High Altitude Medicine & Biology

Stroke is a common medical emergency. There is limited knowledge about stroke at high altitude. We present the clinical profile of 30 cases of stroke at high altitude seen at our center between November 1998 to July 2000. A detailed neurological and systemic examination was carried out. Cases were investigated with blood counts, lipid profile, cardiac evaluation, and CT scan/MRI. Coagulation parameters were studied in some cases. Strokes formed 13.7/1000 of hospital admissions from high altitude area, compared to 1.05/1000 in nonhigh altitude area. All our cases from high altitude area were males (serving soldiers of armed forces). Their mean high altitude stay was 10.2 months, and they were all located at heights greater than 4270 m. Age ranged from 22 to 48 years (mean 33.4 yr). Except for smoking (in four cases), they had no preexisting risk factors. Twenty-two cases were of ischemic stroke, 2 of intracerebral hemorrhage, 4 of TIA/RIND (transient ischemic attack/reversible ischemic neurological deficit), and 2 had cerebral venous thrombosis. Out of 30 cases, 28 were of "stroke in young" (<45 yr) and were compared with cases in the same age group from nonhigh altitude areas. Polycythemia with Hb ranging from 16.2 to 22 g·dL^-1 was seen in 21 of these 28 cases (75%). Protein C and S deficiency was found in 1 case in each group. CT scan showed massive infarcts involving at least 50% of one cerebral hemisphere in 12 cases. Multiple infarcts were seen in one case. Conclusion: Long-term stay at high altitude is associated with higher risk of stroke. Although all types of stroke were seen, ischemic stroke was the commonest. Massive infarcts were common. Polycythemia was an important risk factor.

Previous studies suggest that 5 days of prophylactic ginkgo decreases the incidence of acute mountain sickness (AMS) during gradual ascent. This trial was designed to determine if ginkgo is an effective prophylactic agent if begun 1 day prior to rapid ascent. In this double-blind, randomized, placebo-controlled trial, 26 participants residing at sea level received ginkgo (60 mg TID) or placebo starting 24 h before ascending Mauna Kea, Hawaii. Subjects were transported from sea level to the summit (4205 m) over 3 hours, including 1 hour at 2835 m. The Lake Louise Self-report Questionnaire constituted the primary outcome measure at baseline, 2835 m, and after 4 h at 4205 m. AMS was defined as a Lake Louise Self-report Score (LLSR) ≥ 3 with headache. Subjects who developed severe AMS were promptly transported to lower altitude for the remainder of the study. The ginkgo (n = 12) and placebo (n = 14) groups were well matched (58% vs. 50% female; median age 28 yr, range 22-53 vs. 33 yr, range 21-53; 58% vs. 57% Caucasian). Two (17%) subjects on ginkgo and nine (64%) on placebo developed severe AMS and required descent for their safety (p = 0.021); all recovered without sequelae. Median LLSR at 4205 m was significantly lower for ginkgo versus placebo (4, range 1-8 vs. 5, range 2-9, p = 0.03). Ginkgo use did not reach statistical significance for lowering incidence of AMS compared with placebo (ginkgo 7/12, 58.3% vs. placebo 13/14, 92.9%, p = 0.07). Twenty-one of 26 (81%) subjects developed AMS overall. This is the first study to demonstrate that 1 day of pretreatment with ginkgo 60 mg TID may significantly reduce the severity of AMS prior to rapid ascent from sea level to 4205 m.

Myoglobin, a protein with an important role in muscle oxidative metabolism, is increased in high altitude residents. In the closely related hemoglobins, mutations cause or contribute to human disease. Furthermore, heme-containing proteins may be involved in oxygen sensing. We therefore tested the hypotheses that myoglobin allele frequencies differed in Tibetans, a long-resident human high-altitude population, compared with sea-level residents, and varied in relation to altitude among Tibetans. We obtained the sequence of exon 2 of the myoglobin gene in 146 Tibetans with greater than three generations of stable residence at altitude in rural Tibet. We compared the frequency of known polymorphic sites in this gene among Tibetans living at altitudes of 3000, 3700, and 4500 m and to allele frequencies previously obtained in 525 residents of Dallas, Texas. We also examined the association between different myoglobin genotypes and hemoglobin concentration, used as an index of myoglobin levels. The frequency of the myoglobin 79A allele was higher in the high altitude compared with the sea-level residents, but unchanged with increasing altitude among Tibetans. There was no significant deviation from Hardy-Weinberg equilibrium in any of the Tibetan altitude groups, nor was there any association between myoglobin genotype and hemoglobin concentration. Screening of exon 2 of the myoglobin gene in high altitude Tibetans does not show novel polymorphism or selection for specific myoglobin alleles as a function of altitude of residence or hypoxic challenge.

The anorexic effect of exposure to high altitude may be related to the reduction in the arterial oxygen content (Ca_O2) induced by hypoxemia and possibly the associated decreased convective oxygen transport (COT). This study was then performed to evaluate the effects of either transfusion-induced polycythemia or previous acclimation to hypobaria with endogenously induced polycythemia on the anorexic effect of simulated high altitude (SHA) in adult female rats. Food consumption, expressed in g/d/100 g body weight, was reduced by 40% in rats exposed to 506 mbar for 4 d, as compared to control rats maintained in room air. Transfusion polycythemia, which significantly increased hematocrit, hemoglobin concentration, Ca_O2, and COT, did not change the anorexic response to the exposure to hypobaric air. Depression of food intake during exposure to SHA also occurred in rats fasted during 31 h before exposure and allowed to eat ad libitum for 2 h during exposure. Body mass loss was similar in 48-h fasted rats that were either hypoxic or normoxic. Body mass loss was similar in normoxic and hypoxic rats, the former eating the amount of food freely eaten by the latter. Hypoxia-acclimated rats with endogenously induced polycythemia taken to SHA again had diminished food intake and lost body mass at rates that were very close to those found in nonacclimated ones. Exposure to SHA also led to a decrease in food consumption, body weight, and plasma leptin in adult female mice. Analysis of data suggest that body mass loss that accompanies SHA-induced hypoxia is due to hypophagia and that experimental manipulation of the blood oxygen transport capacity cannot ameliorate it. Leptin does not appear to be an inducer of the anorexic response to hypoxia, at least in mice and rats.

Oxygen enrichment of room air has proved to be valuable for people who need to work at altitudes of 4000 m and above. In the present study the feasibility of using the same technique in ski and other mountain resorts at the lower altitudes of 2500 to 4000 m is considered. Although many people find these altitudes invigorating, some are distressed by the hypoxia, especially at night. The analysis shows that all resorts up to an altitude of 3250 m (10,600 ft) can have the equivalent altitude reduced to 1000 m (3280 ft) by oxygen enrichment without incurring a fire hazard. (The equivalent altitude is that which provides the same inspired P_O2 during air breathing.) Even resorts or laboratories as high as 4250 m can have the equivalent altitude safely reduced to 1500 m, that is, lower than the altitude of Denver, Colorado. This application of oxygen enrichment is likely to be most valuable for improving sleep and assisting in the initial acclimatization process.

At extreme altitude, air has an almost identical composition compared to air at sea level, while its pressure is altitude-dependently lower. When supplementary oxygen is used to achieve an acceptable inspiratory pressure of oxygen (PI_O2) during climbing, the barometric pressure difference to lower altitudes is not compensated for. In this report, we tried theoretically to apply pressure support ventilation (PSV) to partially compensate for low barometric pressures. PSV is widely used for respiratory home care and is applicable via a nasal mask. Since there are light-weight units with long battery lives on the market, we speculated that these units may to some extent replace bottled oxygen. PSV was in theory applied at barometric pressures of 400 torr (Everest Base Camp), 284 torr (South Col), and 253 torr (summit of Mt. Everest). We found that during PSV at a mean airway pressure of 16.5 torr on the summit of Mt. Everest, a fraction of inspired oxygen (FI_O2) of 0.34 sufficed to achieve an alveolar partial pressure (PA_O2) of 67 torr. PSV increases PI_O2 by 3.5 torr, which in theory elevates the maximum oxygen consumption (V_O2max) by 218 mL⋅min^-1 in an acclimatized climber in this setting. An additional benefit of PSV at extreme altitude may come from the unloading of the respiratory muscles.

A 35-year-old man on a trek to the Mount Everest region of Nepal presented with a sudden, acute confusional state at an altitude of about 5000 m. Although described at higher altitudes, delirium presenting alone has not been documented at 5000 m or at lower high altitudes. The differential diagnosis which includes acute mountain sickness and high altitude cerebral edema is discussed. Finally, the importance of travelling with a reliable partner and using proper insurance is emphasized in treks to the Himalayas.

Lewis Griffith Cresswell Evans Pugh (1909-1994), best known as the physiologist on the successful 1953 British Everest Expedition, inspired a generation of scientists in the field of altitude medicine and physiology in the decades after World War II. This paper details his early life, his introduction to exercise physiology during the war, and his crucially important work in preparation for the Everest expedition on Cho Oyu in 1952. Pugh's other great contribution to altitude physiology was as scientific leader of the 1960-1961 Himalayan Scientific and Mountaineering Expedition (the Silver Hut), and the origins and results of this important expedition are discussed. He had a major and continuing interest in the physiology of cold, especially in real-life situations in Antarctica, exposure to cold wet conditions on hills in Britain, and in long distance swimming. He also extended his interest to Olympic athletes at moderate altitude (Mexico City) and to heat stress in athletes. Pugh's strength as a physiologist was his readiness to move from laboratory to fieldwork with ease and his rigor in applying the highest standards in both situations. He led by example in both his willingness to act as a subject for experiments and in his attention to detail. He was not an establishment figure; he was critical of authority and well known for his eccentricity, but he inspired great loyalty in those who worked with him.