Oxygen-hemoglobin affinity at sea level may predict acute illness at altitude: theory and simulation

Acute mountain sickness carries with it serious health and economic costs. In their pursuit of the mechanisms that produce acute mountain sickness, researchers have overlooked the existence of a possible screening test, a test based on individual variation in cerebral oxygen exchange at sea level. In this paper, I highlight the mathematical link between cerebral oxygen exchange at sea level - this is reflected in the magnitude of the oxygen extraction coefficient - and a change in brain blood flow at altitude; this link has been overlooked. A lower oxygen extraction coefficient at sea level can act - at altitude - to reduce the capacity of the intracranial compartment to accommodate brain swelling, exacerbate increases in cell volume, promote the stimulation of angiogenesis, and further cerebral edema, each of which may contribute to acute mountain sickness. In retrospect, it seems obvious that the initial state of cerebral oxygen exchange will impact the cerebral circulatory response to subsequent hypoxia. This deceptively simple notion offers us an opportunity to identify beforehand those people likely to develop acute mountain sickness when they travel to altitude.