Cerebral blood volume,blood flow,and oxygen metabolism in cerebral ischaemia and subarachnoid haemorrhage: An in-vivo study using positron emission tomography

Summary A characteristic sequence of metabolic and haemodynamic changes has been shown to occur in the brain as cerebral perfusion pressure is reduced in experimental animals. Increased cerebral blood volume (CBV) occurs initially, followed by a fall in blood flow (CBF) and, finally, a fall in oxygen metabolism (CMRO₂). By measuring CBV, CBF, and CMRO₂ with positron emission tomography in patients with vasospasm associated with subarachnoid haemorrhage and in patients with arteriosclerotic occlusion or stenosis of extraparenchymal cerebral arteries, we have demonstrated the presence of similar changes distal to such lesions in man. These findings suggest the presence of a local decrease in perfusion pressure. This study demonstrates the utility of positron emission tomography in the assessment of cerebral circulation and metabolism in man. Measurements of regional CBV must be included for a complete assessment of the dynamics of the cerebral circulation.Presented at the Symposium on Cerebral Veins, Graz, Austria, 1982.     

Cerebral circulation and metabolism in the acute stage of subarachnoid hemorrhage

OBJECT: The mechanism of reduction of cerebral circulation and metabolism in patients in the acute stage of aneurysmal subarachnoid hemorrhage (SAH) has not yet been fully clarified. The goal of this study was to elucidate this mechanism further. METHODS: The authors estimated cerebral blood flow (CBF), cerebral metabolic rate of oxygen (CMRO2), O2 extraction fraction (OEF), and cerebral blood volume (CBV) preoperatively in eight patients with aneurysmal SAH (one man and seven women, mean age 63.5 years) within 40 hours of onset by using positron emission tomography (PET). The patients' CBF, CMRO2, and CBF/CBV were significantly lower than those in normal control volunteers. However, OEF and CBV did not differ significantly from those in control volunteers. The significant decrease in CBF/CBV, which indicates reduced cerebral perfusion pressure, was believed to be caused by impaired cerebral circulation due to elevated intracranial pressure (ICP) after rupture of the aneurysm. In two of the eight patients, uncoupling between CBF and CMRO2 was shown, strongly suggesting the presence of cerebral ischemia. CONCLUSIONS: The initial reduction in CBF due to elevated ICP, followed by reduction in CMRO, at the time of aneurysm rupture may play a role in the disturbance of CBF and cerebral metabolism in the acute stage of aneurysmal SAH.     

The effect of ketanserin on cerebral blood flow and oxygen metabolism in healthy volunteers

Summary The effect of the anti-hypertensive agent ketanserin on average global cerebral blood flow (CBF) and average global cerebral oxygen metabolism (CMRO₂) was examined in 8 healthy volunteers. CBF and CMRO₂ were measured with the Kety-Schmidt technique before ketanserin administration (baseline) and after administration of 2 different doses of ketanserin intravenously (dose I: 10 mg bolus and an infusion of 6 mg/h; dose II: 20 mg bolus and an ifusion of 20 mg/ h). Baseline CBF and CMRO₂ were 60 and 3.6 ml/100 g/min, respectively, and were not changed by administration of ketanserin dose I. During administration of dose II, however, CBF fell to 52 ml/ 100 g/min (p=0.05) and CMRO₂ was reduced to 3.2 ml/100 g/min (p < 0.05).We conclude that when administered in a high dose, ketanserin has the ability to depress cerebral oxygen metabolism, but when administered in a clinically relevant dose ketanserin does not influence average global CBF or average global CMRO₂. Ketanserin could be a safe antihypertensive drug in neuroanaesthesia or in the neuro-intesive care unit.     

Prognosis in contre-coup intracranial haematomas — a clinical and radiological study of 63 patients

Summary Assessment of cerebral perfusion on patients with subarachnoid haemorrhage (SAH) in the Neurologic Intensive Care Unit is difficult since nuclear medicine imaging modalities capable of measuring cerebral blood flow (CBF) are not generally available. We performed 101 quantitative (ml/100g-min) bedside CBF measurements on 40 individual patients to correlate SAH grade with CBF and to assess the effect of surgical intervention on CBF. Global CBF (G-CBF) and bihemispheric CBF (B-CBF) asymmetry were correlated with the grade of SAH pre- and post-operatively.Data analysis showed that pre-operative patients with low grade SAH (Hunt and Hess grades 0 to 2) had higher mean G-CBF values [44.2±.71] than those with high grade SAH (Hunt and Hess grades 3 to 4): [mean G-CBF=34.1±1.7]. Post-surgery there was a significant improvement in G-CBF; CBF increased [5.3±1.07] in the group of patients with low grade SAH. Patients with high grade SAH showed no significant improvement in their G-CBF during the first week post-operatively compared to pre-operative values.We conclude that portable units capable of measuring bedside CBF values are useful in monitoring CBF changes in patients with SAH. Patients with low grade SAH have G-CBF within normal limits both pre-operatively and post-operatively, with a statistically significant increase in CBF during two weeks post-operatively. Patients with high grade SAH show no significant increase in CBF one week post-operatively compared to their pre-operative measures.     

Convenience of the computed tomography perfusion method for cerebral vasospasm detection after subarachnoid hemorrhage

BACKGROUND: Vasospasm is a frequent complication in the early clinical course after SAH. Although various methods have been used to measure cerebral perfusion including PET, SPECT, xenon CT, and TCD, these require the patients to remain still for a long period. In addition, TCD is operator dependent. The current study aimed to clarify the convenience of CTP for the assessment of cerebral vasospasm caused by SAH. METHODS: Nineteen patients with SAH aged 44 to 85 years (mean, 64 years) were recruited with informed consent. All patients were treated with the prevailing therapy and underwent CTP on days 6 to 9, followed by DSA and 3D-CTA to detect cerebral vasospasm. In each patient, we measured the MTT, CBF, and CBV. The reliability of CTP data was verified by comparing the data from CTP and xenon CT between the controls, and the average was calculated. Six ROIs were located symmetrically in the frontal, temporal, and occipital lobes. RESULTS: An MTT value more than 20% greater than the average indicated the progression of cerebral vasospasm, and patients with vasospasm-related infarcts exhibited an MTT more than 47% greater than the mean value (odds ratio, 50). Patients with delayed cerebral infarcts had a significantly lower mean CBF and CBV and higher MTT than patients who did not develop CI. CONCLUSION: Significant correlations between MTT and CBF values and neurovascular findings were obtained. Computed tomography perfusion can be performed in a short time and on a regular basis, and it therefore has the potential to identify cerebral vasospasm because of SAH.     

Effect of normal saline bolus on cerebral blood flow in regions with low baseline flow in patients with vasospasm following subarachnoid hemorrhage

OBJECT: Arterial vasospasm is the most common cause of delayed ischemic neurological deficits (DINDs) and one of the major causes of disability following subarachnoid hemorrhage (SAH). Current management of vasospasm involves intravascular volume expansion and hemodynamic augmentation with the goal of increasing cerebral blood flow (CBF). The purpose of this study was to examine the effects of volume expansion on regional (r)CBF in patients with DIND following SAH. METHODS: The authors measured quantitative rCBF on positron emission tomography (PET) scans in six patients with aneurysmal SAH who had developed clinical signs of vasospasm. All patients were kept in a euvolemic state prior to the onset of vasospasm. At the onset of vasospasm, global and rCBF were measured before and after the administration of a normal saline bolus of 15 ml/kg administered over 1 hour. Two patients then received saline infusions of 5 ml/kg x hr over the following 2 to 3 hours and underwent hourly serial CBF measurements. Global and rCBF data were calculated in each patient. The mean rCBF in areas with low flow at baseline (< or = 25 ml/[100 g x min]) increased from 19.1 +/- 3.0 to 29.9 +/- 9.7 ml/(100 g x min) (p = 0.02) with volume expansion. This change was sustained over the following 2 to 3 hours. Pulmonary capillary wedge pressure, mean arterial blood pressure, cardiac output, and central venous pressure did not change significantly during this intervention. CONCLUSIONS: In euvolemic patients with vasospasm, intravascular volume expansion with a normal saline bolus raised CBF in regions of the brain most vulnerable to ischemia.     

Cerebral blood flow and oxidative brain metabolism during and after moderate and profound arterial hypoxaemia

Summary In anaesthetized artificially ventilated dogs, the effect of graded arterial hypoxaemia on cerebral blood flow (CBF) and on the oxidative carbohydrate metabolism of the brain was tested. It is shown that the hypoxic vasodilatory influence on cerebral vessels is present even atmoderate systemic hypoxaemia, provided that PaCO₂ is kept within normal limits. At PaO₂ of about 50 Torr, CBF increased from 56.6 to 89.7 ml/100 g/min. With increasing cerebral hyperaemia (CBF increased to 110.9 ml/100 g/min, at PaO₂ of 30 Torr), CMRO₂ (4.2 ml/100 g/min) was not significantly raised above its normal level (4.7 ml/100 g/min) even with profound arterial hypoxaemia. This shows that CMRO₂ levels are poor indices of hypoxic hypoxia. A disproportionately high increase in cerebral glucose uptake (CMR glucose levels rose from 4.4 to 10.4 mg/100 g/min) and enhanced cerebral glycolysis (CMR lactate changed from 0.2 to 1.6 mg/100 g/min) at moderately reduced PaO₂ (50 Torr) indicated early metabolic changes which became more marked with further falls in arterial oxygen tension. However, 60 minutes after restoration of a normal PaO₂ level, CBF and brain metabolism were found to have completely recovered. It is concluded that a short period of profound systemic hypoxaemia does not produce long lasting metabolic and circulatory disorders of the brain provided the cerebral perfusion pressure does not vary, and is kept at normal levels.     

Quantitative cerebral blood flow and metabolism determination in the first 48 hours after severe head injury with a new dynamic spect device

SummaryObjective To determine cerebral blood flow (CBF) and metabolism in the acute phase after severe head injury by a new dynamic SPECT device using¹³³Xenon and to evaluate a possible role of CBF and metabolism in the determination of prognosis.Design Prospective studySetting General intensive care unit in a universitary teaching hospitalSubjects 23 severely head injured patients having CT scan and CBF determination, intracranial pressure (ICP) and jugular bulb oxygen saturation monitoring in the first 48 hours.Measurements and main results CBF varied from 18.0 to 60.0 ml/100 g/min. No correlation was found between early CBF and severity of trauma evaluated with the Glasgow Coma Score (GCS) (F = 2.151, p = 0.142) and between CBF and prognosis at 6 months evaluated with Glasgow outcome score (GOS) (F = 0.491, p = 0.622; r_s = 0.251, p = 0.246). CMRO₂ was depressed in relation to the severity of injury, specifically ranging from 0.9±0.5 ml/ 100 g/min in patients with GCS 3 to 1.7 ±0.8 ml/100 g/min in patients with GCS 6–7. In no patient with a CMRO₂ less than 0.8 ml/100 g/min was a good outcome observed. A significant correlation was found between GCS and GOS (r_s = 0.699, p = 0.0002), between CMRO₂ and GOS (F = 4.303, p = 0.031; r_s = 0.525, p = 0.013) and between AJDO₂ and GOS (F = 3.602, p = 0.046; r_s = 0.491, p = 0.017). Fronto-occipital ratio (F/O) of CBF distribution was significantly lower than normal values (²=18.658, p = 0.001) but did not correlate either with prognosis (² = 1.626, p = 0.443) or with severity (² = 1.913, p = 0.384).Conclusions CBF in the first 48 hours after trauma varies within a large range of values and is not correlated with severity and prognosis. Clinical evaluation with GCS and CMRO₂ are much more reliable indicators of severity of head trauma and have a significant role in the determination of prognosis. F/O ration is significantly altered from normal values confirming post-traumatic hypofrontalism but does not correlate with severity and prognosis.     

Disturbance of Cerebral Blood Flow Autoregulation in Hypertension is Attributable to Ischaemia Following Subarachnoid Haemorrhage in Rats: A PET Study

The effects of subarachnoid haemorrhage (SAH) on cerebral blood flow (CBF) autoregulation during induced hypertension were studied by positron emission tomography (PET) during chronic vasospasm in anaesthetized Sprague-Dawley rats. SAH was induced by intracisternal injection of autologous blood. In the control animals saline was injected instead. This method produced angiographical vasospasm of major arteries 48 h after injection. During this period, CBF was measured at each side of fronto-parietal and occipital sections using PET with or without induced hypertension. Mean arterial blood pressure (MABP) was increased from 94+/-2.4 to 140+/-0.3 mmHg by the injection of phenylephrine. An autoregulatory index (AI) expressed as delta CBF (%) per 10-mmHg increase in MABP was employed to analyse CBF response. SAH significantly reduced (p<0. 0001) basal CBF (ml/100 g/min) by 26.2% (control 60.0+/-1.9 n=24, SAH 44.3+/-4.5 n=20). A territorial CBF that decreased by 50% or more over the mean control value was used to define ischaemia and was identified in five out of 20 regions (25%) in the SAH group. AI (%/10-mmHg) was 13.5+/-2.4 in the control group (n=24). In the SAH group, AI decreased (p<0.05) to 4.5+/-2.5 in non-ischaemic areas (n=15), while in the ischaemic areas (n=5) AI increased (p<0.05) to 25.2+/-4.1. Since the spastic artery is intrinsically resistant to hypertension, the marked increase in CBF during hypertension can be attributable to ischaemia following SAH.     

Early cerebral circulatory disturbance in patients suffering subarachnoid hemorrhage prior to the delayed cerebral vasospasm stage: xenon computed tomography and perfusion computed tomography study

Subarachnoid hemorrhage (SAH) causes dynamic changes in cerebral blood flow (CBF), and results in delayed ischemia due to vasospasm, and early perfusion deficits before delayed cerebral vasospasm (CVS). The present study examined the severity of cerebral circulatory disturbance during the early phase before delayed CVS and whether it can be used to predict patient outcome. A total of 94 patients with SAH underwent simultaneous xenon computed tomography (CT) and perfusion CT to evaluate cerebral circulation on Days 1-3. Cerebral blood flow (CBF) was measured using xenon CT and the mean transit time (MTT) using perfusion CT and calculated cerebral blood volume (CBV). Outcome was evaluated with the Glasgow Outcome Scale (good recovery [GR], moderate disability [MD], severe disability [SD], vegetative state [VS], or death [D]). Hunt and Hess (HH) grade II patients displayed significantly higher CBF and lower MTT than HH grade IV and V patients. HH grade III patients displayed significantly higher CBF and lower MTT than HH grade IV and V patients. Patients with favorable outcome (GR or MD) had significantly higher CBF and lower MTT than those with unfavorable outcome (SD, VS, or D). Discriminant analysis of these parameters could predict patient outcome with a probability of 74.5%. Higher HH grade on admission was associated with decreased CBF and CBV and prolonged MTT. CBF reduction and MTT prolongation before the onset of delayed CVS might influence the clinical outcome of SAH. These parameters are helpful for evaluating the severity of SAH and predicting the outcomes of SAH patients.     

Comparison of moderate hyperventilation and mannitol for control of intracranial pressure control in patients with severe traumatic brain injury – a study of cerebral blood flow and metabolism

Summary Objective. To compare the respective effects of established measures used for management of traumatic brain injury (TBI) patients on cerebral blood flow (CBF) and cerebral metabolic rates of oxygen (CMRO₂), glucose (CMRGlc) and lactate (CMRLct). Methods. Thirty-six patients suffering from severe traumatic brain injury (TBI) were prospectively evaluated. In all patients baseline assessments were compared with that following moderate hyperventilation (reducing PaCO₂ from 36 ± 4 to 32 ± 4 mmHg) and with that produced by administration of 0.5 gr/kg mannitol 20% intravenously. Intracranial and cerebral perfusion pressure (ICP, CPP), CBF and arterial jugular differences in oxygen, glucose and lactate contents were measured for calculation of CMRO₂, CMRGlc and CMRLct. Results. Following hyperventilation, CBF was significantly reduced (P < 0.0001). CBF remained most often above the ischemic range although values less than 30 ml·100 gr⁻¹·min⁻¹ were found in 27.8% of patients. CBF reduction was associated with concurrent decrease in CMRO₂, anaerobic hyperglycolysis and subsequent lactate production. In contrast, mannitol resulted in significant albeit moderate improvement of cerebral perfusion. However, administration of mannitol had no ostensible effect either on oxidative or glucose metabolism and lactate balance remained mostly unaffected. Conclusions. Moderate hyperventilation may exacerbate pre-existing impairment of cerebral blood flow and metabolism in TBI patients and should be therefore carefully used under appropriate monitoring. Our findings rather support the use of mannitol for ICP control.     

Effects of iso- and hypervolemic hemodilution on regional cerebral blood flow and oxygen delivery for patients with vasospasm after aneurysmal subarachnoid hemorrhage

Summary. Summary.   Background: Arterial vasospasm after subarachnoid hemorrhage may cause cerebral ischemia. Treatment with hemodilution, reducing blood viscosity, and hypervolemia, increasing cardiac performance and distending the vasospastic artery, are clinically established methods to improve blood flow through the vasospastic arterial bed.   Method: Eight patients with transcranial Doppler verified vasospasm after subarachnoid hemorrhage were investigated with global (two-dimensional ¹³³Xenon) and regional (three-dimensional ^{99 m}Tc-HMPAO) cerebral blood flow (CBF) measurements, before and after 1/iso- and 2/hypervolemic hemodilution. Hematocrit was reduced to 0.28 from 0.36. Hypervolemia was achieved by increasing blood volume by 1100 ml.   Findings: Isovolemic hemodilution increased global cerebral blood flow from 52.25±10.12 to 58.56±11.73 ml * 100 g⁻¹ * min⁻¹ (p<0.05), but after hypervolemic hemodilution CBF returned to 51.38±11.34 ml * 100 g⁻¹ * min⁻¹. Global cerebral delivery rate of oxygen (CDRO₂) decreased from 7.94±1.92 to 6.98±1.66 ml * 100 g⁻¹ * min⁻¹ (p<0.001) during isovolemic hemodilution and remained reduced, 6.77±1.60 ml * 100 g⁻¹ * min⁻¹ (p<0.001), after the hypervolemic hemodilution. As a test of the hemodilution effect on regional CDRO₂ an ischemic threshold was defined as the maximal amount of oxygen transported by a CBF of 10 ml * 100 g⁻¹ * min⁻¹ at a Hb 140 g/l which corresponds to a CDRO₂ of 1.83 ml * 100 g⁻¹ * min⁻¹. The brain volume with a CDRO₂ exceeding the ichemic threshold was 1300±236 ml before intervention. After isovolemic hemodilution the non-ischemic brain volume was reduced to 1206±341 (p<0,003). After hypervolemic hemodilution the non-ischemic brain volume remained reduced at 1228±347 ml (p<0.05).   Interpretation: The present study of controlled isovolemic hemodilution demonstrated increased global CBF, but there was a pronounced reduction in oxygen delivery capacity. Both CBF and CDRO₂ remained decreased during further hypervolemic hemodilution. We conclude that hemodilution to hematocrit 0.28 is not beneficial for patients with cerebral vasospasm after SAH. Published online July 18, 2002     

Effect of Oxygen Affinity of Liposome‐Encapsulated Hemoglobin on Cerebral Ischemia and Reperfusion as Detected by Positron Emission Tomography in Nonhuman Primates

We tested a hypothesis that liposome‐encapsulated hemoglobin (LEH) with high oxygen (O₂) affinity (h‐LEH, P₅₀O₂ = 10 mm Hg) may work better than LEH with low O₂ affinity (l‐LEH, P₅₀O₂ = 40 mm Hg) in cerebral ischemia and reperfusion injury using positron emission tomography (PET) in primates undergoing middle cerebral artery (MCA) occlusion and reperfusion. Cerebral blood flow (CBF), O₂ extract fraction (OEF), and cerebral metabolic rate of O₂ (CMRO₂) were successively determined by PET before ischemia, at 2 h of ischemia, immediately after reperfusion, and 3 h after reperfusion. Five minutes after MCA occlusion, 10 mL/kg of h‐LEH (n = 6) was intravenously infused and compared with the results from previous data of monkeys treated with l‐LEH (n = 6), empty liposome (n = 4), or saline (n = 8) as control. After the series of PET studies, the integrated area of cerebral infarction was determined histologically in 12 coronal brain slices. There was no significant difference in CBF, OEF, or CMRO₂ up to 2 h of ischemia. A high CBF with a low OEF tended to be suppressed after reperfusion in LEH‐treated monkeys. Three hours after reperfusion, the area of mild CMRO₂ reduction (down to ?30%) decreased (P < 0.05) and the area of mild CMRO₂ increase (up to 30%) expanded in LEH‐treated monkeys (P < 0.05) regardless of O₂ affinity with no difference in the area of moderate‐to‐severe reduction (2 compared to animals treated with empty liposome or saline. Distribution of CMRO₂ reduction and histological damages showed that LEH mainly protected the cerebral cortex rather than basal ganglia where neuronal dendritic processes were severely lost. There was little difference between the animals treated with l‐LEH or h‐LEH both at 10 mL/kg or between treatment with empty liposome or saline. In conclusion, LEH was effective regardless of O₂ affinity in preserving CMRO₂ and in reducing the area of histological damage in the cerebral cortex, but not in basal ganglia, shortly after occlusion/reperfusion of MCA in monkey.     

Time-related changes in the cerebral blood flow in subarachnoid hemorrhage due to ruptured cerebral aneurysm]

Cerebral blood flow (CBF) was determined by the 123I-IMP SPECT reference sample method in 39 patients with subarachnoid hemorrhage (SAH) due to ruptured cerebral aneurysm. They were examined according to the time lapse after onset, severity, CT findings, and prognosis. These 39 patients were admitted to our medical center within 36 hours after the onset, and SAH and ruptured aneurysm were diagnosed by CT scan and angiography, respectively. Patients with intraventricular hemorrhage, intracerebral hematoma, and other severe complications were excluded. The stage of SAH was divided into three, by designating the day of onset as day 0: day 0-4 as the acute stage, day 5-20 as the subacute stage, and day 21 and after that as the chronic stage. Acute stage surgery was conducted within 48 hours after the onset on principle. Hyperdynamic therapy and cisternal drainage were conducted in severe case of SAH. The prognosis was evaluated with Glasgow outcome scale (GOS). The average CBF was 33.39, 29.44, and 33.15 in the acute, subacute, and chronic stages, respectively. These are values lower than the reference sample value, 43.39 (ml/100 g/min). Only a small number of cases, however, revealed vasospasm by angiography conducted in the acute stage. There was a correlation between the CT severity in the acute stage and the decrease in CBF. In the group with low density area (LDA) on CT due to delayed cerebral ischemia in the subacute stage, the average CBF was 28.28 and 23.95 in the acute and subacute stages, respectively. These values were significantly lower than 35.97 and 32.45, respectively, in the group without LDA.(ABSTRACT TRUNCATED AT 250 WORDS)     

The acute effect of nimodipine on cerebral blood flow,its CO2 reactivity,and cerebral oxygen metabolism in human volunteers

Summary The present study was undertaken in 8 healthy volunteers to examine the effect of a clinically relevant dose of nimodipine (NIM) (15 and 30 microgram/kg/h) on CBF, its CO₂ reactivity, and CMRO₂. Mean arterial blood pressure (MABP) was measured intra-arterially. Regional CBF was measured by SPECT of inhaled Xenon-133. During the CO₂ reactivity tests changes in CBF were estimated by the arterio-venous-oxygen-difference method. Median CBF was 52 ml/ 100 g/min (48–53) with a normal regional distribution, and median baseline MABP was 96 mmHg (92–99). MABP was slightly reduced, by 8 mmHg (7–9), and 9 mmHg (4–11) after infusion of NIM for 2 and 4 hours, respectively. CBF, however, remained constant, although correction for changes in PaCO₂, revealed a slight increase after 4 hours (p=0.08). CMRO2 was 3.5 ml/100 g/min (3.2–3.5) and was not changed by the infusion of NIM. At arterial CO₂ tensions ranging from 4.0 to 6.5 Kpa the CO₂ reactivity was 3.0% CBF/ 0.1 kPa (2.6–3.7) and decreased significantly to 2.6% CBF/0.1 kPa (1.8–3.2) after the infusion of NIM for 3 hours (p=0.02). The median slope of the LnCBFsat/PaCO₂ relationship was 1.5 at baseline compared to 1.3 after NIM (p<0.01). No side effects were observed.The present study shows a decreased CO₂ of the cerebral vessels and a maintained coupling of CBF and CMRO₂ during the infusion of nimodipine.     

Haemodynamic and metabolic changes following extra-intracranial bypass surgery

Summary In order to study the haemodynamic and metabolic changes following bypass surgery, the regional cerebral blood flow (rCBF), the oxygen extraction fraction (rOEF), the cerebral metabolic rate of oxygen (rCMRO₂), and the cerebral blood volume (rCBV) were measured using a positron emission tomograph (PET) on 13 patients who had unilateral internal carotid artery and/or middle cerebral artery occlusion. The patients were divided into two subgroups according to pre-operative rOEF values from the arterial occlusion side: the misery perfusion group, which had high rOEF values (0.56), and the coupling perfusion group, which had normal rOEF values (0.38–0.48). A post-operative PET study was performed 1–2 months and/or 1–5 years following the surgery. Six of the misery perfusion cases showed a post-operative CBF increase, where an accompanying OEF decreased to its normal level, indicating an attenuated misery perfusion state. The CMRO₂ values, however, remained low. The other 7 coupling perfusion cases had an ipsilateral CBF increase in the earlier PET study. We conclude that misery perfusion is attenuated following bypass surgery, although the procedure does not consistently improve oxygen metabolism.     

Evaluation of therapeutically induced hypertension in patients with delayed cerebral vasospasm by xenon-enhanced computed tomography.

Serial cerebral blood flow (CBF) measurements were made with stable xenon-enhanced computed tomography in 20 patients with angiographically confirmed ruptured intracranial aneurysms, before and during induced hypertension with continuous infusion of dopamine. All patients showed angiographic vasospasm during their course. Twelve patients without symptomatic vasospasm (Group 1) had the lowest hemispheric CBF on the craniotomy side of 31.6 +/- 6.8 ml/100 gm/min on days 4-9 (control value, 40.1 +/- 2.0 ml/100 gm/min), while the other eight patients with symptomatic vasospasm (Group 2) had the lowest hemispheric CBF on the craniotomy side of 25.0 +/- 7.6 ml/100 gm/min on days 10-14. The critical hemispheric CBF inducing neurological deficits was about 20 ml/100 gm/min in Group 2. Dysautoregulation was usually present in Groups 1 and 2, but therapeutically induced hypertension could reverse the delayed neurological deficits, if begun early at the stage of delayed vasospasm.     

Superoxide dismutase activity in cisternal cerebrospinal fluid after aneurysmal subarachnoid haemorrhage

Summary It has been recognised that the level of superoxide dismutase (SOD) significantly increases in CSF as the result of cerebral ischaemic damage. The aim of this study was to correlate the CSF levels of SOD enzymatic activity to the patterns of subarachnoid haemorrhage with regards to ischaemic complications due to vasospasm.A series of 78 patients operated on for intracranial aneurysms was studied; all patients were monitored with serial TCD measurements every second day after SAH. CSF samples were obtained at surgery by cisternal puncture of the subarachnoid cistern nearest to the aneurysm. SOD activity was assayed spectrophotometrically.Mean cisternal CSF level of SOD in 12 control cases (12.99±2.33 U/ml) is significantly higher (p < 0.01) than in 26 patients operated on between day 1 and 3 from last SAH episode (4.44±0.7 U/ml) and in 40 patients treated by delayed surgery (7.64±0.92 U/ml). In 13 patients presenting neurological deterioration related to arterial vasospasm mean cisternal SOD level was 12.23±1.86 U/ml; in 27 cases without vasospasm mean level was 5.43±0.7 U/ml (p < 001).The present results suggest that (a) cisternal CSF levels of SOD significantly decreases after SAH, probably in relation to an impaired synthesis in the brain compartment and that (b) a substantial elevation of SOD levels is evident in patients suffering ischaemic complications vasospasm-related. Biochemical events in the brain compartment could influence the expression and release of anti-oxidant enzymes in CSF after SAH.     

Magnetic resonance imaging in experimental subarachnoid haemorrhage

Summary Background. We developed an MRI protocol to measure cerebrovascular diameter and blood flow velocity, and if we could detect cerebrovascular alterations after SAH and their impact on cerebral ischaemia.Method. SAH was induced in 15 Wistar rats by means of the endovascular filament method; 6 other rats served as control. MRI measurements were performed on a 4.7T NMR spectrometer 1 and 48 hours after SAH and 9 days thereafter. Diffusion-weighted and T₂-weighted images were acquired to detect cerebral ischaemia. The arterial spin labelling method was used to measure CBF. MR angiography was used to measure vessel diameter and blood flow velocity, from which the arterial blood flow was calculated.Findings. The ischemic lesion volume increased between 1 and 48 hours after SAH from 0.039 to 0.26 ml (P = 0.003). CBF decreased from 53.6 to 39.1 ml/100 g/min. The vessel diameter had narrowed, the blood flow velocity diminished as did the arterial blood flow in most vessels, but only the vasoconstriction in the right proximal ICA reached significance (0.49 mm to 0.43 mm, P = 0.016). Baseline values were restored at day 9.Conclusions. We showed that it is feasible to detect alterations of in-vivo vessel diameter and blood flow velocities and their consequences for brain damage after experimental SAH in the rat. The growth of the infarct volume between day 0 and 2 after SAH and the parallel vasoconstriction suggest that delayed cerebral ischaemia after SAH occurs in rats and that this may be caused by vasoconstriction.     

Measurements of CO2 reactivity and barbiturate reactivity in patients with severe head injury

Summary In nine patients with severe head injury subjected to continuous hyperventilation and barbiturate coma treatment with pentobarbitone, the regional cerebral blood flow was measured as initial slope index (ISI) with a 32 channel Cerebrograph, and cerebral metabolic rate of oxygen (CMRO₂) was calculated as the product of mean global CBF and the arterio-venous oxygen content difference.CBF was measured at strategic intervals either to follow the treatment (hyperventilation and/or pentobarbitone), or to determine whether these principles of treatment should be intensified or reduced. During the flow measurements the CO₂ reactivity and the reactivity to a bolus injection of thiopentone 5 mg/kg were calculated globally and regionally. The global CO₂ reactivity was calculated as relative (%change CBF/PaCO₂ mmHg) and absolute (CBF/ PaCO₂ mmHg), and the reactivity to barbiturate was calculated globally as CMRO₂, and regionally as %change rCBF.The absolute and relative global CO₂ reactivities correlated positively with the mean. CBF values before hyperventilation, and the global barbiturate reactivity was dependent on the CMRO₂ value obtained before hyperventilation. However, at low levels of CMRO₂ ranging between 1.0 and 1.1 ml O₂ the barbiturate reactivity was abolished. The regional studies of CBF, CMRO₂, CO₂ reactivity and barbiturate reactivity gave important information, when decisions concerning therapeutic regimes with special reference to hyperventilation and sedation with pentobarbitone were necessary.