Cerebral oxygenation in awake rats during acclimation and deacclimation to hypoxia: an in vivo EPR study. High Alt. Med. Biol. 12:71-77, 2011.-Exposure to high altitude or hypobaric hypoxia results in a series of metabolic, physiologic, and genetic changes that serve to acclimate the brain to hypoxia. Tissue Po 2 (Pto 2 ) is a sensitive index of the balance between oxygen delivery and utilization and can be considered to represent the summation of such factors as cerebral blood flow, capillary density, hematocrit, arterial Po 2 , and metabolic rate. As such, it can be used as a marker of the extent of acclimation. We developed a method using electron paramagnetic resonance (EPR) to measure Pto 2 in unanesthetized subjects with a chronically implanted sensor. EPR was used to measure rat cortical tissue Pto 2 in awake rats during acute hypoxia and over a time course of acclimation and deacclimation to hypobaric hypoxia. This was done to simulate the effects on brain Pto 2 of traveling to altitude for a limited period. Acute reduction of inspired O 2 to 10% caused a decline from 26.7 AE 2.2 to 13.0 AE 1.5 mmHg (mean AE SD). Addition of 10% CO 2 to animals breathing 10% O 2 returned Pto 2 to values measured while breathing 21% O 2, indicating that hypercapnia can reverse the effects of acute hypoxia. Pto 2 in animals acclimated to 10% O 2 was similar to that measured preacclimation when breathing 21% O 2 . Using a novel, individualized statistical model, it was shown that the T 1/2 of the Pto 2 response during exposure to chronic hypoxia was approximately 2 days. This indicates a capacity for rapid adaptation to hypoxia. When subjects were returned to normoxia, there was a transient hyperoxygenation, followed by a return to lower values with a T 1/2 of deacclimation of 1.5 to 3 days. These data indicate that exposure to hypoxia results in significant improvements in steady-state oxygenation for a given inspired O 2 and that both acclimation and deacclimation can occur within days.