The kinetics of tracer oxygen distribution in the brain microcirculati
on of the awake dog were investigated with the multiple indicator dilu
tion technique. A bolus containing Cr-51-labeled red blood cells, prev
iously totally desaturated and then resaturated with [O-18](2) (oxygen
), (125)-albumin, Na-22, and [H-3]water, was injected into the carotid
artery, and serial anaerobic blood samples were collected from the sa
gittal sinus over the next 30 seconds. The outflow recovery curves wer
e analyzed with a distributed-in-space two-barrier model for water and
a one-barrier model for oxygen. The analysis provided an estimate of
flow per gram brain weight as well as estimates for the tracer water a
nd oxygen rate constants for blood-to-brain exchange and tracer oxygen
parenchymal sequestration. Flow to tissue was found to vary between d
ifferent animals, in concert with parallel changes in oxygen consumpti
on. The O-18(2) outflow curves showed an early peak, coincident with a
nd more than half the magnitude of its vascular reference curve (label
ed red blood cells), whereas the [H-3]water curve increased abruptly t
o a low-in-magnitude curve at low flow values and to a small early pea
k at high flow values. Analysis indicates that the transfers of both O
-18(2) and [H-3]water indicators from blood to brain are barrier-limit
ed, with the former highly so because of the large red blood cell capa
city for oxygen, and that the proportion of the tracer oxygen returnin
g to the circulation from tissue is a small fraction of the total trac
er emerging at the outflow.