Members of the Caudwell Xtreme Everest expedition, testing human adaptation to hypoxia on the roof of the world, write a diary blog for Nature from 30 March, 2007.
We have now been in Nepal for a month and are beginning to set up one of our laboratories high on Mount Everest. This laboratory is situated at Camp 2 (6,800m) in the Western Cwm and will be home to the investigators of the Caudwell Xtreme Everest project for the following week. But before I set off to great heights, here’s some more explanation of what we’re trying to find out.
As lowland residents travel to high altitude they are exposed to increasing levels of hypoxia. The physiological response to this insult is known as acclimatisation and our current understanding of it consists of a number of processes which together increase systemic oxygen delivery. Changes such as hyperventilation, tachycardia [fast heart rate], increased cardiac output and increased red blood cell mass all ensure that as much oxygen as possible is extracted from the rarefied air and passed on to the metabolising tissues which require it. We have known about this adaptive process for many years and its subtleties are detailed in many well respected texts. But what if this increase in oxygen delivery is not the whole story? Perhaps there is more to the process of acclimatisation than we had previously thought.
Certainly in the world of high altitude medicine and physiology we are aware that some individuals are clearly better performers than others in the hypoxic environment found towards the summits of the world’s highest peaks. But studies so far have been unable to demonstrate a clear physiological advantage in such individuals. In fact their physiology is remarkably normal, showing no signs of being more capable of delivering oxygen than those who fair less well at altitude. So how is it that some individuals perform better than others in the face of similar degrees of oxygen delivery?
It is possible that there are advantageous changes in oxygen utilisation occurring within individuals who perform better in a hypoxic environment. More specifically, at the level of the mitochondria, enzymatic changes could be occurring which allow the cells to produces energy more efficiently under low oxygen conditions.
So how do we intend to explore this hypothesis? We have thought long and hard about our methodology and believe that if differences in oxygen utilisation exist between individuals, our study will detect them.
We have invited a group of two hundred healthy individuals to cycle on a cardiopulmonary exercise testing (CPX) system at sea level. They performed exercise at steady state, sub-anaerobic threshold workloads whilst we measured oxygen consumption and carbon dioxide production on a breath-by-breath basis. From this we can calculate oxygen consumption at each of the selected workloads. In small groups these subjects will then trek to Everest base camp (5,300m), repeating the test a total of four more times at increasing altitudes. By comparing oxygen consumption at each of the altitudes we hope to see changes in oxygen consumption and thus efficiency as they ascend. It would be fair to conclude that any change in oxygen consumption would be due to increasing hypoxia.
What advantage would this cellular hypoxic efficiency have for an individual? In evolutionary terms it is difficult to suggest a reason. High altitude mountaineering is hardly a beneficial characteristic to pass on to the next generation and survival of critical illness is a vastly complex process frequently modified by medical intervention. Suffice to say, genetics is clearly a governing factor in the ability of mitochondria to modify their enzymatic processes in the face of hypoxia. We therefore intend to analyse a number of genetic loci known to be involved in human performance and hypoxic signalling. This will enable us to correlate changes in metabolic efficiency with specific genetic polymorphisms in our subjects.
We shall begin our ascent into the Western Cwm tomorrow and when we return I shall tell you how our high altitude exploits went. After a rest of a week or so we shall return to the mountain, this time aiming for the summit.