The equilibration of labeled water (H2 15O)with the exchangeable water pool of brain was examined during a single capillary transit. The labeled water did not equilibrate freely when cerebral blood flow (CBF) exceeded 20 (ml/100 gm)/min in the rhesus monkey. At normal CBF [.. 50 (ml/100 gm)/min] only 90% of the injected bolus freely equilibrated with brain. This value progressively declined as CBF increased.(30: [319][320][321] 1974) Radi oi sotopes of water have been widely assumed to equilibrate with the exchangeable water in brain during a single capillary transit.1-3For this reason, labeled water has been used as a standard for the eval¬ uation of the blood-brain barrier transport and brain distribution of other substances4 and as a tracer for the measurement of cerebral blood flow (CBF).' We present evidence that labeled water does not freely equilibrate with the exchangeable water in brain when mean CBF ex¬ ceeds 20 (ml/100 gm)/min.
MethodsThe fraction of labeled water extracted by the brain during a single capillary tran¬ sit was determined subsequent to the in¬ ternal carotid injection of 0.2 ml of whole blood labeled with H21506 in 20 adult rhesus monkeys. To facilitate the injection of the radioisotope into the internal carotid ar¬ tery, all branches of the right external ca¬ rotid artery were ligated two weeks prior to the experiments. The radioisotope was then injected into the common carotid ar¬ tery through a small (0.021 cm) catheter positioned there under fluoroscopic control from the femoral artery.The monkeys were anesthetized with phencyclidine, paralyzed with gallamine triethiodide, and passively ventilated on 100% oxygen. The end-tidal carbon dioxide pressure (Pco2), arterial blood pressure, and rectal temperature were monitored continuously. Arterial pH, Pco,, and oxy¬ gen pressure were measured before and after each injection.The time course of labeled water through the brain was detected by a 3x2 inch sodium iodide, thallium impregnated scintillation detector appropriately posi¬ tioned and collimated to insure uniform detection efficiency. The signal from the detector, after suitable electronic process¬ ing including narrow pulse height analysis, was processed in a classic small laboratory computer where corrections were made for isotope decay and room background. Tem¬ poral resolution of the data was optimized