Abstract:The O-labeled water. Over this range of Paco,, a significant linear relationship of CBV = 0.041 Paco, + 2.0 was found. For each one torr change in Paco,, there is a change in CBV of 0.041 ml/100 gm of perfused tissue. At a normocarbic value of Paco, (~37 torr), an average value of 3.5 ml/100 gm was found. A nonlinear relationship of CBV and CBF was found. This relationship is expressed in the equation, CBV = 0.80 CBF 038 . A significant linear relationship was found between CBF and Paco,. This was described by the equation, CBF = 1.8 Paco, -16.75. For each one torr change in the Paco,, there is a 1.8 ml/100 gm per minute change in the CBF. At a normocarbic value of Paco, (~37 torr), an average value of CBF of 50 ml/100 gm per minute was found. The relationship of CBV and t v was nonlinear and was expressed in the equation, t c is o = 41 CBF" 082 . Additional Key Words oxygen-15cerebral metabolic rate of oxygen

Anatomical studies employing the immu- MATERIALS AND METHODS Four adult rhesus monkeys (Macaca mulatta) were used for this study. Four weeks prior to experimentation they were anesthetized with phencyclidine (2 mg/kg) and the right external carotid artery was ligated at its origin to facilitate the injection of '50-labeled water into the internal carotid artery. At the same time, three of the monkeys underwent bilateral superior cervical ganglionectomies. The tissue removed was examined histologically to confirm its identity as sympathetic ganglion.In order to administer drugs that might directly affect the central noradrenergic system, two cannulae systems were stereotaxically implanted 3 weeks prior to experimentation under phencyclidine anesthesia (2 mg/kg). Twenty-three gauge stainless steel permanent guide cannulae were placed in each lateral ventricle in all four animals. These cannulae served to administer drugs intended to affect noradrenergic fibers or terminals. In two of the monkeys (both ganglionectomized) a second set set of guide cannulae was bilaterally implanted in a position directly dorsal to the rostral third of the locus coeruleus. These guide cannulae permitted the placement of 30-gauge injection cannulae at the time of the experiment which extended below the tip of the guide cannulae into the locus coeruleus.At the time of the experiment the monkeys were anesthetized with phencyclidine (2 mg/kg), paralyzed with gallamine, and passively ventilated on 100% oxygen. The end-tidal CO2 pressure (PCo2), arterial blood pressure, and rectal temperature were continuously monitored. Rectal temperature was maintained between 370 and 390 with a heating pad. Arterial pH, and arterial CO2 and 02 pressure (Paco2, and PaO2, respectively) were measured before and after each series of isotope injections.The time course of '50-labeled water through the brain was detected by a 3 X 2 inch sodium iodide, thallium-impregnated scintillation detector appropriately positioned and collimated to insure uniform detection efficiency. The signal from the detector was processed in a manner previously described (4). Radioactive water labeled with l5O (half-life 123 sec) was produced for these studies in the Washington University Medical School Cyclotron by deuteron bombardment of nitrogen gas (5).The extraction fraction of labeled water (E) was obtained by graphically extrapolating the 25-60 sec nearly linear interval of the semilogarithmic plot of tissue water clearance (B, Fig. 1) back to the abscissa of the maximum perfusion peak (A, Fig. 1) and computing the ratio E = B/A.Mean CBF was determined by the height/area residue detection method from the injected bolus of labeled water (4,6). This method requires monitoring of the brain residue 3726

The extraction of 16 O-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 H, 1B O. 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~'), only 90% of the H 2 15

To test the hypothesis that regional cerebral blood flow (rCBF) is normally regulated by regional metabolic activity, rCBF and the regional cerebral metabolic rate for oxygen (rCMRO2) were compared in selected human subjects. In normal subjects and patients with chronic, stable diseases of brain, rCBF correlated well with rCMRO2. In one individual with mild dementia, rCBF and rCMRO2 were measured before and during exercise of the hand and forearm contralateral to the hemisphere studied. Appropriate parallel changes occurred in both rCBF and rCMRO2 during hand exercise. In patients with acute diseases affecting the hemisphere studied, however, the correlation between rCBF and rCMRO2 was unpredictable.

Forty-five studies of regional cerebral blood volume (rCBV), regional cerebral blood flow (rCBF), and regional cerebral oxygen utilization (rCMRO2) were performed in 30 patients undergoing diagnostic cerebral angiography for evaluation of a subarachnoid hemorrhage due to a ruptured intracranial aneurysm. Tracer methods employing radioactive oxygen-15 were used to measure rCBV, rCBF, and rCMRO2. The patient studies were divided into groups based on their neurological status and the presence or absence of cerebral vasospasm. Subarachnoid hemorrhage, with and without vasospasm, produced significant decreases in CBF and CMRO2. In general, patients with more severe neurological deficits, and patients with more severe degrees of vasospasm, had a more marked depression of CBF and CMRO2. The most striking finding was a significant (p less than 0.001) increase in CBV (to 58% above normal) in patients with severe neurological deficits associated with severe cerebral vasospasm. This large increase suggests that cerebral vasospasm consists of constriction of the large, radiographically visible extraparenchymal vessels accompained by a massive dilation of intraparenchymal vessels.