No abstract

Anecdotal evidence surrounding Tibetans' and Sherpas' exceptional tolerance to hypobaric hypoxia has been recorded since the beginning of high-altitude exploration. These populations have successfully lived and reproduced at high altitude for hundreds of generations with hypoxia as a constant evolutionary pressure. Consequently, they are likely to have undergone natural selection toward a genotype (and phenotype) tending to offer beneficial adaptation to sustained hypoxia. With the advent of translational human hypoxic research, in which genotype/phenotype studies of healthy individuals at high altitude may be of benefit to hypoxemic critically ill patients in a hospital setting, high-altitude natives may provide a valuable and intriguing model. The aim of this review is to provide a comprehensive summary of the scientific literature encompassing Tibetan and Sherpa physiological adaptations to a high-altitude residence. The review demonstrates the extent to which evolutionary pressure has refined the physiology of this high-altitude population. Furthermore, although many physiological differences between highlanders and lowlanders have been found, it also suggests many more potential avenues of investigation.

The morbidly obese are known to have impaired respiratory function. A prospective study of the changes in lung volumes, carbon monoxide transfer, and arterial blood gas tensions was undertaken in 29 morbidly obese patients before and after surgery to induce weight loss. Before surgery the predominant abnormality in respiratory function was a reduction in lung volumes. These increased towards normal predicted values after weight loss, with significant increases in functional residual capacity, residual volume, total lung capacity, and expiratory reserve volume. The increases ranged from 14% for total lung capacity to 54% for expiratory reserve volume. After weight loss had been induced the smokers showed mild hyperinflation and air trapping. Resting arterial blood gas tensions improved, with a rise in arterial oxygen tension from 1063 to 13-02 kPa and a fall in arterial carbon dioxide tension from 5-20 to 4-64 kPa. There was no correlation between weight loss and the changes in blood gas tensions or lung volumes. Loss ofweight in the morbidly obese is thus associated with improved lung function. The effects of smoking on lung function could be detected after weight loss, but were masked before treatment by the opposing effects of obesity on residual volume and functional residual capacity.

Maximal exercise at extreme altitudes was studied during the course of the American Medical Research Expedition to Everest. Measurements were carried out at sea level [inspired O2 partial pressure (PO2) 147 Torr], 6,300 m during air breathing (inspired PO2 64 Torr), 6,300 m during 16% O2 breathing (inspired PO2 49 Torr), and 6,300 m during 14% O2 breathing (inspired PO2 43 Torr). The last PO2 is equivalent to that on the summit of Mt. Everest. All the 6,300 m studies were carried out in a warm well-equipped laboratory on well-acclimatized subjects. Maximal O2 uptake fell dramatically as the inspired PO2 was reduced to very low levels. However, two subjects were able to reach an O2 uptake of 1 l/min at the lowest inspired PO2. Arterial O2 saturations fell markedly and alveolar-arterial PO2 differences increased as the work rate was raised at high altitude, indicating diffusion limitation of O2 transfer. Maximal exercise ventilations exceeded 200 l/min at 6,300 m during air breathing but fell considerably at the lowest values of inspired PO2. Alveolar CO2 partial pressure was reduced to 7-8 Torr in one subject at the lowest inspired PO2, and the same value was obtained from alveolar gas samples taken by him at rest on the summit. The results help to explain how man can reach the highest point on earth while breathing ambient air.

Oxygen intake, ventilation and heart rate were measured in six subjects performing ergometer exercise at various altitudes from sea level to 7,440 m (24,400 ft) (Bar. 300 mm Hg) during a Himalayan expedition lasting 8 months. Oxygen intake for a given work rate was constant and independent of altitude, up to the maximum work rate that could be maintained for 5 min. Maximum oxygen intake declined with increase of altitude, reaching 1.46 liters/min at 7,440 m (24,400 ft) in the best subject. Ventilation (STPD) for a given work rate was independent of altitude in light and moderate exercise but increased at each altitude as maximum oxygen intake was approached. Ventilation values of 140–200 liters (BTPS)/min were observed at altitudes above 4,650 m (15,300 ft). Heart rates at altitude were higher at low and moderate work intensities, but the same as or lower than the corresponding sea-level value for the same work load, as maximum oxygen intake was approached. Breathing oxygen at sea-level pressure at 5,800 m (19,000 ft) reduced ventilation and heart rate for a given work rate, restored work capacity almost to sea-level values and increased maximum heart rate. With the aid of data on blood, lung diffusion, and cardiac output from companion studies, the oxygen transport system was analyzed in three subjects, including a high-altitude Sherpa; and evidence is put forward that lung diffusion, cardiac output, and the high oxygen cost of extreme ventilation all contributed to the limitation of exercise at 5,800 m (19,000 ft). respiration, work and altitude; ventilation, work and altitude; heart rate, work and altitude; O2 transport system at high altitudes; altitude acclimatization Submitted on July 29, 1963