By studying the delivery of oxygen from the air we breathe to its cellular destination in a high altitude environment we may learn more about the physiological adaptations which hypoxic critically ill patients need to develop in order to survive. We believe that the hypobaric hypoxia experienced by lowland residents when they venture to high altitude is an acceptable model for the investigation of possible sea level mechanisms attributable to pathological normobaric hypoxia. Exercise provokes the cardio-respiratory system due to the increased oxygen demand of active skeletal muscles. This stimulus can serve as a tool with which to manipulate cardio-respiratory physiology in the laboratory setting in order to observe the effects of hypoxia at varying levels of oxygen consumption. There remain some important unanswered questions regarding systemic oxygen delivery at high altitude. The possible explanations for a reduced maximal cardiac output during exercise at altitude are numerous and no one hypothesis has yet been proven. Using pulse contour analysis technology and lithium dilution calibration (the LiDCO system, LiDCO Ltd, UK) we will look closely at changes in stroke volume, cardiac output and oxygen delivery during steady state and ramped exercise protocols. The LiDCO system will allow us to plot changes on a beat-by-beat basis throughout the studies. We also hope to return from Everest in the summer of 2007 with the results of the first arterial blood gas to be taken from a climber on the summit (8848m). This may provide some insight into the extraordinary physiological adaptation necessary to perform at such an altitude. We have previously investigated the effect of exercise on gastric perfusion under conditions of normoxia and hypoxia using gastric tonometry to calculate the gastric-end tidal partial pressure of carbon dioxide gap. We have shown that when healthy subjects exercise to maximum exertion in normoxic environment an increase in the gastric-end tidal carbon dioxide gap suggesting a reduction in gastric perfusion (1). Subjects undergoing sub-maximal exercise at an altitude of 5000m also had a reduction in gastric perfusion by the same criterion (2). We are testing the hypothesis that abnormal gastric perfusion occurs at a lower exertional level at high altitude by studying the effects of various peri-anaerobic threshold work rates on gastric perfusion at sea level and high altitude. Even if systemic and regional oxygen delivery is maintained there remains a vital stage of the oxygen cascade which, if defective, will result in inadequate transfer of oxygen to metabolising cells: the microcirculation. This part of the vascular system comprises the arterioles, capillaries and venules; if flow is abnormal in these vessels there may be shunting of oxygenated blood resulting in tissue hypoxia. Using a specialised camera system known as Sidestream Darkfield (SDF) imaging we have been able to study the microcirculation of mucous membranes. In a small pilot study we have demonstrated abnormal blood flow in the sublingual microcirculation at an altitude of 6,400m. Sluggish flow was noted in vessels of small and large calibre. We do not currently know whether this is due to hypoxia or simply due to the raised haematocrit that occurs as a result of acclimatisation to high altitude. We now intend to observe changes in the sublingual microcirculation at greater altitudes, as well as conducting studies to investigate the effect of normalising certain physiological variables on the microcirculation (e.g. barometric pressure in a portable altitude chamber, inspired oxygen partial pressure, haematocrit). By looking at systemic, regional and microcirculatory components of the oxygen delivery process at altitude it is possible that we may answer questions otherwise difficult to address in the critically ill population. We hope to be able to share exciting new data with you when we return from our expedition to Mount Everest this summer.