Evidence of the limitations of water as a freely diffusible tracer in brain of the rhesus monkey

The extraction of ¹⁵O labeled water by the brain during a single capillary transit was studied in vivo in 20 adult rhesus monkeys by external detection of the time course of the tracer subsequent to the internal carotid injection of 0.2 ml of whole blood labeled with H₂¹⁵O. The data showed that labeled water does not freely equilibrate with the exchangeable water in the brain when the mean cerebral blood flow exceeds 30 ml/100 g min-¹. At the normal cerebral blood flow in the rhesus monkey (50 ml/100 g min-¹), only 90% of the H₂¹⁵O is extracted during a single capillary transit. In addition, cerebral blood flow was determined with H₂¹⁵O and ¹³³Xe in these monkeys using residue detection and employing the central volume principle. The data supported the hypothesis that a diffusible tracer, H₂¹⁵O, need not be in complete equilibrium between the phases of a system for the application of the central volume principle to be valid. Finally, the brain capillary permeability surface area product was computed from these data; it was approximately 0.023 cm³/sec g-¹.