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).     

Peripheral chemoreflex function in hyperoxia following ventilatory acclimatization to altitude.

After a period of ventilatory acclimatization to high altitude (VAH), a degree of hyperventilation persists after relief of the hypoxic stimulus. This is likely, in part, to reflect the altered acid-base status, but it may also arise, in part, from the development during VAH of a component of carotid body (CB) activity that cannot be entirely suppressed by hyperoxia. To test this hypothesis, eight volunteers undergoing a simulated ascent of Mount Everest in a hypobaric chamber were acutely exposed to 30 min of hyperoxia at various stages of acclimatization. For the second 10 min of this exposure, the subjects were given an infusion of the CB inhibitor, dopamine (3 microg. kg(-1). min(-1)). Although there was both a significant rise in ventilation (P < 0.001) and a fall in end-tidal PCO(2) (P < 0.001) with VAH, there was no progressive effect of dopamine infusion on these variables with VAH. These results do not support a role for CB in generating the persistent hyperventilation that remains in hyperoxia after VAH.     

Women at altitude: ventilatory acclimatization at 4,300 m.

Women living at low altitudes or acclimatized to high altitudes have greater effective ventilation in the luteal (L) compared with follicular (F) menstrual cycle phase and compared with men. We hypothesized that ventilatory acclimatization to high altitude would occur more quickly and to a greater degree in 1) women in their L compared with women in their F menstrual cycle phase, and 2) in women compared with men. Studies were conducted on 22 eumenorrheic, unacclimatized, sea-level (SL) residents. Indexes of ventilatory acclimatization [resting ventilatory parameters, hypoxic ventilatory response, hypercapnic ventilatory response (HCVR)] were measured in 14 women in the F phase and in 8 other women in the L phase of their menstrual cycle, both at SL and again during a 12-day residence at 4,300 m. At SL only, ventilatory studies were also completed in both menstrual cycle phases in 12 subjects (i.e., within-subject comparison). In these subjects, SL alveolar ventilation (expressed as end-tidal PCO(2)) was greater in the L vs. F phase. Yet the comparison between L- and F-phase groups found similar levels of resting end-tidal PCO(2), hypoxic ventilatory response parameter A, HCVR slope, and HCVR parameter B, both at SL and 4,300 m. Moreover, these indexes of ventilatory acclimatization were not significantly different from those previously measured in men. Thus female lowlanders rapidly ascending to 4,300 m in either the L or F menstrual cycle phase have similar levels of alveolar ventilation and a time course for ventilatory acclimatization that is nearly identical to that reported in male lowlanders.     

Brain stem NO modulates ventilatory acclimatization to hypoxia in mice.

The objective of our study was to assess the role of neuronal nitric oxide synthase (nNOS) in the ventilatory acclimatization to hypoxia. We measured the ventilation in acclimatized Bl6/CBA mice breathing 21% and 8% oxygen, used a nNOS inhibitor, and assessed the expression of N-methyl-d-aspartate (NMDA) glutamate receptor and nNOS (mRNA and protein). Two groups of Bl6/CBA mice (n = 60) were exposed during 2 wk either to hypoxia [barometric pressure (PB) = 420 mmHg] or normoxia (PB = 760 mmHg). At the end of exposure the medulla was removed to measure the concentration of nitric oxide (NO) metabolites, the expression of NMDA-NR1 receptor, and nNOS by real-time RT-PCR and Western blot. We also measured the ventilatory response [fraction of inspired O(2) (Fi(O(2))) = 0.21 and 0.08] before and after S-methyl-l-thiocitrulline treatment (SMTC, nNOS inhibitor, 10 mg/kg ip). Chronic hypoxia caused an increase in ventilation that was reduced after SMTC treatment mainly through a decrease in tidal volume (Vt) in normoxia and in acute hypoxia. However, the difference observed in the magnitude of acute hypoxic ventilatory response [minute ventilation (Ve) 8% - Ve 21%] in acclimatized mice was not different. Acclimatization to hypoxia induced a rise in NMDA receptor as well as in nNOS and NO production. In conclusion, our study provides evidence that activation of nNOS is involved in the ventilatory acclimatization to hypoxia in mice but not in the hypoxic ventilatory response (HVR) while the increased expression of NMDA receptor expression in the medulla of chronically hypoxic mice plays a role in acute HVR. These results are therefore consistent with central nervous system plasticity, partially involved in ventilatory acclimatization to hypoxia through nNOS.     

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     

Decreased exercise muscle lactate release after high altitude acclimatization

Blood lactate concentration during exercise decreases after acclimatization to high altitude, but it is not clear whether there is decreased lactate release from the exercising muscle or if other mechanisms are involved. We measured iliac venous and femoral arterial lactate concentrations and iliac venous blood flow during cycle exercise before and after acclimatization to 4,300 m. During hypoxia, at a given O2 consumption the venous and arterial lactate concentrations, the venous and arterial concentration differences, and the net lactate release were lower after acclimatization than during acute altitude exposure. While breathing O2-enriched air after acclimatization at a given O2 consumption the venous and arterial lactate concentrations and the venous and arterial concentration differences were significantly lower, and the net lactate release tended to be lower than while breathing ambient air at sea level before acclimatization. We conclude that the lower lactate concentration in venous and arterial blood during exercise after altitude acclimatization reflected less net release of lactate by the exercising muscles, and that this likely resulted from the acclimatization process itself rather than the hypoxia per se.     

Anthropometric changes associated with high altitude acclimatization in females

The anthropometric effects of prolonged high altitude exposure were studied in eight college women who lived on the summit of Pikes Peak (14,100 ft.) for 2.5 months. Acclimatization to altitude was associated with a decrease of skin-fold thickness and a reduction in limb circumference, but little change in body weight. It was concluded that these changes reflected a loss of subcutaneous fat during the period of altitude exposure. Altitude exposure did not produce any alterations in trunk circumference at the umbilicus or buttocks, but it did cause an increase in the inspiratory chest circumference at the axillary level and a reduction in expiratory chest circumference at the subscapular level.     

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.     

Effects of acute exposure to high altitude on ventilatory drive and respiratory pattern

To assess changes in ventilatory regulation in terms of central drive and timing, on exposure to high altitude, and the effects of induced hyperoxia at high altitude, six healthy normal lowland subjects (mean age 19.5 +/- 1.64 yr) were studied at low altitude (518 m) and on the first 4 days at high altitude (3,940 m). The progressive increase in resting expired minute ventilation (VE; control mean 9.94 +/- 1.78 to 14.25 +/- 2.67 l/min on day 3, P less than 0.005) on exposure to high altitude was primarily due to a significant increase in respiratory frequency (f; control mean 15.6 +/- 3.5 breaths/min to 23.8 +/- 6.2 breaths/min on day 3, P less than 0.01) with no significant change in tidal volume (VT). The increase in f was due to significant decreases in both inspiratory (TI) and expiratory (TE) time per breath; the ratio of TI to TE increased significantly (control mean 0.40 +/- 0.08 to 0.57 +/- 0.14, P less than 0.025). Mouth occlusion pressure did not change significantly, nor did the ratio of VE to mouth occlusion pressure. The acute induction of hyperoxia for 10 min at high altitude did not significantly alter VE or the ventilatory pattern. These results indicate that acute exposure to high altitude in normal lowlanders causes an increase in VE primarily by an alteration in central breath timing, with no change in respiratory drive. The acute relief of high altitude hypoxia for 10 min has no effect on the increased VE or ventilatory pattern.     

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)