has been measured at 3500 m in highlander and lowlander subjects. DLCO is more elevated in highlanders than in lowlanders. In these subjects, a transient increase of DLCO is observed during the first hours of hypoxia which is related to transient changes in pulmonary circulation.     

High altitude acclimatization in plants: Stomatal frequency and anatomical changes in leaves ofArtemisia species

During high altitude acclimatization both the number of stomata and their pore width decreased. The number of open stomata per unit leaf area in the morning and evening hours was higher as compared to that in plants grown at a lower altitude. Thickness of leaves also decreased at high altitudes but the effect on the size of epidermal, mesophyll and spongy parenchymatous cells varied from species to species. Adaptational significance of these changes are discussed. This work was supported through a grant to the second author by Department of Science and Technology (SERC) Govt. of India.     

Changes in structure and function of the human left ventricle after acclimatization to high altitude

To analyse the role of changes in structure and function of the left ventricle in determining cardiac function at rest and during exercise, several two-dimensional and Doppler echocardiographic measurements were performed on 11 healthy subjects immediately before an Himalayan expedition (Nun, 7135 m), during acclimatization (3 weeks) and 14 days after the return. At rest decreases were found in cardiac index (CI) (3.23 l.min-1.m-2, SD 0.4 vs 3.82 l.min-1.m-2, SD 0.58, P less than 0.01), left ventricular mass (55.3 g.m-2, SD 9.4 vs 65.2 g.m-2, SD 13.5, P less than 0.005) and left ventricular end-diastolic volume (LVEDV) (53.9 ml.m-2, SD 6.9 vs 64.8 ml.m-2, SD 9.1, P less than 0.001) after acclimatization; by contrast the coefficient of peak arterial pressure to left ventricular end-systolic volume (PAP/ESV) (7.8, SD 1.6 vs 6.0, SD 1.8, P less than 0.005) and mean wall stress [286 kdyn.cm-2, SD 31 vs 250 kdyn.cm-2, SD 21 (2.86 N.cm-2, SD 0.31 vs 2.50 N.cm-2, SD 0.21), P less than 0.005] increased. After return to sea level, low values of CI and mass persisted despite a return to normal of LVEDV and preload. A reduction of PAP/ESV was also observed. At peak exercise, PAP/ESV (8.7, SD 2.4 vs 12.8, SD 2.0, P less than 0.0025), CI (9.8 l.min-1.m-2, SD 2.5 vs 11.6 l.min-1.m-2, SD 1.6, P less than 0.05) and the ejection fraction (69%, SD 6 vs 76%, SD 4, P less than 0.05) were lower after return to sea level than before departure.(ABSTRACT TRUNCATED AT 250 WORDS)     

Alterations in the serum electrolyte levels of women during high altitude (4,300 m) acclimatization

Eight, University of Missouri (230 m) college women were exposed for a period of 65 days to an elevation of 4,300 m on Pikes Peak. During the first week of altitude exposure marked increases in the serum levels of chloride, phosphate, proteinate and calcium and marked decreases in the serum levels of sodium, potassium, magnesium and estimated bicarbonate were observed. During the remainder of the altitude sojourn chloride, phosphate, potassium and magnesium reverted toward the initial low altitude value. Serum calcium levels, however, remained elevated during this latter period while sodium levels continued to decrease and proteinate levels continued to increase. There was little or no recovery of the estimated bicarbonate decrement as the period of exposure was prolonged. Two weeks after the subjects returned to Missouri some but not all of the electrolytes returned to their initial levels. Those not recovering completely included calcium, chloride, proteinate and estimated bicarbonate.

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Zusammenfassung Bei acht Studentinnen der Universität von Missouri (230 m) wurden 65 Tage in der Station Pikes Peak (4.300 m) die Elektrolyte im Serum untersucht. Während der 1. Höhenwoche wurde ein deutlicher Anstieg des Chlorids, Phosphats, Proteinats und Calciums und ein deutlicher Abfall des Natriums, Kaliums, Magnesiums und berechneten Bikarbonats im Serum gefunden. In den folgenden Wochen kehrten die Werte des Chlorids, Phosphats, Kalium und Magnesium zu den Werten vor dem Übergang in die Höhe zurück. Der Calciumspiegel blieb dauernd erhöht, der Natriumspiegel fiel weiter ab, und der Proteinatspiegel stieg weiter an. Eine Verbesserung des Bikarbonatspiegels fand nicht statt. Zwei Wochen nach Rückkehr von der Höhe waren fast alle Elektrolytwerte wieder normal ausser Calcium Chlorid, Proteinat und Bikarbonat im Serum.

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Resume Huit étudiantes de l'université du Missouri (230 m d'altitude) ont séjourné durant 65 jours à Pikes Peak (4.300 m d'altitude). Durant ce laps de temps, on a analysé régulièrement les électrolytes du sérum sanguin. Durant la première semaine de leur séjour en altitude, on a constaté une nette augmentation des chlorires, des phosphates, des protéinates et du calcium ainsi qu'une diminution marquée du sodium, de la potasse, du magnésium et de la valeur calculée du bicarbonate. Au cours des semaines suivantes, la valeur des chlorures, des phosphates, de la potasse et du magnésium s'est rétablie au niveau précédant la montée en altitude. Le taux de calcium est resté élevé alors que celui du sodium a continué de baisser et celui des protéinates à s'élever. On n'a pas constaté d'amélioration du taux de bicarbonate. Deux semaines après le retour en plaine, presque toutes les valeurs des électrolytes étaient redevenues normales dans le sérum, à l'exception de celles du chlorure de calcium, des proteinates et du bicarbonate.

     

Alterations in cerebral dynamics at high altitude following partial acclimatization in humans: wakefulness and sleep.

We tested the hypothesis that, following exposure to high altitude, cerebrovascular reactivity to CO2 and cerebral autoregulation would be attenuated. Such alterations may predispose to central sleep apnea at high altitude by promoting changes in brain PCO2 and thus breathing stability. We measured middle cerebral artery blood flow velocity (MCAv; transcranial Doppler ultrasound) and arterial blood pressure during wakefulness in conditions of eucapnia (room air), hypocapnia (voluntary hyperventilation), and hypercapnia (isooxic rebeathing), and also during non-rapid eye movement (stage 2) sleep at low altitude (1,400 m) and at high altitude (3,840 m) in five individuals. At each altitude, sleep was studied using full polysomnography, and resting arterial blood gases were obtained. During wakefulness and polysomnographic-monitored sleep, dynamic cerebral autoregulation and steady-state changes in MCAv in relation to changes in blood pressure were evaluated using transfer function analysis. High altitude was associated with an increase in central sleep apnea index (0.2 +/- 0.4 to 20.7 +/- 23.2 per hour) and an increase in mean blood pressure and cerebrovascular resistance during wakefulness and sleep. MCAv was unchanged during wakefulness, whereas there was a greater decrease during sleep at high altitude compared with low altitude (-9.1 +/- 1.7 vs. -4.8 +/- 0.7 cm/s; P < 0.05). At high altitude, compared with low altitude, the cerebrovascular reactivity to CO2 in the hypercapnic range was unchanged (5.5 +/- 0.7 vs. 5.3 +/- 0.7%/mmHg; P = 0.06), while it was lowered in the hypocapnic range (3.1 +/- 0.7 vs. 1.9 +/- 0.6%/mmHg; P < 0.05). Dynamic cerebral autoregulation was further reduced during sleep (P < 0.05 vs. low altitude). Lowered cerebrovascular reactivity to CO2 and reduction in both dynamic cerebral autoregulation and MCAv during sleep at high altitude may be factors in the pathogenesis of breathing instability.     

Physiological changes induced by pre-adaptation to high altitude

To study the physiological effects of pre-adaptation to high altitude, seven subjects were submitted to acclimatization at 4350 m followed by intermittent acclimation in a low barometric pressure chamber (5000 m to 8500 m). The subjects then spent 25 days in the Himalayas. Ventilatory and cardiac responses were studied during a hypobaric poikilocapnic hypoxic test performed both at rest and during exercise (100 W) in normoxia and in hypoxia (barometric pressure: 589 hPa, altitude: 4500 m). Haemoglobin, erythrocytes, reticulocytes, packed cell volume, 2,3-diphosphoglycerate (2,3-DPG) and erythropoietin (EPO) were measured. All variables were studied before pre-adaptation to high altitude (A), after the acclimatization period (B), after the acclimation period (C) and after the expedition (D). The ventilatory and cardiac responses were characterized by an increased tidal volume in hypoxia (+ 33% during exercise in B,P < 0.05; + 100% at rest and + 33% during exercise in C,P < 0.05) without any change in respiratory frequency, whereas an increased systolic blood pressure was only observed in C during exercise in hypoxia [+23 mmHg (3.07 kPa),P<0.01]. Arterial O2 saturation was higher in hypoxia in C and D, both at rest (+8.2% and +4.7%,P<0.01, respectively), and during exercise (+6.3% and +6.3%,P<0.01, respectively). Erythrocytes, haemoglobin and packed cell volume did not vary significantly. The number of reticulocytes was higher in B (+172%,P<0.05) and in C (+249%,P<0.05). EPO and 2,3-DPG increased only in C (+ 770%,P<0.01 and +23%,P<0.05, respectively). These results showed that a combination of continuous pre-acclimatization on Mont Blanc and intermittent acclimation in the hypobaric chamber triggered efficient pre-adaptation mechanisms allowing climbers to save 1 to 2 weeks of acclimatization on the mountain without clinical inconvenience.     

Heme oxygenase activity in fetal and adult sheep is not altered by acclimatization to high altitude hypoxia

Hypoxic stress has been reported to induce the expression of stress proteins such as heme oxygenase (HO), which catalyze the breakdown of heme to generate biliverdin, ferrous iron, and carbon monoxide. These degradation products play a role in the regulation of a variety of processes such as vascular tone, inflammation, and central nervous system function. In mammals, there are 2 catalytically functional HO isozymes, HO-1 (inducible) and HO-2 (constitutive). HO-1 expression is regulated by an array of nonphysiological and physiological stimuli including acute hypoxemia. As relatively little is known of the HO response to prolonged hypoxia in whole animals other than small laboratory rodents, the aim of this work was to examine the effect of long-term hypoxia on total HO activity in fetal and adult ovine tissue. Sheep were maintained at high altitude (3820 m), after which the following tissues were harvested from near-term fetal and non-pregnant ewes for in vitro measurement of HO activity: left ventricle, renal papilla, lung apex, pulmonary artery, carotid artery, mesenteric artery, placental cotyledon, spleen, and brain frontal cortex. There were no significant differences between HO activities in tissues from hypoxic fetal and adult sheep compared with their normoxic controls. Fetal heart HO activities were higher than those of adult tissue (p < 0.05), whereas adult spleen HO activity was significantly higher than that of fetal tissue (p < 0.05). In conclusion, these data indicate that long-term exposure to high altitude hypoxia does not have a persistent effect on HO activity in ovine tissues. Also, except for the spleen where there is a high expression of HO-1 under normal conditions, tissue HO activity is correlated with the expression of HO-2, the constitutive isozyme.     

Autonomic control of the cardiovascular system during acclimatization to high altitude: effects of sildenafil.

Both acute hypoxia and sildenafil may influence autonomic control through transient cardiovascular effects. In a double-blind study, we investigated whether sildenalfil (Sil) could interfere with cardiovascular effects of hypoxia. Twelve healthy men [placebo (Pla) n = 6; Sil, n = 6] were exposed to an altitude of 4,350 m during 6 days. Treatment was continuously administered from 6 to 8 h after arrival at altitude (3 x 40 mg/day). The autonomic control on the heart was assessed by heart rate variability (HRV) during sleep at sea level (SL) and between day 1-2 and day 5-6 in hypoxia. Arterial pressure (AP) and total peripheral resistances (TPR) were obtained during daytime. There was no statistical difference between groups in HRV, AP, and TPR throughout the study. Hypoxia induced a decrease in R-R interval and an increase in AP in both groups. Low frequency-to-high frequency ratio increased at day 1-2 (Pla, P = 0.04; Sil, P = 0.02) and day 5-6 (Pla and Sil, P = 0.04) vs. SL, whereas normalized high-frequency power decreased only in Pla (P = 0.04, day 1-2 vs. SL). Normalized low-frequency power increased at high altitude (Pla and Sil, P = 0.04, day 5-6 vs. SL). TPR decreased at day 2 in Pla (P = 0.02) and tended to normalize at day 6 (P = 0.07, day 6 vs. day 2). Acute hypoxia induced a decrease in parasympathetic and increase in sympathetic tone, which tended to be reversed with acclimatization. Sil had no deleterious effects on the cardiovascular response to high-altitude exposure and its control by the autonomic nervous system.     

Proteomic identification of human serum biomarkers associated with high altitude pulmonary edema

Objective High altitude pulmonary edema （HAPE）, a life-threatening disease, has no biological markers used for the routine prevention, diagnosis and treatment. The aim of this study was to identify serum proteins differentially expressed in patients with HAPE for discovering essential biomarkers. Methods A complete serum proteomic analysis was performed on 10 HAPE patients and on 10 high altitude and 11 sea level healthy people as control using two-dimensional gel electrophoresis, followed by matrix- assisted laser desorption/ionization mass spectrometry and peptide mass fingerprinting. Finally, two most significantly changed proteins were validated by enzyme-linked immunosorbent assay （ELISA）. Results Eight protein spots stained with differential intensity, respresenting 5 distinct proteins were identified in patients compared with healthy controls through analysis of these composite gels. Among them, four proteins, namely alpha 1-antitrypsin（al-AT）, Haptoglobin（Hp）, apolipoprotein A-I （apoA-1） and Complement C3 increased remarkably, while one protein, apolipoprotein A-IV （apoA-IV） decreased significantly. The variation of ~tl-AT and Haptoglobin, as detected by ELISA, was consistent with the results from proteomic analysis. Conclusions It is well known that Hp, al-AT and complement C3 are associated with inflammation and apoA-1 and apoA-IV play important roles in lipid absorption, transport and metabolism. Therefore, the significant expression changes of Hp, al-AT and complement C3 and apoA-1 and apoA-IV between HAPE patients and their corresponding healthy controls highlight the role of inflammatory response system and lipid metabolism system in the pathophysiology of HAPE.