Cerebral blood flow, arteriovenous oxygen difference, and outcome in head injured patients.

Cerebral blood flow (CBF) and other physiological variables were measured repeatedly for up to 10 days after severe head injury in 102 patients, and CBF levels were related to outcome. Twenty five of the patients had a reduced CBF [mean (SD) 0.29 (0.05) ml/g/min]; 47 had a normal CBF, (0.41 (0.10) ml/g/min); and 30 had a raised CBF (0.62 (0.14) ml/g/min). Cerebral arteriovenous oxygen differences were inversely related to CBF and averaged 2.1 (0.7) mumol/ml in the group with reduced CBF, 1.9 (0.5) mumol/ml in the group with normal CBF, and 1.6 (0.4) mumol/ml in the group with raised CBF. Patients with a reduced CBF had a poorer outcome than patients with a normal or raised CBF. Mortality was highest in patients with a reduced CBF, and was 32% at three months after injury, whereas only 21% of the patients with a normal CBF and 20% of the patients with a raised CBF died. There were no differences in the type of injury, initial score on the Glasgow Coma Scale, mean intracranial pressure (ICP), highest ICP, or the amount of medical treatment required to keep the ICP less than 20 mm Hg in each group. Systemic factors did not significantly contribute to the differences in CBF among the three groups. A logistic regression model of the effect of CBF on neurological outcome was developed. When adjusted for variables which were found to be significant confounders, including age, initial Glasgow Coma Score, haemoglobin concentration, cerebral perfusion pressure and cerebral metabolic rate of oxygen, a reduced CBF remained significantly associated with an unfavourable neurological outcome.     

Comparison of two dimensional and three dimensional CBF measurements in stroke patients

The purpose of this study is to compare the detectability of the reduction in cerebral blood flow (CBF) using the two versus the three dimensional technique of CBF measurement. Both techniques were simultaneously carried out 85 times on 52 stroke patients. In the two dimensional technique, CBF was measured by the Xe-133 inhalation method and the value was calculated by the initial slope index. In the three dimensional technique, CBF was measured by single photon emission CT with Xe-133 inhalation method. CBF reduction was studied in the middle cerebral artery (MCA) territory on a CBF map in both techniques. Additionally, mean CBF was also calculated for the same territory. On the CBF map, the CBF reduction was shown in 25 of 85 measurements with the two dimensional technique and in 41 of 85 with the three dimensional technique. In comparing the imagings of both techniques, the CBF reduction seen extensively along the cortical surface and in the entire MCA territory with the three dimensional technique was also detected with the two dimensional technique. However, focal CBF reduction observed at the cortical surface and in the deep cerebral tissue with the three dimensional technique was not detected with the two dimensional technique. In order to evaluate both techniques quantitatively, we calculated the ratio of the mean CBF difference between the MCA territories of both hemispheres to mean CBF in the non-affected MCA territory. This ratio represented the asymmetry index. Firstly, the relationship between asymmetry index and the imaging of CBF reduction on the CBF map was studied.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cerebral blood flow in systemic lupus erythematosus with or without cerebral complications

We measured mean cerebral blood flow (CBF) in 25 lupus patients using the xenon-133 method. The CBF was normal in lupus patients without cerebral disease and also in CNS lupus patients in remission. The CBF was lower than normal during bouts of cerebral lupus (p less than 0.001). Repeat studies showed a stereotyped pattern consisting of depressed CBF during exacerbation of CNS disease and normalization of CBF during remission (p less than 0.01). These results show that CBF is a sensitive indicator of activity of CNS disease and that the direction of change in CBF reflects the clinical course of CNS lupus.     

Cerebral blood flow and CO2 reactivity in patients with transient ischemic attack]

To elucidate the changes in cerebral blood flow (CBF) and CO2 reactivity in patients with transient ischemic attack (TIA), 10 patients with TIA and 5 healthy adults (controls) underwent two consecutive CBF measurements (i.e. the first measurement during room air inhalation and the second measurement during 5%CO2 inhalation). Hemispheric mean CBF was determined by each CBF measurement using 133Xenon inhalation method. CO2 reactivity was evaluated by analysing delta CBF (= mean CBF during hypercapnea-mean CBF at rest) and delta CBF/delta PaCO2. The resting mean CBF values in the bilateral hemispheres (i.e. both of the affected and unaffected hemispheres) were significantly lower in TIA patients than controls (p less than 0.05). Inhalation of 5%CO2 significantly increased mean CBF in TIA patients bilaterally, however the mean CBF value during hypercapnea was again significantly lower in TIA patients than controls (p less than 0.05). CO2 reactivity in TIA patients was not significantly different from controls (p greater than 0.05). The result demonstrated that TIA patients have a chronic and global cerebral oligemia with normal CO2 reactivity. The chronic and global cerebral oligemia may develop a transient ischemic neurological symptom by being superimposed with local decrease of CBF.     

Cerebral blood flow responses to inhaled carbon dioxide in schizophrenia

Carbon dioxide (CO2) is a potent cerebrovasodilator; even mild changes in CO2 are associated with marked changes in cerebral blood flow (CBF). We measured CBF before and after 5% CO2 inhalation in 19 medicated patients with schizophrenia and 16 normal volunteers. Another group of 16 volunteers had 2 CBF measurements under resting conditions. Although both patients and controls showed marked CBF increase during CO2 inhalation, the CBF response was significantly less in the patients. Change in CBF per mm of CO2 was lower in the patients. The second group of controls did not show significant differences between the 2 resting CBF measurements.     

Cerebral blood flow increases evoked by electrical stimulation of rat cerebellar cortex: relation to excitatory synaptic activity and nitric oxide synthesis

The purpose of this study was to examine mechanisms involved in the coupling of neuronal activity to cerebral blood flow (CBF). CBF was measured in rat cerebellum using laser-Doppler flowmetry during stimulus-evoked neuronal activity and related to the distribution of the extracellular field potential. Local electrical stimulation of the cerebellar cortex activated a narrow beam of parallel fibers (PFs) 100 μm across and evoked increases of CBF along (On-B) and perpendicular (Off-B) to the beam. Increases of CBF and field potentials were recorded for a distance of up to 1500 μm along the activated beam, and perpendicular to the beam, in a zone approximately 1000 μm wide, i.e. about 10 times wider than the zone in which synaptic excitation took place. CBF increased as a function of stimulus frequency up to 75 Hz, the response being larger On-B than Off-B. TTX abolished both the field potentials and the CBF responses at all frequencies, suggesting that action potentials were mechanistically related to the evoked CBF increases. CBF changes were unchanged by picrotoxin, a blocker of GABA_A receptors, consistent with the idea that inhibitory synaptic activity does not contribute to CBF increases. The latency to the CBF rise was much shorter On-B than Off-B for the same distance from the stimulating electrode. This may suggest that the CBF response Off-B is dependent on diffusion of vasoactive substances from neuronal structures activated by the parallel fibers On-B. Nitric oxide (NO) synthase inhibition withN^G-nitro-l-Arginine increased the time latency to onset of CBF rise by 2–4 times and attenuated the evoked CBF increase by approximately 50%. Sodium nitroprusside, a NO donor, increased baseline CBF, but did not reverse the effects ofl-NNA. Thus the initial part of the evoked CBF rise is probably mediated by NO, which also contributes to the later part of the response. This study provides insight into the distribution and mechanism of neurally evoked increases of CBF, of putative importance for the interpretation of activation studies in animals and humans.     

Changes in human cerebral blood flow and cerebral blood volume during hypercapnia and hypocapnia measured by positron emission tomography.

Hypercapnia induces cerebral vasodilation and increases cerebral blood flow (CBF), and hypocapnia induces cerebral vasoconstriction and decreases CBF. The relation between changes in CBF and cerebral blood volume (CBV) during hypercapnia and hypocapnia in humans, however, is not clear. Both CBF and CBV were measured at rest and during hypercapnia and hypocapnia in nine healthy subjects by positron emission tomography. The vascular responses to hypercapnia in terms of CBF and CBV were 6.0 +/- 2.6%/mm Hg and 1.8 +/- 1.3%/mm Hg, respectively, and those to hypocapnia were -3.5 +/- 0.6%/mm Hg and -1.3 +/- 1.0%/mm Hg, respectively. The relation between CBF and CBV was CBV = 1.09 CBF0.29. The increase in CBF was greater than that in CBV during hypercapnia, indicating an increase in vascular blood velocity. The degree of decrease in CBF during hypocapnia was greater than that in CBV, indicating a decrease in vascular blood velocity. The relation between changes in CBF and CBV during hypercapnia was similar to that during neural activation; however, the relation during hypocapnia was different from that during neural deactivation observed in crossed cerebellar diaschisis. This suggests that augmentation of CBF and CBV might be governed by a similar microcirculatory mechanism between neural activation and hypercapnia, but diminution of CBF and CBV might be governed by a different mechanism between neural deactivation and hypocapnia.     

Impaired cerebral circulation and the effect of glycerol infusion in the acute stage of hypertensive intracerebral hematoma

The purpose of the present study was to clarify the mechanism of reduction in cerebral blood flow (CBF) in the acute stage of hypertensive intracerebral hematoma and the effect of glycerol infusion on the reduced CBF. We examined 55 cases. Thirty-eight cases showed putaminal hematoma and 17 presented thalamic hematoma. The range of consciousness was from alert to stupor. CBF was measured by single photon emission CT with Xe-133 inhalation within five days after the onset of the hemorrhage. A CBF map was obtained at a slice 5 cm above the OM-line and mean CBF of the affected and non-affected hemispheres was calculated. In 20 of 55 cases, 500 ml of glycerol was intravenously infused for 60 minutes and thereafter CBF was measured again. Epidural pressure was also recorded at the affected frontal area during glycerol infusion in three of the 20 cases. CBF reduced more profoundly in the area around the hematoma on the CBF map. Mean CBF of the affected hemisphere was negatively correlated with the volume of hematoma by a quadratic regression. After glycerol infusion, 13 of 20 cases showed a significant increase in mean CBF of the affected hemisphere, while the other seven cases showed no increase. Mean CBF increased with a higher percentage in cases with ventricular hemorrhage than without ventricular hemorrhage. In three cases where epidural pressure was measured during glycerol infusion, mean CBF increased and epidural pressure decreased. The increase in mean CBF was proportional to a rise in perfusion pressure calculated as pressure difference between mean systemic arterial pressure and mean epidural pressure, indicating impaired autoregulation in these cases.(ABSTRACT TRUNCATED AT 250 WORDS)     

A comparison of cerebral blood flow during basal, hypotensive, hypoxic and hypercapnic conditions between normal and streptozotocin diabetic rats

This study was undertaken to determine the differences (if any) in cerebral blood flow (CBF) between streptozotocin (STZ) diabetic and normal rats. CBF was studied in connection with episodes of hypoxia, hypercapnia and hypotension as compared to the basal condition. Overall basal CBF rates in streptozotocin diabetic rats were significantly higher than in normal animals. However, initial basal flow rates prior to the first challenge were insignificantly higher in the STZ diabetic group. The higher CBF rate in STZ diabetics was also seen during the peak flows of the hypoxic and hypercapnic challenges. Furthermore, although overall CBF decreased for both the normal and STZ diabetic groups during hypotension, higher CBFs were observed in the STZ diabetic group during this challenge. The percent increase in CBF above control resulting from hypoxia or hypercapnia and the changes in CBF resulting from hypotension were not significantly different in the STZ diabetic and normal groups. The results indicate that the STZ diabetic rat regulates CBF in the same manner as the normal rat in response to hypoxia, hypercapnia and hypertension. The STZ diabetic rat executes these CBF responses at a slightly higher CBF rate. In view of the finding that the regulation of CBF is unaltered in the STZ diabetic animal, it is hypothesized that the associated hyperglycemia may be the causative agent for the cerebral ischemic susceptibility associated with long-term diabetes mellitus rather than a failure of CBF regulation.     

The effects of etomidate in the cat middle cerebral artery occlusion model of brain ischaemia: An experimental study

The effects of etomidate on focal cerebral ischaemia following transorbital occlusion of the cat middle cerebral artery were investigated. Etomidate had no effect on CBF before or after onset of ischaemia by comparison with controls, but caused a greater fall in CBF in cats with high preocclusion or initial ischaemic CBF than in those in which CBF was lower. There were more sustained rises in Kp on SG. The established flow threshold for water accumulation was lost; more gyri with CBF above and fewer gyri with CBF below the flow threshold accumulated water. The relationship between mean occlusion CBF and in vitro GABA uptake was lost; uptakes from MC were lower and from SG and EG higher than expected. In the ischaemic penumbra there was a trend towards reduction in CBF, disruption of ion homeostasis and cerebral oedema formation, whilst in areas of lower flow there was some recovery of GABA uptake and less cerebral oedema following administration of etomidate.     

Simultaneous blood oxygenation level-dependent and cerebral blood flow functional magnetic resonance imaging during forepaw stimulation in the rat.

The blood oxygenation level-dependent (BOLD) contrast mechanism can be modeled as a complex interplay between CBF, cerebral blood volume (CBV), and CMRO2. Positive BOLD signal changes are presumably caused by CBF changes in excess of increases in CMRO2. Because this uncoupling between CBF and CMRO2 may not always be present, the magnitude of BOLD changes may not be a good index of CBF changes. In this study, the relation between BOLD and CBF was investigated further. Continuous arterial spin labeling was combined with a single-shot, multislice echo-planar imaging to enable simultaneous measurements of BOLD and CBF changes in a well-established model of functional brain activation, the electrical forepaw stimulation of alpha-chloralose-anesthetized rats. The paradigm consisted of two 18- to 30-second stimulation periods separated by a 1-minute resting interval. Stimulation parameters were optimized by laser Doppler flowmetry. For the same cross-correlation threshold, the BOLD and CBF active maps were centered within the size of one pixel (470 microm). However, the BOLD map was significantly larger than the CBF map. Measurements taken from 15 rats at 9.4 T using a 10-millisecond echo-time showed 3.7 +/- 1.7% BOLD and 125.67 +/- 81.7% CBF increases in the contralateral somatosensory cortex during the first stimulation, and 2.6 +/- 1.2% BOLD and 79.3 +/- 43.6% CBF increases during the second stimulation. The correlation coefficient between BOLD and CBF changes was 0.89. The overall temporal correlation coefficient between BOLD and CBF time-courses was 0.97. These results show that under the experimental conditions of the current study, the BOLD signal changes follow the changes in CBF.     

Semi-quantitative CBF and CBF ratios obtained using perfusion-weighted MR imaging

To clarify the utility of semi-quantitative cerebral blood flow (CBF) measurements using perfusion-weighted MR imaging (PWI), a comparison of this method with quantitative CBF obtained using PET was conducted in 10 patients with chronic occlusive cerebrovascular disease and unilateral occlusion of the cerebral artery. Semi-quantitative CBF obtained using PWI and quantitative CBF obtained using PET showed no statistically significant correlation. The CBF ratios of the affected side relative to the contralateral unaffected side obtained using PWI and PET were 0.94 +/- 0.22 and 0.88 +/- 0.19, respectively. A statistically significant positive correlation was obtained between these ratios (p < 0.01). The CBF ratio, but not the semi-quantitative CBF, obtained using PWI has a potential to detect changes in the CBF.     

Autoregulation of cerebral blood flow in experimental focal brain ischemia

The relationship between systemic arterial pressure (SAP) and neocortical microcirculatory blood-flow (CBF) in areas of focal cerebral ischemia was studied in 15 spontaneously hypertensive rats (SHRs) anesthetized with halothane (0.5%). Ischemia was induced by ipsilateral middle cerebral artery/common carotid artery occlusion and CBF was monitored continuously in the ischemic territory using laser-Doppler flowmetry during manipulation of SAP with I-norepinephrine (hypertension) or nitroprusside (hypotension). In eight SHRs not subjected to focal ischemia, we demonstrated that 0.5% halothane and the surgical manipulations did not impair autoregulation. Autoregulation was partly preserved in ischemic brain tissue with a CBF of greater than 30% of preocclusion values. In areas where ischemic CBF was less than 30% of preocclusion values, autoregulation was completely lost. Changes in SAP had a greater influence on CBF in tissue areas where CBF ranged from 15 to 30% of baseline (9% change in CBF with each 10% change in SAP) than in areas where CBF was less than 15% of baseline (6% change in CBF with each 10% change in SAP). These findings demonstrate that the relationship between CBF and SAP in areas of focal ischemia is highly dependent on the severity of ischemia. Autoregulation is lost in a gradual manner until CBF falls below 30% of normal. In areas without autoregulation, the slope of the CBF/SAP relationship is inversely related to the degree of ischemia.     

Analysis of the effect of bilateral sympathetic stimulation of cerebral and cephalic blood flow in the dog

Unilateral stimulation of the cervical sympathetic in dogs had no effect on cerebral blood flow (CBF) measured by the venous outflow technique. Since this technique measured CBF from both cerebral hemispheres, small changes induced by unilateral stimulation could have been masked by a large constant CBF measured from the contralteral hemisphere. To test this possibility the effect of simultaneous bilateral sympathetic stimulation was studied when the dog was breathing either normal air or a gas mixture of 10%CO2. During normocapnia, no changes in CBF occurred; during hypercapnia CBF increased 19% following passively the increase in blood pressure. These data indicate that bilateral stimulation of extracranial sympathetic nerves does not exert a significant effect on CBF. We show mathematically and experimentally that unoccluded anastomses will cause CBF to appear to decrease in response to sympathetic stimulation. This may explain why others have observed changes in CBF during sympathetic stimulation.     

The influence of haematocrit and blood glucose on cerebral blood flow in normal and in diabetic rats.

Cerebral blood flow (CBF) was measured at varying haematocrit values in 8 streptozotocin-diabetic and in 7 control rats using the intracarotid 133Xe technique. A hyperbolic relationship between CBF and haematocrit was established for the individual rats in both groups. Diabetic animals showed a preserved CBF response to changes to haematocrit. In 10 normal rats, CBF was measured during acute hyperglycaemia induced by intraperitoneal glucose injection. A significant, inverse correlation was found between CBF and blood glucose. We conclude that the CBF response to changes in haematocrit and thereby in pO2 is preserved in experimental diabetes. Secondly, in acute hyperglycaemia CBF varies inversely with blood glucose, by mechanisms not fully understood.     

Cerebral blood flow variations in CNS lupus

We studied the patterns of cerebral blood flow (CBF), over time, in patients with systemic lupus erythematosus and varying neurologic manifestations including headache, stroke, psychosis, and encephalopathy. For 20 paired xenon-133 CBF measurements, CBF was normal during CNS remissions, regardless of the symptoms. CBF was significantly depressed during CNS exacerbations. The magnitude of change in CBF varied with the neurologic syndrome. CBF was least affected in patients with nonspecific symptoms such as headache or malaise, whereas patients with encephalopathy or psychosis exhibited the greatest reductions in CBF. In 1 patient with affective psychosis, without clinical or CT evidence of cerebral ischemia, serial SPECT studies showed resolution of multifocal cerebral perfusion defects which paralleled clinical recovery.     

Relative hypoperfusion in rat cerebral cortex during recurrent seizures.

Focal cortical CBF and oxygenation were measured in rats during repetitive seizures to determine whether CBF is maintained above a critical level for adequate delivery of O2. Cerebral oxygenation was determined by measuring relative changes in the oxidation/reduction level of cytochrome aa3 and CBF was measured by the washout of H2. During early seizures, cortical CBF increased to 350% of control and cortical oxygenation also rose markedly. During later seizures, both the increases in CBF and in cortical oxygenation were attenuated progressively. This was accompanied also by attenuation of the associated increases in MABP. Cortical oxygenation decreased during a seizure if the increase in CBF failed to exceed 150-200% of control, defining the critical CBF value. Ventilating the rats on 97% O2 resulted in restoration of the seizure-associated increases in cortical oxygenation in 50% of the cases. The elevation of inspired O2 was effective only if CBF increased once again above 150-200% of control, confirming that the critical CBF lies within this range of values. We conclude that CBF must rise greater than 200% of control levels to provide sufficient O2 to meet the enhanced metabolic requirements of repetitive seizures.     

The effects of etomidate in the cat middle cerebral artery occlusion model of brain ischaemia. An experimental study

The effects of etomidate on focal cerebral ischaemia following transorbital occlusion of the cat middle cerebral artery were investigated. Etomidate had no effect on CBF before or after onset of ischaemia by comparison with controls, but caused a greater fall in CBF in cats with high preocclusion or initial ischaemic CBF than in those in which CBF was lower. There were more sustained rises in Kp on SG. The established flow threshold for water accumulation was lost; more gyri with CBF above and fewer gyri with CBF below the flow threshold accumulated water. The relationship between mean occlusion CBF and in vitro GABA uptake was lost; uptakes from MG were lower and from SG and EG higher than expected. In the ischaemic penumbra there was a trend towards reduction in CBF, disruption of ion homeostasis and cerebral oedema formation, whilst in areas of lower flow there was some recovery of GABA uptake and less cerebral oedema following administration of etomidate.     

Cerebral blood flow response to propranolol in streptozotocin diabetic rats

The influence of propranolol on cerebral blood flow (CBF) was tested in streptozotocin diabetic rats and in control animals. Resting CBF values were 40% lower in the diabetic rats compared with controls. Intravenous injection of propranolol (2 mg kg-1) decreased CBF significantly in the control group; the CBF decreased for 15 min after propranolol injection and returned to baseline values after 90 min. In the diabetic rats, the CBF declined steadily but this decrease did not reach significance, even after 90 min. Impaired beta-adrenergic mechanisms may be an important factor in the CBF alterations which occur in diabetes mellitus. Further, it is suggested that an impaired CBF response may play a role in CNS lesions in diabetic patients treated with beta antagonists.