Intensivist-led management of brain-dead donors is associated with an increase in organ recovery for transplantation.

The disparity between the number of patients in need of organ transplantation and the number of available organs is steadily rising. We hypothesized that intensivist-led management of brain dead donors would increase the number of organs recovered for transplantation. We retrospectively analyzed data from all consented adult brain dead patients in the year before (n = 35) and after (n = 43) implementation of an intensivist-led donor management program. Donor characteristics before and after implementation were similar. After implementation of the organ donor support team, the overall number of organs recovered for transplantation increased significantly (66 out of 210 potentially available organs vs. 113 out of 258 potentially available organs, p = 0.008). This was largely due to an increase in the number of lungs (8 out of 70 potentially available lungs vs. 21 out of 86 potentially available lungs; p = 0.039) and kidneys (31 out of 70 potentially available kidneys vs. 52 out of 86 potentially available kidneys; p = 0.044) recovered for transplantation. The number of hearts and livers recovered for transplantation did not change significantly. Institution of an intensivist-led organ donor support team may be a new and viable strategy to increase the number of organs available for transplantations.

Abnormalities in fluids, electrolytes, and metabolism of organ donors.

Abnormal serum concentrations of electrolytes, hormones, and glucose are common throughout donor care. The organ procurement coordinator must properly interpret and plan treatment for these changes to prevent intracellular dysfunction in donor organs. This article describes abnormalities in magnesium, phosphorous, calcium, sodium, potassium, and glucose levels; polyuria; and thyroid and pituitary changes. Their potential consequences are discussed, and recommendations for treatment options are presented.

Management of variations in blood pressure during care of organ donors.

The organ procurement coordinator commonly must correct and maintain the arterial blood pressure during donor care. This article reviews considerations in the accurate measurement of the blood pressure, causes of hypertension and hypotension, and desirable standards to use in order to provide adequate organ perfusion. Recommendations are presented for treatment of hypotension in a titrated response of intravenous fluids, inotropic support, and vasopressor infusion to maintain the mean arterial pressure above 65 mm Hg. Collaborative interaction between the coordinator and physician consultant remains important throughout management of blood pressure changes during donor care.

Recommendations for mechanical ventilation during donor care.

The organ procurement coordinator usually directs adjustments to the mechanical ventilator during donor care. It is often difficult to achieve optimal oxygen uptake and carbon dioxide removal while avoiding barotrauma or undesirable effects on the cardiac output. Interrelationships among a variety of ventilator parameters must be understood in order to achieve the desired goal of providing the best organs possible. These recommendations review the key ventilator parameters of tidal volume; positive end-expiratory pressure; auto-positive end-expiratory pressure; fraction of inspired oxygen; and flowrate and frequency and their interactions in controlling peak, plateau, and mean and end-expiratory airway pressures.

Current considerations in the issue of brain death.

Brain death is an anatomically and physiologically complex process. The societal and psychological implications of brain death and organ donation are equally complex, and they have profound ramifications. Because the vast majority of organ donors die as a consequence of catastrophic intracranial processes, neurosurgeons are in a unique position to positively influence the supply of transplantable organs. Enhanced knowledge of the physiology of evolving brain death will improve the care of potential organ donors and increase the probability of successful transplantation. Likewise, better information about patient and family directives, beliefs, grieving, concurrent exposure to other health care workers, and experiences in the hospital environment will assist the neurosurgeon in providing the family with the opportunity for donation. Neurosurgeons can also play a leading role in the multidisciplinary approach required to support the families of potential organ donors during the transition from neurointerventional therapy to somatic support. New federal regulations on organ donation and a review of the literature about the "art of asking" are presented.

A new locus (vsp417-4) belonging to the tsa417-like subfamily of variant-specific surface protein genes in Giardia intestinalis.

A new variant-specific surface protein gene locus (vsp417-4) of Giardia intestinalis is described. Vsp417-4 represents the fourth member of a gene subfamily that is based on a previously described gene, tsa417 ( =vsp417-1). The new locus was detected by characterising DNA amplified in polymerase chain reactions from the 3' ends of divergent homologues (vsp417-4(A-I), vsp417-4(A-II)) found respectively in isolates belonging to the genetic Assemblage A/Group I ('A-I') and Assemblage A/Group II ('A-II') subtypes of G. intestinalis. The complete vsp417-4(A-I) gene was isolated on a 6.2-kb HindIII fragment by screening a genomic DNA library prepared from a type A-I isolate, Ad-1/C7. The deduced polypeptide (VSP417-4(A-I); 709 amino acids, Mr 72662) has properties characterising it as a Giardia variant-specific surface protein, namely a high cysteine content (11.85 mol%), 29 copies of the four amino-acid 'CXXC' motif, and conserved N-terminal signal peptide and C-terminal hydrophobic (membrane-spanning) segments--the latter terminating with the invariant, hydrophilic motif '-CRGKA'. An extended polyadenylation signal sequence (CTTAGRTAGTAAAY), which appears to be a characteristic feature of VSP genes in Giardia, is situated immediately beyond the stop codon. VSP417-4(A-I) shares 87% sequence identity with VSP417-4(A-II) over its C-terminal 235 amino acids, but only 57-58% identity with VSP417-1, VSP417-2 and VSP417-3 which are encoded by other vsp417 family genes identified in these genotypes. Southern hybridisations, using probes derived from the 5' segment of vsp417-4(A-I), indicated the presence of at least five to six closely related loci in both type A-I and type A-II isolates.

Comparison of tsa417-like variant-specific surface protein (VSP) genes in Giardia intestinalis and identification of a novel locus in genetic group II isolates.

A gene (vsp417-3A-II) encoding a new member of the variant-specific surface protein (VSP) family of Giardia is described. Vsp417-3A-II is detected exclusively in isolates belonging to the genetic Assemblage A/Group II sublineage of G. intestinalis, and it is closely related to a previously characterized VSP gene (tsp11, herein renamed vsp417-2A-I) found in Group I isolates of G. intestinalis. Analysis of DNA amplified from the genomes of Group II isolates using consensus primers also revealed products corresponding to the vsp417-2 locus (vsp417-2A-II allele), indicating that vsp417-2A-II and vsp417-3A-II represent separate loci in these organisms. Southern hybridizations revealed a single genomic copy of vsp417-3A-II in Group II isolates, but efforts to detect this locus in Group I organisms were unsuccessful. Together with the vsp417-1 (tsa417) locus that was first identified in the genetic Group I isolate WB and which has been detected since in all tested genetic Group I isolates (as vsp417-1A-I) and in genetic Group II isolates (as vsp417-1A-II), vsp417-3A-II represents a third member of a stable subset of tsa417-like VSP genes in genetic Group II G. intestinalis. The encoded polypeptide, VSP417-3A-II (667 residues, predicted M(r) 69120) possesses a high cysteine content (12.1 mol%), 28 copies of the metal-binding -CXXC- motif, and a highly conserved C-terminal hydrophobic domain--similar to all other characterized Giardia VSP. A revised nomenclature for Giardia VSP genes is proposed, prompted by the need to describe the homologues found in the various major genotypes of the species complex, G. intestinalis.

Giardia intestinalis: conservation of the variant-specific surface protein VSP417-1 (TSA417) and identification of a divergent homologue encoded at a duplicated locus in genetic group II isolates.

The stability of the gene encoding TSA417, a 72-kDa variant-specific surface protein (VSP) produced by trophozoites of Giardia intestinalis isolate WB-C6, was investigated in isolates of similar (Assemblage A / Group I) or distinct (Assemblage A / Group II) genotype. Using primers specific for the WB-C6 tsa417 gene, DNA amplified in polymerase chain reactions from genomic DNA indicated the presence, in every isolate, of an intact coding sequence possessing conserved restriction sites diagnostic for this locus (herein designated vsp417-1). Sequence analysis of the DNA amplified from the genomes of genetic Group I ("A-I") isolates revealed complete identity with the published WB-C6 tsa417 (vsp417-1(A-I)) sequence. Equivalent products, amplified from the genomes of genetic Group II ("A-II") isolates, similarly yielded an invariant and apparently allelic 2142-bp coding sequence (designated vsp417-1(A-II)) possessing 79% nucleotide identity with vsp417-1(A-I) and polymorphisms unique to Group II organisms. The encoded polypeptides (VSP417-1(A-I) and VSP417-1(A-II)) are identical at 75% of amino acid positions. Substitutions are concentrated within the N-terminal portions of the proteins, but the overall structure of VSP417-1 has changed little during the evolution of the Group I and Group II genotypes from their common clonal ancestor. An additional 0.7-kb DNA, representing a separate locus (vsp417-5) encoding a 22.3-kDa VSP, was amplified from genetic Group II genomes exclusively but only using particular primer combinations. The vsp417-5(A-II) gene exhibits >85% sequence identity with the 5' and 3' segments of vsp417-1(A-I) and vsp417-1(A-II) but it lacks a 1482-bp segment that comprises the central portion of the vsp417-1 locus. Excision of this segment seems to have occurred by intragenic recombination, possibly initiated by a stem loop formed between palindromic sequences which border the 1482-bp segment within vsp417-1 but which are contiguous in vsp417-5(A-II). The detection by Southern hybridization of additional genomic sequences that share homology with these genes reveals the existence in these two genotypes of a distinctive "vsp417" gene subset.

Utilization and diagnostic yield of blood cultures in a surgical intensive care unit.

OBJECTIVE: To evaluate the diagnostic yield of blood cultures obtained in a surgical intensive care unit (ICU) and to assess factors potentially influencing yield. DESIGN: Retrospective, descriptive study. SETTING: Surgical ICU in a university hospital. SUBJECTS: All patients who had a blood culture obtained during their admission to the trauma/neurosurgical ICU of Presbyterian University Hospital from January 1, 1993 to December 31, 1993. MEASUREMENTS AND MAIN RESULTS: Blood culture isolates were categorized as pathogens or contaminants and overall diagnostic yield was determined. Blood cultures were positive for pathogens in 4.6% of all culture episodes, while contaminants were isolated in 5.5% of all culture episodes. A total of 23 true bacteremias were identified in 21 patients, for an overall rate of bacteremia of 3.6 per 100 admissions (5.9 per 1,000 patient days). Concurrent antibiotics were being used at the time of blood culture in 65.3% of all culture episodes. The yield for pathogens was significantly lower (2.2%) when cultures were obtained on antibiotics compared with culture episodes obtained off antibiotics (6.4%) (p < .05). Single-set blood culture episodes were obtained in approximately 32% of all culturing episodes with the overall yield for pathogens of these culturing episodes lower (2.9%) than that of multiple-set culture episodes (5.3%) (p = NS). CONCLUSIONS: Blood culture yield in this surgical ICU was relatively low in comparison with other published studies. The data further suggest that concurrent use of systemic antibiotics and inappropriate or excessive culturing may negatively influence blood culture yield.

Compartmentation of whole brain blood flow and oxygen and glucose metabolism in monkeys.

The cerebral metabolic rate of oxygen (CMRO2) has been functionally compartmentalized using the barbiturate thiopental into active CMRO2, associated with electroencephalographic (EEG) activity, and the balance, basal CMRO2, associated with the maintenance of neuronal viability. Previous measurements of these CMRO2 compartments were made in anesthetized animals. Our aim was to determine whether the same proportions for these compartments applied in unanesthetized monkeys. The active: basal distribution of the cerebral metabolic rate of glucose (CMRG) and cerebral flood flow (CBF) were also determined. Three measurements of whole-brain CBF (H2 clearance), CMRO2, and CMRG were made in six unanesthetized rhesus monkeys (Macaca mulatta). Thereafter, thiopental anesthesia was induced and maintained until an isoelectric EEG was obtained. Three additional measurements of CBF, CMRO2, and CMRG were made. Arterial blood pressure, end-tidal CO2, and arterial blood gas were measured with each set of measurements. Thiopental-induced isoelectric EEG resulted in a 47% reduction in CMRO2 from 5.95 +/- 0.54 to 3.10 +/- 0.51 ml/100 g/min (mean +/- SD); a 36% reduction in CBF from 76 +/- 21 to 48 +/- 14 ml/100 g/min; and a 61% reduction in CMRG from 8.09 +/- 2.78 to 3.13 +/- 0.77 mg/100 g/min. The oxygen-glucose index was 0.99 +/- 0.10 for the whole brain, 0.87 +/- 0.15 for the active, and 1.27 +/- 0.25 for the basal compartments. These results indicated an active:basal distribution of approximately 50:50 for CMRO2, 40:60 for CBF, and 60:40 for CMRG. The active:basal CMRO2 distribution corroborates earlier data and shows that relative to CMRO2, the active compartment is underperfused with a lower oxygen-glucose index compared with the basal compartment.

Acute cerebral blood flow response to dopamine-induced hypertension after subarachnoid hemorrhage.

The effects of dopamine-induced hypertension on local cerebral blood flow (CBF) were investigated in 13 patients suspected of suffering clinical vasospasm after aneurysmal subarachnoid hemorrhage (SAH). The CBF was measured in multiple vascular territories using xenon-enhanced computerized tomography (CT) with and without dopamine-induced hypertension. A territorial local CBF of 25 ml/100 gm/min or less was used to define ischemia and was identified in nine of the 13 patients. Raising mean arterial blood pressure from 90 +/- 11 mm Hg to 111 +/- 13 mm Hg (p < 0.05) via dopamine administration increased territorial local CBF above the ischemic range in more than 90% of the uninfarcted territories identified on CT while decreasing local CBF in one-third of the nonischemic territories. Overall, the change in local CBF after dopamine-induced hypertension was correlated with resting local CBF at normotension and was unrelated to the change in blood pressure. Of the 13 patients initially suspected of suffering clinical vasospasm, only 54% had identifiable reversible ischemia. The authors conclude that dopamine-induced hypertension is associated with an increase in flow in patients with ischemia after SAH. However, flow changes associated with dopamine-induced hypertension may not be entirely dependent on changes in systemic blood pressure. The direct cerebrovascular effects of dopamine may have important, yet unpredictable, effects on CBF under clinical pathological conditions. Because there is a potential risk of dopamine-induced ischemia, treatment may be best guided by local CBF measurements.

The effect of hypothermia on the incidence of delayed traumatic intracerebral hemorrhage.

Hypothermia has been shown to cause coagulation abnormalities, primarily related to platelet dysfunction. We reviewed coagulation function and the incidence of delayed traumatic intracerebral hemorrhage in a series of 36 patients with severe head injuries (Glasgow Coma Scale 3-7) enrolled in a prospective, randomized, clinical trial of therapeutic moderate hypothermia. Patients were randomized to a normothermic group (n = 16) or to a group cooled to 32 to 33 degrees C within 6 hours of injury (n = 20). Prothrombin times, partial thromboplastin times, and platelet counts were obtained in the emergency room and then again within 24 hours of randomization. Delayed traumatic intracerebral hemorrhage occurred in 6 of 20 (30%) hypothermic patients and 5 of 16 (31%) normothermic patients. In the hypothermic group, 9 of 17 patients had an increased prothrombin time during hypothermic therapy, as opposed to 11 of 16 in the normothermic group during the corresponding time period. The partial thromboplastin time was prolonged in 2 of 17 hypothermic patients and 2 of 16 normothermic patients. Three patients in the hypothermic group and one in the normothermic group developed thrombocytopenia (a platelet count of less than 100,000). There were no significant differences between the two groups in the incidence of delayed traumatic intracerebral hemorrhage, in measured coagulopathy, or in the mean values of measured coagulation parameters. Although the possibility of a hypothermia-induced coagulopathy has not yet been excluded, the short-term use of hypothermia does not appear to increase the risk for intracranial hemorrhagic complications in head injuries.

Local cerebral blood flow measured by xenon-enhanced CT during cryogenic brain edema and intracranial hypertension in monkeys.

We developed a closed-skull model of freeze injury-induced brain edema, a model classically thought to produce vasogenic edema, and observed the natural course of changes in edema and blood flow using xenon-enhanced computed tomography (CT) in five rhesus monkeys before and for up to 6 h post insult. Intracranial pressure (ICP) gradually rose throughout the duration of the experiment. CT scans and CBF images permitted direct observation of the evolution of the lesion and revealed early ischemia in the periphery of the injury zone that progressed over time in association with edema. Frequency histogram analysis of local CBF (ICBF) demonstrated subtle but potentially important changes in distribution of ICBF between and within hemispheres at various times post insult. Changes in ICBF distribution were phasic and dissociated from increases in ICP in the latter stages of injury. The Xe/CT CBF method can be used to evaluate the effects of injury and therapy on CBF in this and other models of acute brain injury.

The use of moderate therapeutic hypothermia for patients with severe head injuries: a preliminary report.

Animal research suggests that moderate therapeutic hypothermia may improve outcome after a severe head injury, but its efficacy has not been established in humans. The authors randomly assigned 40 consecutively treated patients with a severe closed head injury (Glasgow Coma Scale score 3 to 7) to either a hypothermia or a normothermia group. Using cooling blankets and cold saline gastric lavage, patients in the hypothermia group were cooled to 32 degrees to 33 degrees C (brain temperature) within a mean of 10 hours after injury, maintained at that temperature for 24 hours, and rewarmed to 37 degrees to 38 degrees C over 12 hours. Patients in the normothermia group were maintained at 37 degrees to 38 degrees C during this time. Deep-brain temperatures were monitored directly and used for all temperature determinations. Intracranial pressure (ICP), cerebral blood flow (CBF), and cerebral metabolic rate for oxygen (CMRO2) were measured serially for all patients. Hypothermia significantly reduced ICP (40%) and CBF (26%) during the cooling period, and neither parameter showed a significant rebound increase after patients were rewarmed. Compared to the normothermia group, the mean CMRO2 in the hypothermia group was lower during cooling and higher 5 days after injury. Three months after injury, 12 of the 20 patients in the hypothermia group had moderate, mild, or no disabilities; eight of the 20 patients in the normothermia group had improved to the same degree. Both groups had a similar incidence of systemic complications, including cardiac arrhythmias, coagulopathies, and pulmonary complications. It is concluded that therapeutic moderate hypothermia is safe and has sustained favorable effects on acute derangements of cerebral physiology and metabolism caused by severe closed head injury. The trend toward better outcome with hypothermia may indicate that its beneficial physiological and metabolic effects limit secondary brain injury.

Giardia intestinalis: detection of major genotypes by restriction analysis of gene amplification products.

The polymerase chain reaction (PCR) has been used to amplify a 0.52 kb segment of Giardia intestinalis DNA, using primers specific for nucleotide sequences conserved within two genes (tsp11 and tsa417) that encode homologous, cysteine-rich trophozoite surface proteins. Using products amplified from axenic isolates belonging to genetic groups I and II (defined on the basis of allozyme electrophoresis data), restriction endonuclease analysis revealed both tsp11-like and tsa417-like fragments within all samples. The study also identified among the amplification products of group II organisms an additional fragment, containing a novel PstI site, that is not detected in the reaction products of group I isolates. The recovery of three distinct PCR products from each group II isolate was verified by cloning the fragments into the plasmid vector pGEM-7. Fragments containing the new PstI site possess the ClaI site common to both tsp11 and tsa417-like fragments, but they lack the HindIII site which characterizes tsp11-like fragments and also lack the PstI and KpnI sites which characterize tsa417-like fragments. Spot-blot analyses using cloned fragments of all three types as probes showed strong homologous hybridization but weak heterologous hybridization, indicating that each type differs substantially in nucleotide sequence from the others. Because the samples of Giardia DNA used in the PCR were purified from cultures that had been established from single trophozoites, the data indicate that individual trophozoites belonging to genetic group II possess three homologous genes defined by these related fragments. The presence of a PstI site in the amplified segment of the newly-discovered third gene of group II organisms provides a simple diagnostic means of differentiating group I and II isolates.

Effect of stable xenon inhalation on internal carotid artery blood flow in unanesthetized monkeys.

Stable xenon (Xe) gas, at inspired concentrations above 30%, reportedly increased cerebral blood flow (CBF) in animals and humans. An unpredictable Xe-induced elevation of CBF could result in erroneous CBF values being measured by Xe-enhanced computed tomography (Xe-CT). In order to detect a potentially rapid and transient effect of Xe on CBF, estimations of supratentorial CBF were obtained by Doppler flow probes chronically and bilaterally implanted on the internal carotid arteries of five adult monkeys. The unanesthetized monkeys with a clear plastic helmet were equilibrated for 15 min on a control gas (33% N2/67% O2) randomly exposed for 5 min to gas mixtures of either 33% Xe/67% O2 or 10% CO2/23% N2/67% O2. The mean control bilateral internal carotid artery blood flow (ICABF) was 23 +/- 10 ml/min (mean +/- SD), mean arterial pressure (MAP) was 101 +/- 13 mm Hg, and PaCO2 was 34 +/- 6 mm Hg. Inhalation of 33% Xe in O2 did not change the ICABF, MAP, or PaCO2. Inhalation of 10% CO2 in O2 increased the ICABF to 39 +/- 15 ml/min (p <0.001), MAP to 112 +/- 16 mm Hg (p <0.05), and PaCO2 to 54 +/- 5 mm Hg (p <0.001). The lack of change in ICABF and PaCO2 with 32% Xe inhalation suggests that a clinically relevant change in CBF is unlikely.

Effect of 80% Xe on whole brain blood flow and metabolism in awake monkeys.

We previously reported that 33% xenon (Xe) did not activate cerebral blood flow (CBF) and metabolism in monkeys as it appears to do in humans. However, monkeys may be less sensitive to Xe than humans are, which would explain the discrepancy in the results, but no one has studied the effects of higher concentrations of Xe on CBF and metabolism in monkeys. Therefore, we studied the effect of 80% Xe on whole-brain CBF, cerebral metabolic rate for oxygen (CMRO2) and glucose (CMRG) in five awake rhesus monkeys. Platinum microelectrodes and catheters inserted into the torcular Herophili were used to measure H2 clearance CBF, and to withdraw cerebral venous blood for O2 and glucose analysis. Cerebral variables were measured after 15 min exposure to 80% N2/20% O2 followed by 80% Xe/20% O2. Eighty percent Xe compared with 80% N2 increased (p <0.01) CBF by 52.7% from 74 +/- 16 to 113 +/- 25 (mean +/- SD) ml 100 g(-1)/min(-1), CBF/CMRO by 154% from 13 to 33, and decreased (p <0.05) CMRO2 by 39.3% from 6.1 +/- 0.9 to 3.7 +/- 0.8 ml 100 g(-1)/min(-1) and CMRG by 52.4% from 8.4 +/- 2.6 to 4.0 +/- 2.0 mg 100 g(-1)/min(-1). Electroencephalogram frequency decreased from a predominantly alpha to dagger rhythm in three of five monkeys. The 40 and 50% reduction in CMRO2 and CMRG, respectively, by 80% Xe suggests an anesthetic effect at this dose in the rhesus monkey but also activates CBF by 50%.

Effect of 33% xenon inhalation on whole-brain blood flow and metabolism in awake and fentanyl-anesthetized monkeys.

BACKGROUND AND PURPOSE: Despite the documented diagnostic value of local cerebral blood flow maps by xenon-enhanced computed tomography, reports of cerebral blood flow activation by inhaled 33% Xe raised concerns about the method's safety and accuracy. We evaluated the effect of 33% Xe inhalation on cerebral blood flow and cerebral metabolic rates for oxygen and glucose in four awake and six fentanyl-anesthetized rhesus monkeys. METHODS: Platinum microelectrodes and catheters in the torcular Herophili were used to measure cerebral blood flow by hydrogen clearance, and oxygen and glucose concentrations. Cerebral variables were measured after 5 and 35 minutes of exposure to room air followed randomly by 67% O2 in 33% N2 or Xe. Five- and 35-minute measurements were combined because the duration of exposure had no effect. RESULTS: In awake monkeys, 33% Xe compared with 33% N2 reduced (p less than 0.05) cerebral blood flow from 75 +/- 12 to 66 +/- 9 (mean +/- SD) ml.100 g-1.min-1 and oxygen consumption from 6.1 +/- 0.7 to 5.1 +/- 0.6 ml.100 g-1.min-1. In fentanyl-anesthetized monkeys, cerebral variables during 33% N2 versus 33% Xe were cerebral blood flow, 84 +/- 26 versus 79 +/- 23 ml.100 g-1.min-1; oxygen consumption, 5.0 +/- 0.7 versus 4.9 +/- 0.5 ml.100 g-1.min-1; and glucose consumption, 8.4 +/- 1.9 versus 7.9 +/- 2.0 mg.100 g-1.min-1. CONCLUSIONS: In awake monkeys, 33% Xe reduced rather than activated cerebral blood flow and oxygen consumption by 12% and 16%, respectively; it had no effect in fentanyl-anesthetized monkeys.

CBF measured by Xe-CT: approach to analysis and normal values.

Normal reference values and a practical approach to CBF analysis are needed for routine clinical analysis and interpretation of xenon-enhanced computed tomography (CT) CBF studies. We measured CBF in 67 normal individuals with the GE 9800 CT scanner adapted for CBF imaging with stable Xe. CBF values for vascular territories were systematically analyzed using the clustering of contiguous 2-cm circular regions of interest (ROIs) placed within the cortical mantle and basal ganglia. Mixed cortical flows averaged 51 +/- 10ml.100g-1.min-1. High and low flow compartments, sampled by placing 5-mm circular ROIs in regions containing the highest and lowest flow values in each hemisphere, averaged 84 +/- 14 and 20 +/- 5 ml.100 g-1.min-1, respectively. Mixed cortical flow values as well as values within the high flow compartment demonstrated significant decline with age; however, there were no significant age-related changes in the low flow compartment. The clustering of systematically placed cortical and subcortical ROIs has provided a normative data base for Xe-CT CBF and a flexible and uncomplicated method for the analysis of CBF maps generated by Xe-enhanced CT.