High Altitude Medicine & Biology

Migration of aboriginal populations is thought to increase the risk of obesity and associated disorders. In this study, we examined body adiposity, glucose, insulin, leptin, and blood pressure in adult Quechua females living in rural villages in the Cuzco region [n = 105, age 35 ± 10 yr (SD) years] and after migration to Lima from Peruvian Central Andes (n = 105, age 37 ± 10 yr). The two populations are of the same origin and have similar fat composition in their diet, but they differ in degree of physical activity (high in Cuzco, low in Lima) and altitude of living (highland in Cuzco, lowland in Lima). The two groups had similar BMI (24.6 ± 3.9 kg/m² in Cuzco vs. 25.1 ± 4.7 kg/m² in Lima) and waist circumference (83.1 ± 9.8 cm in Cuzco vs. 83.7 ± 10.6 cm in Lima). Yet women in Lima had increased body fat mass (17.7 ± 5.3 kg in Cuzco vs. 21.5 ± 5.8 kg in Lima, p < 0.001) and higher diastolic blood pressure, glucose, insulin, and leptin (all p < 0.001). Also the HOMA assessment of insulin resistance was higher in Lima (p < 0.001). We conclude that migration of Peruvian Amerindian women from the Cuzco region to Lima is associated with increased risk for obesity and cardiovascular diseases without being associated with higher BMI and waist circumference.

The study objective was to determine whether acetazolamide is effective in prophylaxis of acute mountain sickness (AMS) at moderate altitude in ambulatory travelers not undergoing vigorous exercise. Volunteers vacationing in La Paz, Bolivia (3630 m), immediately after arrival from sea level were studied. The design was a double-blind, randomized trial of two doses of acetazolamide (125 mg twice daily, 250 mg twice daily) versus placebo twice daily over a 24-h period. The main outcome measure was AMS score and score trend, using the Lake Louise consensus questionnaire. Nine of 32 subjects (28%) had symptom scoring diagnostic of AMS at 0 h. At 0 and 24 h (respectively), the mean Lake Louise scores were 1.73 and 1.09 for the 11 subjects receiving placebo, 1.45 and 1.36 for the 11 subjects receiving the 125-mg dose, and 2.7 and 0.6 for the 11 subjects receiving the 250-mg dose. The absolute change in these mean scores was not significant for placebo (p = 0.21) or the 125-mg dose (p = 0.88), but was significant for the 250-mg dose (p = 0.008). A comparison of a difference in decline in average AMS score over time showed a statistically significant decline for the 250-mg dosing group versus placebo (p = 0.002). The 250-mg dose of acetazolamide twice daily (but not 125 mg twice daily) was effective in inducing a significant decline in AMS symptoms over the 24-h period after arrival to 3630 m. These results suggest that the dosing of acetazolamide for AMS prevention in nonmountaineering tourists at altitudes below 3700 m should not be lowered below 250 mg twice daily.

This study tested the hypothesis that Andean natives are adapted to high altitude (HA) via high work efficiency during exercise in hypoxia. A total of 186 young males and females were tested in Bolivia, comprising eight different subject groups. Groups were identified based on gender, ancestry (Aymara vs. European), altitude of birth (highlands vs. lowlands), and the altitude where tested (420, 3600, 3850 m). This design allows partitioning of ancestral (i.e., genetic) and developmental effects. To minimize measurement error, subjects were given two submaximal exercise tests on a cycle ergometer (on separate days). Each test consisted of four 5-min work bouts (levels), each separated by a 5-min rest period. For all groups, the oxygen consumption (V_O2)-work rate relationship was not different from the sea-level reference. Gross and net efficiencies (GE and NE) were not different between groups at any work level, with the exception of European men born in the lowlands and acclimatized and tested at 3600 m. These men showed slightly lower V_O2 at high work output, but this may be due to a nonsteady-state V_O2 kinetic, rather than to an altered steady-state V_O2-work rate relationship per se. There were no significant group differences in delta efficiency (DE). In sum, these results provide no support for the hypothesis of energetic advantage during submaximal work in Andean HA natives. A review and analysis of the literature suggest that the same is true for HA natives in the Himalayas.

The generation of reactive oxygen species is typically associated with hyperoxia and ischemia reperfusion. Recent evidence has suggested that increased oxidative stress may occur with hypoxia. We hypothesized that oxidative stress would be increased in subjects exposed to high altitude hypoxia. We studied 28 control subjects living in Lima, Peru (sea level), at baseline and following 48 h exposure to high altitude (4300 m). To assess the effects of chronic altitude exposure, we studied 25 adult males resident in Cerro de Pasco, Peru (altitude 4300 m). We also studied 27 subjects living in Cerro de Pasco who develop excessive erythrocytosis (hematocrit > 65%) and chronic mountain sickness. Acute high altitude exposure led to increased urinary F₂-isoprostane, 8-iso PGF_2α (1.31 ± 0.8 μg/g creatinine versus 2.15 ± 1.1, p = 0.001) and plasma total glutathione (1.29 ± 0.10 μmol versus 1.37 ± 0.09, p = 0.002), with a trend to increased plasma thiobarbituric acid reactive substance (TBARS) (59.7 ± 36 pmol/mg protein versus 63.8 ± 27, p = NS). High altitude residents had significantly elevated levels of urinary 8-iso PGF_2α (1.3 ± 0.8 μg/g creatinine versus 4.1 ± 3.4, p = 0.007), plasma TBARS (59.7 ± 36 pmol/mg protein versus 85 ± 28, p = 0.008), and plasma total glutathione (1.29 ± 0.10 μmol versus 1.55 ± 0.19, p < 0.0001) compared to sea level. High altitude residents with excessive erythrocytosis had higher levels of oxidative stress compared to high altitude residents with normal hematological adaptation. In conclusion, oxidative stress is increased following both acute exposure to high altitude without exercise and with chronic residence at high altitude.

This case report describes three separate episodes of isolated ataxia, hallucinations of being accompanied by another person, and bilateral dressing apraxia occurring in a single individual without prior warning signs. These symptoms are attributable to disruption of vestibular processing in the temporoparietal cortex or associated limbic structures. Neurological dysfunction at high altitude is usually ascribed to high altitude cerebral edema or acute mountain sickness. However, transient neurological symptoms occur abruptly at more extreme altitudes, often following vigorous exertion, without overt altitude-induced prodromes. These symptoms may be caused by intense neuronal discharge or neuronal synchronization as a feature of epileptic discharges or cortical spreading depression. Transient high altitude neurological dysfunction should be recognized as a separate complication of extreme altitude, distinct from high altitude cerebral edema.

In this report, we present the cases of two 63-year-old women who developed high altitude cerebral edema complicated by the occurrence of permanent neuropsychiatric sequelae. They shared a similar clinical course, in that both developed disturbance of consciousness shortly after their arrival at Cuzco, Peru (3500 m), and both developed persistent neuropsychiatric symptoms after resolution of the acute illness. Interestingly, in case 2 there was a 1-month lucid interval between remission of high altitude illness and occurrence of the irreversible neuropsychiatric sequelae. Brain computerized tomography in case 1 and brain magnetic resonance imaging in case 2 disclosed lesions in the globus pallidus bilaterally, suggesting that the neuropsychiatric symptoms in these patients were manifestations of subcortical dementia. The development of high altitude illness was considered to be attributable to mild restrictive lung impairment in case 1 and to a deficient ventilatory response to hypoxia in case 2. It must therefore be borne in mind that irreversible subcortical dementia may be associated with high altitude cerebral edema.