Control of ventilation and aerobic work capacity in elite climbers

Hypoxic ventilatory response (HVR), hypercapnic ventilatory response (HCVR), and maximal oxygen uptake (VO2max) were measured in elite male climbers (Clim.: n = 4) and physically active controls (Con.: n = 8). Although mean value of S, an index of HCVR, showed almost the same values in both groups (Clim.: 2.26 +/- 0.62 vs. Con.: 1.85 +/- 0.58 l.min-1.Torr-1), mean value of A, an index of HVR, was significantly higher in climbers than controls (Clim.: 237.8 +/- 109.2 vs. Con.: 111.3 +/- 62.0 l.min-1.Torr-1). Mean value of VO2max in climbers was not different from that in controls (Clim.: 49.3 +/- 2.9 vs. Con.: 47.5 +/- 5.7 ml.kg-1.min-1). These results demonstrate that elite climbers are characterized by their enhanced ventilatory response to hypoxia rather than prominency in aerobic work capacity. It is speculated that enhanced HVR in climbers makes compensation for decreased VO2max at high altitude. The enhanced HVR in elite climbers who have ordinary values in VO2max may be one of factors in their successful performance at extreme altitude.     

Ventilatory chemosensitive adaptations to intermittent hypoxic exposure with endurance training and detraining.

The present study was performed to clarify the effects of intermittent exposure to an altitude of 4,500 m with endurance training and detraining on ventilatory chemosensitivity. Seven subjects (sea-level group) trained at sea level at 70% maximal oxygen uptake (VO2 max) for 30 min/day, 5 days/wk for 2 wk, whereas the other seven subjects (altitude group) trained at the same relative intensity (70% altitude VO2 max) in a hypobaric chamber. VO2 max, hypoxic ventilatory response (HVR), and hypercapnic ventilatory response, as an index of central hypercapnic chemosensitivity (HCVR) and as an index of peripheral chemosensitivity (HCVRSB), were measured. In both groups VO2 max increased significantly after training, and a significant loss of VO2 max occurred during 2 wk of detraining. HVR tended to increase in the altitude group but not significantly, whereas it decreased significantly in the sea-level group after training. HCVR and HCVRSB did not change in each group. After detraining, HVR returned to the pretraining level in both groups. These results suggest that ventilatory chemosensitivity to hypoxia is more variable by endurance training and detraining than that to hypercapnia.     

Blunted hypoxic ventilatory drive in subjects susceptible to high-altitude pulmonary edema

It has been proposed that subjects susceptible to high-altitude pulmonary edema (HAPE) show exaggerated hypoxemia with relative hypoventilation during the early period of high-altitude exposure. Some previous studies suggest the relationship between the blunted hypoxic ventilatory response (HVR) and HAPE. To examine whether all the HAPE-susceptible subjects consistently show blunted HVR at low altitude, we evaluated the conventional pulmonary function test, hypoxic ventilatory response (HVR), and hypercapnic ventilatory response (HCVR) in ten lowlanders who had a previous history of HAPE and compared these results with those of eight control lowlanders who had no history of HAPE. HVR was measured by the progressive isocapnic hypoxic method and was evaluated by the slope relating minute ventilation to arterial O2 saturation (delta VE/delta SaO2). HCVR was measured by the rebreathing method of Read. All measurements were done at Matsumoto, Japan (610 m). All the HAPE-susceptible subjects showed normal values in the pulmonary function test. In HCVR, HAPE-susceptible subjects showed relatively lower S value, but there was no significant difference between the two groups (1.74 +/- 1.16 vs. 2.19 +/- 0.4, P = NS). On the other hand, HAPE-susceptible subjects showed significantly lower HVR than control subjects (-0.42 +/- 0.23 vs. -0.87 +/- 0.29, P less than 0.01). These results suggest that HAPE-susceptible subjects more frequently show low HVR at low altitude. However, values for HVR were within the normal range in 2 of 10 HAPE-susceptible subjects. It would seem therefore that low HVR alone need not be a critical factor for HAPE. This could be one of several contributing factors.     

Effect of hypercapnia and hypoxia on respiratory muscle activation in humans

We studied the electromyographic activity of the diaphragm (EMGdi) and abdominal external oblique (EMGeo) muscles in response to progressive hypercapnia (HCVR) and hypoxia (HVR) in five normal males. The slopes of the regression lines relating log EMGdi activity to minute volume of ventilation (VE) were steeper during HVR runs than HCVR runs (mean +/- SE, 0.03201 +/- 0.00724 vs. 0.02729 +/- 0.00676, P less than 0.03). Phasic expiratory EMGeo activity was seen in 15 of 15 HCVR runs but in only 6 of 15 HVR runs. Furthermore, the maximum level of VE attained before the onset of EMGeo activity was significantly lower during HCVR runs than during HVR runs (23.1 +/- 2.5 vs. 34.8 +/- 4.01/min, P less than 0.003). We conclude that in awake humans 1) the diaphragm is activated to a greater extent by hypoxia than hypercapnia at a given VE and 2) hypercapnia causes a more consistent recruitment of abdominal expiratory activity at lower VE than does hypoxia.     

Relationship between resting ventilatory chemosensitivity and maximal oxygen uptake in moderate hypobaric hypoxia.

This study tested the hypothesis that the extent of the decrement in (.)Vo(2max) and the respiratory response seen during maximal exercise in moderate hypobaric hypoxia (H; simulated 2,500 m) is affected by the hypoxia ventilatory and hypercapnia ventilatory responses (HVR and HCVR, respectively). Twenty men (5 untrained subjects, 7 long distance runners, 8 middle distance runners) performed incremental exhaustive running tests in H and normobaric normoxia (N) condition. During the running test, (.)Vo(2), pulmonary ventilation (Ve) and arterial oxyhemoglobin saturation (Sa(O(2))) were measured, and in two ventilatory response tests performed during N, a rebreathing method was used to evaluate HVR and HCVR. Mean HVR and HCVR were 0.36 +/- 0.04 and 2.11 +/- 0.2 l.min(-1).mmHg(-1), respectively. HVR correlated significantly with the percent decrements in (.)Vo(2max) (%d(.)Vo(2max)), Sa(O(2)) [%dSa(O(2)) = (N-H).N(-1).100], and (.)Ve/(.)Vo(2) seen during H condition. By contrast, HCVR did not correlate with any of the variables tested. The increment in maximal Ve between H and N significantly correlated with %d(.)Vo(2max). Our findings suggest that O(2) chemosensitivity plays a significant role in determining the level of exercise hyperventilation during moderate hypoxia; thus, a higher O(2) chemosensitivity was associated with a smaller drop in (.)Vo(2max) and Sa(O(2)) under those conditions.     

Red cell function at extreme altitude on Mount Everest

As part of the American Medical Research Expedition to Everest in 1981, we measured hemoglobin concentration, red cell 2,3-diphosphoglycerate (2,3-DPG), Po2 at which hemoglobin is 50% saturated (P50), and acid-base status in expedition members at various altitudes. All measurements were made in expedition laboratories and, with the exception of samples from the South Col of Mt. Everest (8,050 m), within 2 h of blood collection. In vivo conditions were estimated from direct measurements of arterial blood gases and pH or inferred from base excess and alveolar PCO2. As expected, increased 2,3-DPG was associated with slightly increased P50, when expressed at pH 7.4. Because of respiratory alkalosis, however, the subjects' in vivo P50 at 6,300 m (27.6 Torr) was slightly less than at sea level (28.1 Torr). The estimated in vivo P50 was progressively lower at 8,050 m (24.9 Torr) and on the summit at 8,848 m (19.4 Torr in one subject). Our data suggest that, at extreme altitude, the blood O2 equilibrium curve shifts progressively leftward because of respiratory alkalosis. This left shift protects arterial O2 saturation at extreme altitude.     

Ventilation and hypoxic ventilatory response of Tibetan and Aymara high altitude natives

Newcomers acclimatizing to high altitude and adult male Tibetan high altitude natives have increased ventilation relative to sea level natives at sea level. However, Andean and Rocky Mountain high altitude natives have an intermediate level of ventilation lower than that of newcomers and Tibetan high altitude natives although generally higher than that of sea level natives at sea level. Because the reason for the relative hypoventilation of some high altitude native populations was unknown, a study was designed to describe ventilation from adolescence through old age in samples of Tibetan and Andean high altitude natives and to estimate the relative genetic and environmental influences. This paper compares resting ventilation and hypoxic ventilatory response (HVR) of 320 Tibetans 9–82 years of age and 542 Bolivian Aymara 13–94 years of age, native residents at 3,800–4,065 m. Tibetan resting ventilation was roughly 1.5 times higher and Tibetan HVR was roughly double that of Aymara. Greater duration of hypoxia (older age) was not an important source of variation in resting ventilation or HVR in either sample. That is, contrary to previous studies, neither sample acquired hypoventilation in the age ranges under study. Within populations, greater severity of hypoxia (lower percent of oxygen saturation of arterial hemoglobin) was associated with slightly higher resting ventilation among Tibetans and lower resting ventilation and HVR among Aymara women, although the associations accounted for just 2–7% of the variation. Between populations, the Tibetan sample was more hypoxic and had higher resting ventilation and HVR. Other systematic environmental contrasts did not appear to elevate Tibetan or depress Aymara ventilation. There was more intrapopulation genetic variation in these traits in the Tibetan than the Aymara sample. Thirty-five percent of the Tibetan, but none of the Aymara, resting ventilation variance was due to genetic differences among individuals. Thirty-one percent of the Tibetan HVR, but just 21% of the Aymara, HVR variance was due to genetic differences among individuals. Thus there is greater potential for evolutionary change in these traits in the Tibetans. Presently, there are two different ventilation phenotypes among high altitude natives as compared with sea level populations at sea level: lifelong sustained high resting ventilation and a moderate HVR among Tibetans in contrast with a slightly elevated resting ventilation and a low HVR among Aymara. Am J Phys Anthropol 104:427–447, 1997. © 1997 Wiley-Liss, Inc.     

Cardiorespiratory response to exercise in men repeatedly exposed to extreme altitude

The ventilatory and heart rate responses to exercise were studied in four experienced high-altitude climbers at sea level and during a 6-wk period above 4,500 m to discover whether their responses to hypoxia were similar to those of high-altitude natives. Comparison was made with results from four scientists who lacked their frequent exposure to extreme altitude. The climbers had greater Vo2max at sea level and altitude but similar ventilatory responses to increasing exercise. On acute hypoxia at sea level their ventilatory response was less than that of scientists. Their heart rate response did not differ from that of scientists at sea level, but with acclimatization the reduction in response was significantly greater. Alveolar gas concentrations were similar after acclimatization, but climbers achieved these changes more rapidly. The increase in hematocrit was similar in the two groups. It is concluded that these climbers, unlike high-altitude residents, have cardiorespiratory responses to exercise similar to those of other lowlanders except that their ventilatory response was lower and the reduction in their heart rate response was greater.     

Evaluation of sympathoadrenal activity, adrenocortical function and androgenic status in five men during a Himalayan mountaineering expedition (ascent of Mt Pabil, 7,102 m, 23,294 ft)

Sympathoadrenal activity, adrenocortical function and androgenic status were studied in five well-trained mountaineers during the different phases of a mountaineering expedition during the ascent of Mt Pabil (7,102 m) in the Ganesh Himal massif. Sympathoadrenal activity was evaluated by measuring urinary excretion of adrenaline, noradrenaline, metanephrines, and vanillinmandelic acid. Adrenocortical function was assessed by measuring urinary excretion of free cortisol, 17 OHCS (17-hydroxycorticosteroids) and androgenic status by measuring testosterone glucuronide, Adiol (5 alpha-androstane-3 alpha, 17 beta diol) and 17KS (17-ketosteroids). Reference values were obtained at Chamonix at 1,037 m during rest. During trekking noradrenaline increased significantly while Adiol and 17-KS decreased. The fall in the urinary androgenic pool persisted during the next phases of the expedition. At base camp (4,800 m) noradrenaline, its metabolites and free cortisol increased mainly during physical activity. Above 6,000 m, adrenaline, noradrenaline, their metabolites, free cortisol and 17-OHCS reached a maximum value. During the return to sea level, the urinary level of these parameters was still high. The drop in the urinary androgenic pool observed during trekking and exposure to high altitude confirms results obtained in other studies on prolonged efforts. This hypoandrogenicity may play an important role in the metabolic adaptations as well as in the mental state of the climbers. The increase of sympathoadrenal activity and of adrenocortical function may be considered as a regulatory element in the adaptative response to hypoxia and other stressors proper to high altitude.     

The effects of intermittent exposure to hypoxia during endurance exercise training on the ventilatory responses to hypoxia and hypercapnia in humans

The present study was performed to investigate the effects of a combination of intermittent exposure to hypoxia during exercise training for short periods on ventilatory responses to hypoxia and hypercapnia (HVR and HCVR respectively) in humans. In a hypobaric chamber at a simulated altitude of 4,500 m (barometric pressure 432 mmHg), seven subjects (training group) performed exercise training for 6 consecutive days (30 min · day⁻¹), while six subjects (control group) were inactive during the same period. The HVR, HCVR and maximal oxygen uptake (V˙O_{2 max}) for each subject were measured at sea level before (pre) and after exposure to intermittent hypoxia. The post exposure test was carried out twice, i.e. on the 1st day and 1 week post exposure. It was found that HVR, as an index of peripheral chemosensitivity to hypoxia, was increased significantly (P < 0.05) in the control group after intermittent exposure to hypoxia. In contrast, there was no significant increase in HVR in the training group after exposure. The HCVR in both groups was not changed by intermittent exposure to hypoxia, while V˙O_{2 max} increased significantly in the training group. These results would suggest that endurance training during intermittent exposure to hypoxia depresses the increment of chemosensitivity to hypoxia, and that intermittent exposure to hypoxia in the presence or absence of exercise training does not induce an increase in the chemosensitivity to hypercapnia in humans. Accepted: 18 March 1998     

Nutritional alterations at high altitude in man

During the French 1980 Mount Pabil (7,102 m) Expedition, a study was made of four altitude-acclimatised climbers (age 36.5 +/- 3.6 years; VO2max 50.5 +/- 3.1 ml X kg-1). Intake of various nutrients, body weight, skinfold thicknesses as indices of body composition, and water and nitrogen balances, were recorded before, and during high altitude exposure, and again after the return to low altitude. There was a significant (35-57%) reduction in total caloric intake at high altitude. Body weight decreased progressively, mainly due to a reduction in body fat. The subjects apparently remained in water balance, while the nitrogen balance was always negative during high altitude exposure. The significant nutritional alterations were mainly observed above 6,000 m. They are discussed with respect to changes in feeding patterns and in hormonal status of the climbers accompanying hypoxia and other stressors proper to high altitude.     

Augmented hypoxic ventilatory response in men at altitude.

To test the hypothesis that the hypoxic ventilatory response (HVR) of an individual is a constant unaffected by acclimatization, isocapnic 5-min step HVR, as delta VI/delta SaO2 (l.min-1.%-1, where VI is inspired ventilation and SaO2 is arterial O2 saturation), was tested in six normal males at sea level (SL), after 1-5 days at 3,810-m altitude (AL1-3), and three times over 1 wk after altitude exposure (PAL1-3). Equal medullary central ventilatory drive was sought at both altitudes by testing HVR after greater than 15 min of hyperoxia to eliminate possible ambient hypoxic ventilatory depression (HVD), choosing for isocapnia a P'CO2 (end tidal) elevated sufficiently to drive hyperoxic VI to 140 ml.kg-1.min-1. Mean P'CO2 was 45.4 +/- 1.7 Torr at SL and 33.3 +/- 1.8 Torr on AL3, compared with the respective resting control end-tidal PCO2 of 42.3 +/- 2.0 and 30.8 +/- 2.6 Torr. SL HVR of 0.91 +/- 0.38 was unchanged on AL1 (30 +/- 18 h) at 1.04 +/- 0.37 but rose (P less than 0.05) to 1.27 +/- 0.57 on AL2 (3.2 +/- 0.8 days) and 1.46 +/- 0.59 on AL3 (4.8 +/- 0.4 days) and remained high on PAL1 at 1.44 +/- 0.54 and PAL2 at 1.37 +/- 0.78 but not on PAL3 (days 4-7). HVR was independent of test SaO2 (range 60-90%). Hyperoxic HCVR (CO2 response) was increased on AL3 and PAL1. Arterial pH at congruent to 65% SaO2 was 7.378 +/- 0.019 at SL, 7.44 +/- 0.018 on AL2, and 7.412 +/- 0.023 on AL3.(ABSTRACT TRUNCATED AT 250 WORDS)     

Respiratory response to chemical stimuli and exercise capacity under conditions of acute hypoxia in elite mountain climbers]

To investigate the factors that modulate exercise performance at extreme altitude, the role of the following variables was analyzed in 16 climbers: 1) ventilatory response to chemical stimuli (hypoxia and hypercapnia); and, 2) maximum exercise performance while breathing room air and during acute hypoxia (F1O2, 0.11). Seven climbers (elite climbers, AE) had previously ascended to 8,000 m or more above sea level, and 9 (A) had never achieved such extreme altitude. Then healthy sedentary subjects (C) of similar age (31.1 +/- 6.0 SD years) were used as control group. Elite climbers showed higher ventilatory responses to both transient hypoxia (-0.49 +/- 0.13 L x min-1 x %-1) (p less than 0.05) and progressive hypoxia (-0.47 +/- 0.13 L x min-1 x %-1) than C (-0.33 +/- 0.14 and -0.30 +/- 0.15 L x min-1 x %-1, respectively). By contrast, no differences were observed between the two groups of climbers. The ventilatory response to hypercapnia was higher in AE (3.04 +/- 1.03 L x min-1 mmHg-1) compared to A (1.85 +/- 0.73 L x min-1 mmHg-1) (p less than 0.05) but similar to that observed in C. Breathing 11% O2, maximum workload and oxyhemoglobin desaturation during maximum exercise were similar in both groups of climbers. Additionally, the ventilatory response to hypoxia did not correlate with maximum workload (F1O2, 0.11), maximal ventilation during exercise (F1O2, 0.11), nor with the altitude score. The present study supports previous reports that inform about the role of the ventilatory response to hypoxia in the exercise performance at high altitude.(ABSTRACT TRUNCATED AT 250 WORDS)     

Muscle structure and performance capacity of Himalayan Sherpas

The ultrastructure of the vastus lateralis muscle of Sherpas from Nepal [5 males; age 28 +/- 2.8 (SD) yr, indirect maximal O2 consumption 48.5 +/- 5.4 ml.kg(-1).min(-1)] was assessed and compared with those of sedentary lowlanders and of Caucasian climbers before and after high-altitude exposure. The mean cross-sectional area of the fibers was 3,186 +/- 521 microns2, i.e., similar to those of Caucasian elite high-altitude climbers (3,108 +/- 303 microns2) and a group of climbers after a 6- to 8-wk sojourn at 5,000-8,600 m (3,360 +/- 580 microns2) but significantly (P less than 0.05) smaller than that of unacclimatized climbers (4,170 +/- 710 microns2) and slightly, although not significantly, lower than that of sedentary lowlanders (3,640 +/- 260 microns2). The number of capillaries per square millimeter of muscle cross section was 467 +/- 22, not significantly smaller than those of climbers on return from a Himalayan expedition (538 +/- 89) and elite high-altitude climbers (542 +/- 127) but significantly (P less than 0.05) greater than that of sedentary lowlanders (387 +/- 25). The volume density of mitochondria was 3.96 +/- 0.54%, significantly (P less than 0.05) less than the values found for any other investigated group, including sedentary subjects at sea level (4.74 +/- 0.30%). It is concluded that Sherpas, like acclimatized Caucasian climbers, are characterized by 1) facilitated convective and diffusive muscle O2 flow conditions and 2) a higher maximal O2 consumption-to-mitochondrial volume ratio than lowlanders despite a reduced mitochondrial volume density.     

Increases in submaximal cycling efficiency mediated by altitude acclimatization.

To investigate the hypothesis that respiratory gas exchange and, in particular, the O(2) consumption (VO(2)) response to exercise is altered after a 21-day expedition to 6,194 m, five male climbers (age 28.2 +/- 2 yr; weight 76.9 +/- 4.3 kg; means +/- SE) performed a progressive and prolonged two-step cycle test both before and 3-4 days after return to sea level. During both exercise tests, a depression (P < 0.05) in VO(2) (l/min) and an increase (P < 0.05) in minute ventilation (VE BTPS; l/min) and respiratory exchange ratio were observed after the expedition. These changes occurred in the absence of changes in CO(2) production (l/min). During steady-state submaximal exercise, net efficiency, calculated from the rates of the mechanical power output to the energy expended (VO(2)) above that measured at rest, increased (P < 0.05) from 25.9 +/- 1.6 to 31. 3 +/- 1.3% at the lighter power output and from 24.4 +/- 1.3 to 29.5 +/- 1.5% at the heavy power output. These changes were accompanied by a 4.5% reduction (P < 0.05) in peak VO(2) (3.99 +/- 0.17 vs. 3.81 +/- 0.18 l/min). After the expedition, an increase (P < 0.05) in hemoglobin concentration (15.0 +/- 0.49 vs. 15.8 +/- 0.41 g/100 ml) was found. It is concluded that, because resting VO(2) was unchanged, net efficiency is enhanced during submaximal exercise after a mountaineering expedition when the exercise is performed soon after return to sea level conditions.     

The simulation effects of mountain climbing training on selected endocrine responses

The simulation effects of mountain climbing exercise training on plasma testosterone, cortisol and luteinizing hormone (LH) levels were examined in ten recreational mountain male climbers. Subjects underwent a simulating mountain climbing exercise training 3 times a week for a total of eight weeks before an expedition to Mount Muztag Ata (7546 m, Xingian, China). During training, each subject carried a 40 kg back pack while walking on a treadmill at a speed of 1.9 mph for 60 min at sea level. Subjects completed an incremental treadmill test to exhaustion prior to training, after training, and one week after returning from Mount Muztag Ata. Blood samples were collected from antecubital vein at rest and at 5, 60, and 120 min post testing to determine the plasma testosterone, cortisol and LH levels. The basal plasma testosterone and cortisol concentrations were lower in both post-training and after-climbing conditions compared with that in the pre-training condition (p<0.01). The basal plasma LH concentration was remained unchanged after training and after the mountain climbing compared with levels measured in the pre-training phase. No correlation could be established between plasma LH and testosterone level. These results suggest that an eight-week period of mountain climbing training protocol may be beneficial in maintaining normal endocrine function during and after high altitude mountain expedition. Our results also indicate the decrease of plasma testosterone was LH independent.     

Ventilatory responses to acute and chronic hypoxia in mice: effects of dopamine D(2) receptors.

We used genetically engineered D(2) receptor-deficient [D(2)-(-/-)] and wild-type [D(2)-(+/+)] mice to test the hypothesis that dopamine D(2) receptors modulate the ventilatory response to acute hypoxia [hypoxic ventilatory response (HVR)] and hypercapnia [hypercapnic ventilatory response (HCVR)] and time-dependent changes in ventilation during chronic hypoxia. HVR was independent of gender in D(2)-(+/+) mice and significantly greater in D(2)-(-/-) than in D(2)-(+/+) female mice. HCVR was significantly greater in female D(2)-(+/+) mice than in male D(2)-(+/+) and was greater in D(2)-(-/-) male mice than in D(2)-(+/+) male mice. Exposure to hypoxia for 2-8 days was studied in male mice only. D(2)-(+/+) mice showed time-dependent increases in "baseline" ventilation (inspired PO(2) = 214 Torr) and hypoxic stimulated ventilation (inspired PO(2) = 70 Torr) after 8 days of acclimatization to hypoxia, but D(2)-(-/-) mice did not. Hence, dopamine D(2) receptors modulate the acute HVR and HCVR in mice in a gender-specific manner and contribute to time-dependent changes in ventilation and the acute HVR during acclimatization to hypoxia.     

Morphological Brain Changes after Climbing to Extreme Altitudes—A Prospective Cohort Study

Background

Findings of cerebral cortical atrophy, white matter lesions and microhemorrhages have been reported in high-altitude climbers. The aim of this study was to evaluate structural cerebral changes in a large cohort of climbers after an ascent to extreme altitudes and to correlate these findings with the severity of hypoxia and neurological signs during the climb.

Methods

Magnetic resonance imaging (MRI) studies were performed in 38 mountaineers before and after participating in a high altitude (7126m) climbing expedition. The imaging studies were assessed for occurrence of new WM hyperintensities and microhemorrhages. Changes of partial volume estimates of cerebrospinal fluid, grey matter, and white matter were evaluated by voxel-based morphometry. Arterial oxygen saturation and acute mountain sickness scores were recorded daily during the climb.

Results

On post-expedition imaging no new white matter hyperintensities were observed. Compared to baseline testing, we observed a significant cerebrospinal fluid fraction increase (0.34% [95% CI 0.10–0.58], p = 0.006) and a white matter fraction reduction (-0.18% [95% CI -0.32–-0.04], p = 0.012), whereas the grey matter fraction remained stable (0.16% [95% CI -0.46–0.13], p = 0.278). Post-expedition imaging revealed new microhemorrhages in 3 of 15 climbers reaching an altitude of over 7000m. Affected climbers had significantly lower oxygen saturation values but not higher acute mountain sickness scores than climbers without microhemorrhages.

Conclusions

A single sojourn to extreme altitudes is not associated with development of focal white matter hyperintensities and grey matter atrophy but leads to a decrease in brain white matter fraction. Microhemorrhages indicative of substantial blood-brain barrier disruption occur in a significant number of climbers attaining extreme altitudes.     

Ancestry explains the blunted ventilatory response to sustained hypoxia and lower exercise ventilation of Quechua altitude natives

Andean high-altitude (HA) natives have a low (blunted) hypoxic ventilatory response (HVR), lower effective alveolar ventilation, and lower ventilation (VE) at rest and during exercise compared with acclimatized newcomers to HA. Despite blunted chemosensitivity and hypoventilation, Andeans maintain comparable arterial O(2) saturation (Sa(O(2))). This study was designed to evaluate the influence of ancestry on these trait differences. At sea level, we measured the HVR in both acute (HVR-A) and sustained (HVR-S) hypoxia in a sample of 32 male Peruvians of mainly Quechua and Spanish origins who were born and raised at sea level. We also measured resting and exercise VE after 10-12 h of exposure to altitude at 4,338 m. Native American ancestry proportion (NAAP) was assessed for each individual using a panel of 80 ancestry-informative molecular markers (AIMs). NAAP was inversely related to HVR-S after 10 min of isocapnic hypoxia (r = -0.36, P = 0.04) but was not associated with HVR-A. In addition, NAAP was inversely related to exercise VE (r = -0.50, P = 0.005) and ventilatory equivalent (VE/Vo(2), r = -0.51, P = 0.004) measured at 4,338 m. Thus Quechua ancestry may partly explain the well-known blunted HVR (10, 35, 36, 57, 62) at least to sustained hypoxia, and the relative exercise hypoventilation at altitude of Andeans compared with European controls. Lower HVR-S and exercise VE could reflect improved gas exchange and/or attenuated chemoreflex sensitivity with increasing NAAP. On the basis of these ancestry associations and on the fact that developmental effects were completely controlled by study design, we suggest both a genetic basis and an evolutionary origin for these traits in Quechua.     

Delayed appearance of high altitude retinal hemorrhages

Background

Retinal hemorrhages have been described as a component of high altitude retinopathy (HAR) in association with altitude illness. In this prospective high altitude study, we aimed to gain new insights into the pathophysiology of HAR and explored whether HAR could be a valid early indicator of altitude illness.

Methodology/Principal Findings

28 mountaineers were randomly assigned to two ascent profiles during a research expedition to Mt. Muztagh Ata (7546 m/24,751 ft). Digital fundus photographs were taken prior to expedition at 490 m (1,607 ft), during expedition at 4497 m (14,750 ft = base camp), 5533 m (18,148 ft), 6265 m (20,549 ft), 6865 m (22,517 ft) and 4.5 months thereafter at 490 m. Number, size and time of occurrence of hemorrhages were recorded. Oxygen saturation (SpO₂) and hematocrit were also assessed. 79% of all climbers exhibited retinal hemorrhages during the expedition. Number and area of retinal bleeding increased moderately to medium altitudes (6265 m). Most retinal hemorrhages were detected after return to base camp from a high altitude. No post-expeditional ophthalmic sequelae were detected. Significant negative (SpO₂ Beta: −0.4, p<0.001) and positive (hematocrit Beta: 0.2, p = 0.002, time at altitude Beta: 0.33, p = 0.003) correlations with hemorrhages were found.

Conclusions/Significance

When closely examined, a very large amount of climbers exhibit retinal hemorrhages during exposure to high altitudes. The incidence of retinal hemorrhages may be greater than previously appreciated as a definite time lag was observed between highest altitude reached and development of retinal bleeding. Retinal hemorrhages should not be considered warning signs of impending severe altitude illness due to their delayed appearance.