The use of organisms that are naturally tolerant to limiting supplies of oxygen to probe nature's molecular and metabolic defense strategies against hypoxia is a tried and tested experimental paradigm in biology. We have found in recent studies that the present day descendent of the lowlanders. In pilot position emission tomography (PET) studies of glucose metabolism in heart and brain in these subjects, we found that biomedical adaptations were utilized in order to maintain each organ in energy balance despite the imposed and chronic hypoxia of their home environments. The heart data demonstrated a significant dependence on glucose for basal energy needs, even following an overnight fast. This provisionally has been interpreted as an adaptation, serving to maximize the amount of useful energy obtainable per unit amount of oxygen. Interestingly, the subjects resolved partially, and in one case entirely, to the normal pattern of substrate preference after only 20 days living at sea level. Brain uptake levels of glucose were at the extreme upper end of the normal range and may indicate at least some non-oxygen dependent metabolism to maintain energy balance. Because control and manipulation of the adaptive response could be of immense practical importance, it is imperative to ascertain if these defense mechanisms are general to the human species. For that reason, we propose to extend our study to include subjects that would be expected both genetically and individually also to be hypoxia-adapted, the Sherpas of Nepal.
