Cerebral Blood Flow at High Altitude

This brief review traces the last 50 years of research related to cerebral blood flow (CBF) in humans exposed to high altitude. The increase in CBF within the first 12 hours at high altitude and its return to near sea level values after 3-5 days of acclimatization was first documented with use of the Kety-Schmidt technique in 1964. The degree of change in CBF at high altitude is influenced by many variables, including arterial oxygen and carbon dioxide tensions, oxygen content, cerebral spinal fluid pH, and hematocrit, but can be collectively summarized in terms of the relative strengths of four key integrated reflexes: 1) hypoxic cerebral vasodilatation; 2) hypocapnic cerebral vasoconstriction; 3) hypoxic ventilatory response; and 4) hypercapnic ventilatory response. Understanding the mechanisms underlying these reflexes and their interactions with one another is critical to advance our understanding of global and regional CBF regulation. Whether high altitude populations exhibit cerebrovascular adaptations to chronic levels of hypoxia or if changes in CBF are related to the development of acute mountain sickness are currently unknown; yet overall, the integrated CBF response to high altitude appears to be sufficient to meet the brain's large and consistent demand for oxygen. This short review is organized as follows: An historical overview of the earliest CBF measurements collected at high altitude introduces a summary of reported CBF changes at altitude over the last 50 years in both lowlanders and high-altitude natives. The most tenable candidate mechanism(s) regulating CBF at altitude are summarized with a focus on available data in humans, and a role for these mechanisms in the pathophysiology of AMS is considered. Finally, suggestions for future directions are provided.