TRACER OXYGEN DISTRIBUTION IS BARRIER-LIMITED IN THE CEREBRAL MICROCIRCULATION

The kinetics of tracer oxygen distribution in the brain microcirculation of the awake dog were investigated with the multiple indicator dilution technique. A bolus containing Cr-51-labeled red blood cells, previously 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 sagittal sinus over the next 30 seconds. The outflow recovery curves were 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 and oxygen rate constants for blood-to-brain exchange and tracer oxygen parenchymal sequestration. Flow to tissue was found to vary between different animals, in concert with parallel changes in oxygen consumption. The O-18(2) outflow curves showed an early peak, coincident with and more than half the magnitude of its vascular reference curve (labeled red blood cells), whereas the [H-3]water curve increased abruptly to a low-in-magnitude curve at low flow values and to a small early peak 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-limited, with the former highly so because of the large red blood cell capacity for oxygen, and that the proportion of the tracer oxygen returning to the circulation from tissue is a small fraction of the total tracer emerging at the outflow.