Cerebral blood flow and metabolism during adenosine–induced hypotension in patients undergoing cerebral aneurysm surgery

The effects of adenosine-induced hypotension on cerebral blood flow (CBF), cerebral metabolic rate of oxygen (CMRO2), and cerebral lactate production, together with systemic haemodynamics, were studied in 10 patients undergoing cerebral aneurysm surgery in neurolept anaesthesia with controlled hyperventilation. CBF changes were determined in six of the patients with a retrograde thermodilution technique in the jugular vein. Hypotension was induced with a continuous infusion of adenosine in the superior vena cava. The dose range was 0.06-0.35 mg/kg/min, and this caused a 42% reduction in mean arterial blood pressure (MABP) from 79 +/- 4 to 46 +/- 1 mmHg (10.5 +/- 0.5 to 6.1 +/- 0.1 kPa) through a profound reduction in systemic vascular resistance (SVR), which amounted to 61%. No significant change occurred in CBF. Whole body AV-difference of oxygen was decreased by 37%, and cerebral AV-difference by 28%, corresponding to reductions in whole body oxygen uptake and CMRO2 of 16 and 17%, respectively. Cerebral AV-difference of lactate did not change. In the posthypotensive period MABP was increased by 10%, together with a minor increase in CBF (15%). It is concluded, that adenosine-induced hypotension at MABP levels between 40-50 mmHg (5.3-6.7 kPa) does not affect cerebral oxygenation unfavourably, and may even offer a protective effect by reducing cerebral oxygen demand. The slight CBF increase in the posthypotensive period was probably secondary to an increase in MABP together with a blunted autoregulation, but in no case was this effect considered to be harmful for the patient.     

Cerebral blood flow and glucose metabolism in the squirrel monkey during the late phase of cerebral vasospasm

Summary A double-isotope autoradiography technique was used to evaluate cerebral blood flow (CBF) and cerebral glucose metabolism (CMRglu) during the late phase of vasospasm in a squirrel monkey subarachnoid haemorrhage (SAH) model. Cisternal blood injections induced both global and focal changes in CBF and CMRglu six days following SAH, the timepoint of maximal late spasm in this model. There was a global decrease in CBF of about 30% accompanied by an increase in deoxyglucose uptake of about 50%. Four of seven animals also had foci with flow decreased to 40% of control and deoxyglucose uptake increased to 300% of control. There was an altered but still present interdependence between flow and metabolism post SAH.     

Combined effects of propofol and mild hypothermia on cerebral metabolism and blood flow in rhesus monkey: a positron emission tomography study

Purpose Propofol reduces the cerebral metabolic rate for oxygen (CMRO₂), regional CMRO₂ (rCMRO₂), cerebral blood flow (CBF), and regional CBF (rCBF), but maintains the coupling of cerebral metabolism and blood flow. Under mild to moderate hypothermia, the coupling is maintained, while rCBF is reduced, but no direct measurement of rCMRO₂ has yet been reported. This study aimed to evaluate the effects of propofol under normothermic and mild hypothermic temperatures upon rCMRO₂, rCBF, and their regional coupling, through direct measurement by positron emission tomography. Methods Rhesus monkeys were anesthetized with 65% nitrous oxide and propofol. Then rCBF and rCMRO₂ were measured under four sets of conditions: infusion of a low-propofol dose (12 mg·kg⁻¹·h⁻¹) at normothermic temperatures (38°C), a high dose (25 mg·kg⁻¹·h⁻¹) at normothermic temperatures, a low dose under mild hypothermia (35°C), and a high dose under mild hypothermia. The ratio of rCBF/rCMRO₂ was calculated from these data. Results Reductions in CMRO₂ and rCMRO₂ in most regions were associated with two factors: the higher propofol dose and the induction of hypothermia, but there was no interaction between these factors. Concerning blood flow, no significant reduction was observed, except for CBF by the induction of hypothermia. The ratio of rCBF/rCMRO₂ was constant in this study setting. Conclusion During propofol anesthesia, it is possible to reduce cerebral metabolism throughout the entire brain as well as in any brain region by increasing the propofol dose or inducing hypothermia. The concurrent use of these two interventions has an additive effect on metabolism, and can be considered as safe, as their combination does not impair the coupling of cerebral metabolism and blood flow.     

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.     

Sequential changes in cerebral blood flow and metabolism in patients with subarachnoid haemorrhage

Summary Haemodynamic and metabolic sequences were investigated in nine patients having subarachnoid haemorrhage (SAH) up to 3 months following aneurysmal rupture, using positron emission tomography (PET). In the pre-spasm stage (2–4 days after SAH) cerebral blood flow (CBF, ml/100 ml/min) was 45±11, the cerebral metabolic rate of oxygen (CMRO₂, ml/100 ml/min) was 2.68±0.50, and cerebral blood volume (CBV, ml/100 ml) was 5.5±1.2. CBF within the normal range and a relatively low CMRO₂, indicated relative hyperaemia. This was possibly due to the direct toxic effect of SAH on the brain metabolism. CBV was considerably elevated. The spasm stage (6–15 days after SAH) showed CBF values of 39±7, CMRO₂ values of 2.42±0.50, and CBV values of 5.4±1.7. CBF decreased significantly (p<0.05 vs pre-spasm stage), and CMRO₂ also tended to decrease, while they were coupling. It is likely that this may have been induced by vasospasm. Thereafter, the PET parameters normalized gradually. During all the stages studied, significant laterality of the PET parameters was not observed. This may be because SAH and vasospasm provide diffuse pathophysiological conditions for the entire brain and cerebral arteries.     

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.     

Cerebral arteriovenous difference of oxygen during gradual and sudden increase of the concentration of isoflurane for induction of deliberate hypotension

In 20 patients undergoing surgery for cerebral aneurysms, hypotension was induced with either gradual (over 5 min) or sudden increase of inspiratory concentration of isoflurane from 0.5% to 3%. Both modes elicited the same speed of induction of deliberate hypotension and similar decreases of cerebral arteriovenous difference of oxygen (AVDo2). The overall median values of mean arterial blood pressure decreased from 75.5 (range 64-90) mmHg (10 (8.5-12.0) kPa) to 55 (40-66) mmHg (7.3 (5.3-8.8) kPa) and the overall AVDo2 decreased from 6.75 ml/100 ml (3.8-9.4 ml/100 ml) to 5.85 ml/100 ml (2.6-8.1 ml/100 ml) within 10 min. It is concluded that irrespective of gradual or sudden increase of isoflurane concentration, cerebral blood flow is in surplus of metabolism and a favourable oxygen demand/supply ratio is maintained during induction of deliberate hypotension by isoflurane below 2.5 MAC.     

Cerebral blood flow,computerized tomography and angiography in 562 cases of cerebrovascular insufficiency

The measurement of cerebral blood flow (CBF) in addition to cerebral computerized tomography (CT) and angiography is most reliable in cases of transient ischemic attacks (TLA) and prolonged reversible ischemic neurologic deficits (PRIND). Alterations of CBF can be detected in symptom-free intervals. The cerebrovascular reactivity to CO₂ stimulus is regarded as an especially suitable tool to prove the cerebrovascular reserve. If it is diminished, cerebral angiography should be carried out since it will often show major obstructive lesions.Angiography shows no sure correlation between CBF and collateral circulation. Strong opthalmic pathways in unilateral occlusion of the internal carotid artery (ICA) often coincide with compensated or only slightly alterated CBF and relatively small infarcts in CT.In about 70% of cases of ICA occlusion, CT shows an infarct mostly in region of the middle cerebral artery (MCA). Largest infarct volumes were found in the anterior area. Although resting CBF was normal in 55% of cases of unilateral ICA occlusion, CO₂ reactivity was impaired in 68% of these Cases.     

Cerebral vasoreactivity and the prediction of outcome in severe traumatic brain lesions

Mean hemispheric blood flow (CBF) was studied in 38 comatose, severely brain-injured patients following intravenous administration of xenon-133. Repeated measurements were performed in order to evaluate cerebral vasoreactivity following a decrease in PaCO2. Simultaneously, arterial-venous oxygen differences (AVDO2) and intracranial pressure (ICP) were measured. An impaired CBF response to hyperventilation (delta CBF/delta PaCO2 less than 1.0) was obtained in 22 patients. Three of 16 patients with preserved CO2-reactivity died because of their brain injuries and 12 patients reached good recovery/moderate disability. In the group of patients with impaired vasoreactivity 11 of 22 patients died and only three patients reached good recovery/moderate disability. The study documents that in patients with severe traumatic brain lesions measurements of cerebral vasoreactivity to hyperventilation give prognostic information that is not obtained by clinical observations or CT-scanning.     

Brain energy metabolism and blood flow during sevoflurane and halo thane anesthesia: effects of hypocapnia and blood pressure fluctuations

The effects of halothane and sevoflurane on cat brain energy metabolism and regional cerebral blood How (rCBF) were evaluated during normo- and hypocapnia. Brain energy status was evaluated with phosphorous nuclear magnetic resonance spectroscopy (³¹P-MRS) and rCBF was measured by the hydrogen clearance method. A high concentration of halothane (3 MAC) impaired brain energy metabolism, while even a higher concentration of sevoflurane (4 MAC) had no untoward effect on brain energy metabolism. At 3 MAC of halothane, there were measurable decreases in brain phosphocreatine (69% of the control) and increases in brain inorganic phosphate (about 250% of control Pi), even though CBF was about 70% of the control value. During hypocapnia, the phosphocreatine levels began to decrease at a Paco₂ of 2.7 kPa with 2 MAC of sevoflurane (90% of the control), and at a Paco₂ of 4.0 kPa with 2 MAC of halothane (92% of the control). rCBF had decreased to less than 50%) of the control value when Paco₂ was ≤2.7 kPa with 2 MAC of sevoflurane and ≤4.0 kPa with 2 MAC of halothane. Abnormal brian energy metabolism was only observed when rCBF was decreased to less than half of the control (non-anesthetized and normocapnie) value. Following administration of a vasopressor, metaraminol, the abnormal brain energy metabolism induced by 2 MAC of halothane at a Paco₂ of 1.33 kPa was normalized in parallel with the improved rCBF values. We conclude that hyperventilation and fluctuating blood pressure contribute to the occurrence of abnormal brain energy metabolism during halothane and sevoflurane anesthesia. This is more pronounced with halothane than with sevoflurane. The hypocapnia-induced abnormality during exposure to 2 MAC of either agent was due to decreased CBF associated with low perfusion pressure, indicating that there was no direct effect of these anesthetics on cerebral energy metabolism.     

Cerebral glucose and energy metabolism,cerebral oxygen consumption,and blood flow in arterial hypoxaemia

Summary The influence of moderately reduced arterial oxygen tension (aPO₂ of about 45 Torr) on the metabolism and the blood flow of the brain was tested in 20 anaesthetized, artificially ventilated normotensive, normocapnic beagle dogs. It is demonstrated that the decrease in systemic oxygen delivery to the brain is countered by an appropriate increase in flow (CBF being 60.3 ml/100 g min at normoxia and 84.5 mg/100 g min m hypoxaemia) which maintained the cerebral oxygen consumption unchanged (CMRO₂ 3.80 versus 3.32 ml/100 g min). The cortical tissue content of energy-rich phosphates such as ATP, ADP, AMP, and phosphocreatine was also found to be unaltered. Neuropathological examinations excluded any hypoxic cell damage. This reactive vasodilatory reaction of the cerebral vessels is apparently a sensitive regulatory process which protects the brain against marked oxygen lack. However, a normal carbohydrate metabolism is not restored by this cerebrovascular mechanism. For, significantly increased CMRlactate (0.32 versus 1.46 ml/100 g min) indicated raised cerebral glycolysis, and the tissue metabolites of glucose suggested an increased glycolytic flux in the brain. It is concluded that in moderate arterial hypoxaemia, which is not uncommon in clinical practice, cerebral blood flow plays an effective homeostatic role in preventing a disturbance of the energy metabolism of the brain.     

Effects of adenosine–induced hypotension on cerebral blood flow and metabolism in the pig

The cerebral and systemic effects of hypotension induced by adenosine (0.61 +/- 0.07 mg.kg-1.min-1) were studied in eight pigs anesthetized with droperidol, phenoperidine and nitrous oxide. Mean arterial blood pressure (MABP) was reduced by 58%, from 17.2 kPa (128 mmHg) to 6.9 kPa (53 mmHg) during a 30-min period. The hypotension was caused by a decrease in systemic vascular resistance (58%) while the cardiac output was unaffected. Cerebral blood flow (CBF), as determined by microsphere distribution, and the cerebral metabolic rate for oxygen (CMRO2) remained unchanged. Cerebral vascular resistance decreased by 61%. There were no signs of cerebral lactate release. After discontinuation of adenosine infusion, the MABP returned to control levels within 5 min. Thirty minutes later the CBF was increased by approximately 60% in comparison to the control, while the CMRO2 was unchanged. It is concluded that adenosine-induced hypotension in pigs is associated with preserved CBF and CMRO2, whereas cerebral hyperperfusion is present in the early post-hypotensive period.     

No influence of the endothelin receptor antagonist bosentan on basal and indomethacin-induced reduction of cerebral blood flow in pigs

BACKGROUND: The mechanism behind indomethacin-induced cerebral vasoconstriction is incompletely understood. We tested the hypothesis that the mixed endothelin-1 receptor antagonist bosentan would modify or prevent indomethacin-induced reduction of CBF in the anaesthetized pig. Furthermore, we investigated the effect of bosentan on resting CBF and CMRO2. METHODS: Twelve pigs were randomized in two groups of six, and received either bosentan and indomethacin (group 1), or placebo and indomethacin (group 2). Anaesthesia was induced with ketamine and midazolam and maintained with fentanyl, nitrous oxide and pancuronium. Baseline measurements of CBF and CMRO2 were performed before intravenous bolus injection of bosentan (10 mg/kg) or placebo (0.9% NaCl). The second CBF and CMRO2 measurement was performed 30 min after administration of bosentan/placebo. A 40-min infusion of indomethacin (0.05 mg/kg/min) was administered and the third CBF and CMRO2 measurement was performed 80 min after administration of bosentan/placebo. Independently, pharmacokinetic data of bosentan were generated in four pigs. RESULTS: In group 1, baseline CBF was 55 +/- 7 ml/100 cm3/min. Administration of bosentan i.v. did not change CBF significantly. Indomethacin decreased CBF to 41 +/- 5 ml/100 cm3/min (P < 0.002). In group 2, baseline CBF was 54 +/- 10 ml/100 cm3/min. Placebo did not change CBF while indomethacin decreased CBF significantly to 41 +/- 5 ml/100 cm3/min (P < 0.002). No significant changes in CMRO2 were observed. In group 2, a significant increase in MABP was observed after administration of indomethacin. No change in MABP was observed in the bosentan-treated animals. Total plasma concentrations of bosentan at the time of the first and the second PET measurement were 3.9 and 1.4 microg/ml, respectively. The corresponding values for the pharmacologically active metabolite Ro 48-5033 were 1.2 and 0.4 microg/ml. CONCLUSION: These findings indicate that endothelin receptor stimulation is not involved in indomethacin-induced cerebral vasoconstriction or maintenance of cerebrovascular tone in the anaesthetized pig. However, our results suggest that the increase in MABP is mediated through endothelin receptors.     

Ketamine, Not Propofol, Attenuates Cerebrovascular Response to Carbon Dioxide in Humans With Isoflurane Anesthesia

Study Objectives: To investigate the effects of ketamine and propofol on the cerebrovascular response to carbon dioxide (CO₂) in humans during isoflurane anesthesia.

Design: Randomized clinical investigation.

Settings: University hospital of a medical school.

Patients: 30 ASA physical status I and II adult, elective surgical patients.

Interventions and Measurements: With each patient given air/oxygen/isoflurane anesthesia, the flow velocity in the middle cerebral artery (Vmca) and pulsatility index were measured using the transcranial Doppler method under hypocapnic [arterial CO₂tension (Pa ₂) 28–32 mmHg], normocapnic (Pa ₂ 38–42 mmHg), and hypercapnic conditions (Pa ₂ 48–52 mmHg). Pa ₂ was altered by supplementing the inspired gas with CO₂ without changing the respiratory conditions. Patients were then randomly assigned to receive either ketamine 1 mg · kg⁻¹ or propofol (2 mg · kg⁻¹followed by an infusion of 6–10 mg · kg⁻¹ · hr⁻¹) (n = 15 for each drug), and the measurements were repeated.

Main Results: Ketamine reduced both absolute and relative cerebrovascular reactivity to CO₂ significantly [2.9 ± 0.8 (control) vs. 2.6 ± 1.0 (ketamine) cm · sec⁻¹ · mmHg⁻¹: p < 0.05; and 3.5 ± 0.7 (control) vs. 2.8 ± 0.9 (ketamine) % · mmHg⁻¹: p < 0.01, respectively]. However, ketamine did not reduce Vmca during hypercapnic conditions (117 ± 29 cm · sec⁻¹) compared with controls (120 ± 28 cm · sec⁻¹). Although propofol decreased Vmca during all conditions, it did not cause any change in either absolute or relative CO₂ reactivity [2.5 ± 0.8 (control) vs. 2.5 ± 1.0 (propofol) cm · sec⁻¹ · mmHg⁻¹, and 3.3 ± 1.3 (control) vs. 4.1 ± 1.0 (propofol) % · mmHg⁻¹, respectively].

Conclusions: In humans given isoflurane anesthesia, a) ketamine reduced cerebrovascular response to CO₂, but cerebral blood flow (CBF) during hypercapnic conditions was comparable with controls, and b) although propofol decreases CBF, it maintains the cerebrovascular response to CO₂.     

CBF and CMRo2 during craniotomy for small supratentorial cerebral tumours in enflurane anaesthesia. A dose-response study

In 14 patients with supratentorial cerebral tumours with midline shift less than or equal to 10 mm, cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO2) were measured twice on the contralateral side of the craniotomy, using a modification of the Kety & Schmidt method. For induction of anaesthesia, thiopental, fentanyl and pancuronium were used. The anaesthesia was maintained with enflurane 1% in nitrous oxide 67%. Moderate hypocapnia to a level averaging 4.3 kPa was achieved. The patients were divided into two groups. In Group 1 (n = 7), 1% enflurane was used throughout the anaesthesia, and CBF and CMRO2 measured about 70 min after induction averaged 30.1 ml 100 g-1 min-1 and 1.98 ml O2 100 g-1 min-1, respectively. During the second CBF study 1 h later, CBF and CMRO2 were unchanged (P greater than 0.05). In Group 2 (n = 7), the inspiratory enflurane concentration was increased from 1 to 2% after the first CBF measurement. In this group a significant decrease in CMRO2 was observed, while CBF was unchanged. In six patients EEG was recorded simultaneously with the CBF measurements. In patients subjected to increasing enflurane concentration (Group 2), a suppression in the EEG activity was observed without spike waves. It is concluded that enflurane induces a dose-related decrease in CMRO2 and suppression in the EEG activity, whereas CBF was unchanged.     

Cerebral blood flow and oxygen consumption during isoflurane and halothane anesthesia in man

In 13 patients, the effects on cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO2) of isoflurane and halothane administered in a clinically relevant situation were studied. Measurements were performed during fentanyl/nitrous oxide (65%) anesthesia together with moderate hyperventilation (PaCO2 approx 4.5 kPa), and repeated after addition of 0.65 MAC of isoflurane (n = 6) or halothane (n = 7). CBF was measured after intravenous administration of 133xenon and CMRO2 was calculated from the arterial venous differences of oxygen content (AVDO2) determined in arterial and jugular venous bulb blood. CBF and CMRO2 (means +/- s.e. mean) determined prior to administration of volatile agents were 28 +/- 5 ml x 100(-1) x min-1 and 2.0 +/- 0.3 ml x 100 g-1 x min-1, respectively, in the isoflurane group. In the halothane group, CBF was 25 +/- 0.4 ml x 100 g-1 x min-1 and CMRO2 was 2.0 +/- 0.4 ml x 100 g-1 x ml-1. There were no significant intergroup differences. Isoflurane did not change CBF, whereas halothane produced an increase of 36% (P less than 0.05) compared to values obtained during fentanyl/N2O anesthesia. In addition, isoflurane caused a further decrease in CMRO2 of 12% (P less than 0.01) as compared to a 20% increase (P less than 0.05) with halothane. The cerebral metabolic depression caused by the short-acting anesthetic induction agents would be expected to decrease with time, and could partly explain the observed increase in CMRO2 produced by halothane. The study suggests that the cerebrovascular and metabolic properties of isoflurane differ from those of halothane, also in man.     

Cerebral blood flow, cerebral metabolic rate of oxygen and relative CO2-reactivity during craniotomy for supratentorial cerebral tumours in halothane anaesthesia. A dose-response study

Fourteen patients were studied during craniotomy for small supratentorial cerebral tumours. Cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO2) were measured twice by a modification of the Kety-Schmidt technique using 133Xe intravenously. Anaesthesia was induced with thiopental 4-6 mg kg-1, fentanyl and pancuronium, and maintained with an inspiratory halothane concentration of 0.45% in nitrous oxide 67% at a moderate hypocapnic level. In one group of patients (n = 7) the inspiratory halothane concentration was maintained at 0.45% throughout anaesthesia. About 1 h after induction of anaesthesia CBF and CMRO2 averaged 35 +/- 2 ml 100 g-1 min-1 and 2.7 +/- 0.3 ml O2 100 g-1 min-1 (mean +/- s.c. mean), respectively. During repeat studies 1 h later CBF and CMRO2 did not change. In another group of patients (n = 7) an increase in halothane concentration from 0.45% to 0.90% was associated with a significant decrease in CMRO2 from 2.3 +/- 0.1 to 2.0 +/- 0.1 ml O2 100 g-1 min-1. The CO2-reactivity measured after the second flow measurement was preserved. It is concluded that halothane in this study induces a dose-dependent decrease in cerebral metabolism, an increase in CBF while CO2-reactivity is maintained.     

CBF and CMRO2 during Continuous Etomidate Infusion Supplemented with N2O and Fentanyl in Patients with Supratentorial Cerebral Tumour. A Dose-Response Study

In 14 patients with supratentorial cerebral tumours with midline shift below 10 mm, CBF and CMRO2 were measured (Kety & Schmidt) during craniotomy. The anaesthesia was continuous etomidate infusion supplemented with nitrous oxide and fentanyl. The patients were divided into two groups. In Group 1 etomidate infusion of 30 micrograms kg-1 min-1 was used throughout the anaesthesia, and CBF and CMRO2 were measured twice. In this group CMRO2 (means +/- s.d.) averaged 2.31 +/- 0.43 ml O2 100 g-1 min-1 70 min after induction and 2.21 +/- 0.38 ml O2 100 g-1 min-1 130 min after induction. In Group 2 the etomidate infusion was increased from 30 to 60 micrograms kg-1 min-1 after the first study and a significant fall in CMRO2 from 2.52 +/- 0.56 to 1.76 +/- 0.40 ml O2 100 g-1 min-1 was found. Simultaneously, a significant fall in CBF was observed. The CO2 reactivity was preserved during anaesthesia.     

The sequential change of local cerebral blood flow and local cerebral glucose metabolism after focal cerebral ischaemia and reperfusion in rat and the effect of MK-801 on local cerebral glucose metabolism

Summary In order to investigate the time course change of local cerebral blood flow (1CBF) and local cerebral glucose metabolism (1CGM) and the effect of MK-801 (dizocilpine), an NMDA receptor antagonist on glucose metabolism in a middle cerebral artery occlusion-reperfusion model,¹⁴C-Iodo-antipyrine and¹⁴C-Deoxyglucose autoradiographic method have been used. The 1CBF was reduced to 0–10% of the control level in the ischaemic core and to 12–40% in the ischaemic penumbra between 60 and 120 min after the onset of the ischaemia. In the ischaemic core, the marked hyperfusion appeared at 15 min and maintained about 30 to 45 min following reperfusion. In the ischaemic penumbra, the hyperfusion during reperfusion was not found. Hypermetabolism occurred at 30 min and reached to the peak at 60 min after the middle cerebral artery (MCA) occlusion both in the ischaemic core and in the penumbra. The shift from hyper- to hypometabolism was observed during the ischaemia. The reperfusion following 2 hours of MCA occlusion facilitated the decrease of cerebral glucose metabolism in the ischaemic region. The pretreatment of MK-801 (0.4 mg/kg) inhibited both increased glucose metabolism during the ischaemia and decreased glucose metabolism during the reperfusion. The effect of limiting decreased glucose metabolism during the reperfusion by MK-801 was remarkable in the ischaemic penumbra. These findings support the hypothesis that excitation-induced hypermetabolism play a major role in the ischaemic insult following focal cerebral vascular occlusion.