Increase In Cerebral Metabolic Rate Research Articles

Changes in volumetric and metabolic parameters relate to differences in exposure to sub-concussive head impacts

Structural and calibrated magnetic resonance imaging data were acquired on 44 collegiate football players prior to the season (PRE), following the first four weeks in-season (PTC) and one month after the last game (POST). Exposure data collected from g-Force accelerometers mounted to the helmet of each player were used to split participants into HIGH (N = 22) and LOW (N = 22) exposure groups, based on the frequency of impacts sustained by each athlete. Significant decreases in grey-matter volume specific to the HIGH group were documented at POST (P = 0.009), compared to baseline. Changes in resting cerebral blood flow (CBF0), corrected for partial volume effects, were observed within the HIGH group, throughout the season (P < 0.0001), suggesting that alterations in perfusion may follow exposure to sub-concussive collisions. Co-localized significant increases in cerebral metabolic rate of oxygen consumption (CMRO2|0) mid-season were also documented in the HIGH group, with respect to both PRE- and POST values. No physiological changes were observed in the LOW group. Therefore, cerebral metabolic demand may be elevated in players with greater exposure to head impacts. These results provide novel insight into the effects of sub-concussive collisions on brain structure and cerebrovascular physiology and emphasize the importance of multi-modal imaging for a complete characterization of cerebral health.

Acute hypoxia increases the cerebral metabolic rate – a magnetic resonance imaging study

The aim of the present study was to examine changes in cerebral metabolism by magnetic resonance imaging of healthy subjects during inhalation of 10% O2 hypoxic air. Hypoxic exposure elevates cerebral perfusion, but its effect on energy metabolism has been less investigated. Magnetic resonance imaging techniques were used to measure global cerebral blood flow and the venous oxygen saturation in the sagittal sinus. Global cerebral metabolic rate of oxygen was quantified from cerebral blood flow and arteriovenous oxygen saturation difference. Concentrations of lactate, glutamate, N-acetylaspartate, creatine and phosphocreatine were measured in the visual cortex by magnetic resonance spectroscopy. Twenty-three young healthy males were scanned for 60 min during normoxia, followed by 40 min of breathing hypoxic air. Inhalation of hypoxic air resulted in an increase in cerebral blood flow of 15.5% (p = 0.058), and an increase in cerebral metabolic rate of oxygen of 8.5% (p = 0.035). Cerebral lactate concentration increased by 180.3% (), glutamate increased by 4.7% () and creatine and phosphocreatine decreased by 15.2% (p). The N-acetylaspartate concentration was unchanged (p = 0.36). In conclusion, acute hypoxia in healthy subjects increased perfusion and metabolic rate, which could represent an increase in neuronal activity. We conclude that marked changes in brain homeostasis occur in the healthy human brain during exposure to acute hypoxia.

Catecholamine depletion in first-degree relatives of individuals with mood disorders: An [18F]fluorodeoxyglucose positron emission tomography study

Catecholamine depletion with alpha-methylparatyrosine (AMPT) has previously been shown to induce depressive symptoms in currently remitted patients with major depressive disorder (MDD) but not healthy controls. Thus sensitivity to catecholamine depletion has been hypothesized to be an endophenotype of MDD. Here we tested this hypothesis in the context of a randomized, double-blinded, placebo-controlled design by measuring changes in mood in a group of psychiatrically-healthy individuals at risk of mood disorders by virtue of family history (high-risk subjects, HRs). In addition, we tested whether HRs differed from healthy controls with no family-history of mood disorders (low-risk controls, LRs) in their cerebral metabolic response when undergoing catecholamine depletion. Eight healthy LRs (6 males, mean age = 34.1 ± 7.1) and 6 healthy HRs (3 males, mean age = 29.3 ± 4.6) participated in two, 3-day-long identical sessions during which they completed standardized measures of depression, anxiety and fatigue and an [18F]fluorodeoxyglucose (FDG) positron emission tomography (PET) scan. On one occasion participants received 4 weight-adjusted doses of AMPT and on the other occasion participants received 4 doses of placebo. The LR and HR groups did not differ from each other in their mood during sham depletion. However, during the period of peak catecholamine depletion, the HR group reported significantly more depression, anxiety and fatigue than the LR group. A region-of-interest analysis showed that during catecholamine depletion versus placebo the combined LR and HR groups displayed a significant increase in cerebral metabolic rate in the left and right ventral striata, left and right amygdalae, and left and right hippocampi (FWE-corrected p < 0.05). Whole brain voxel-wise analyses indicated significantly increased glucose metabolism in the left and right putamina (FWE-corrected p < 0.05) in the combined LR and HR groups in the AMPT versus the placebo session. In the LR group, alone, no significant elevation in glucose metabolism was observed in the regions-of-interest in the catecholamine depletion versus placebo condition. In the HR group, alone, the region-of-interest analysis showed a significant increase in cerebral metabolic rate in the left and right ventral striata (FWE-corrected p < 0.05). No regions-of-interest showed significantly different metabolism in the HR group versus the LR group in the placebo condition, however compared with the LR group, the HR group displayed nominally increased glucose metabolism in the left amygdala during catecholamine depletion (SVC-corrected p = 0.05). A region-of-interest analysis for the interaction contrast confirmed that catecholamine depletion had differential effects on HR and LR participants. Compared with the LR group, the HR group displayed significantly increased glucose metabolism in the left ventral striatum, left amygdala, and left lateral orbitofrontal cortex (OFC) (FWE-corrected p < 0.05). Our results suggest that sensitivity to catecholamine depletion may be a phenotypic marker of vulnerability to mood disorders that is characterized at the neurophysiological level by disinhibition of the striatum and its efferent projections comprising the limbic–cortical–striatal–pallidal–thalamic circuitry.

Chapter 15. Analgesics, sedatives, and neuromuscular blockade

Chapter 15. Analgesics, sedatives, and neuromuscular blockade

Cerebral glucose and lactate consumption during cerebral activation by physical activity in humans

At rest, the brain takes up oxygen and carbohydrate at an ~6:1 ratio. Exercise increases systemic lactate availability reducing this to as little as 1.7:1 despite a ~20% increase in cerebral metabolic rate for oxygen (CMRo₂), thus indicating a disproportionate increase of carbohydrate metabolism. Underlining mechanisms and metabolic fate for the augmented lactate uptake are unknown. This meta-analysis examines whether adrenergic activation explains the increased lactate uptake, cerebral lactate release following cerebral activation compensates for the extra carbohydrate uptake during exercise, and cerebral lactate uptake spares glucose as fuel. Ten studies (n=96) measuring arteriovenous differences for lactate, glucose, and oxygen and cerebral blood flow were included. Cerebral lactate uptake increased during brain activation by whole-body exercise compared to the resting state. Unlike glucose, lactate uptake is proportional to its arterial concentration but is unaffected by sympathetic activity. Following exercise, significant cerebral lactate released as arterial lactate levels decreased, which may balance the surplus lactate uptake in the brain during physical activity in the long term. Finally, cerebral glucose uptake was reduced by ~25% in relation to CMRo₂ when cerebral lactate uptake increased, suggesting, in part, preferential lactate consumption during activation. This meta-analysis favors the notion that cerebral lactate uptake is mainly passively governed by its availability, but when lactate is available, lactate supplements glucose and supports an increase in cerebral energy metabolism in an activity-dependent manner.

Functional neuroimaging: a physiological perspective

Metabolic physiology and functional neuroimaging have played important and complementary roles over the past two decades. In particular, investigations of the mechanisms underlying functional neuroimaging signals have produced fundamental new insights into hemodynamic and metabolic regulation. However, controversies were also raised as regards the metabolic pathways (oxidative vs. non-oxidative) for meeting the energy demand and driving the increases in cerebral blood flow (CBF) during brain activation. In a recent study, with the concurrent functional MRI-MRS measurements, we found that task-evoked energy demand was predominately met through oxidative metabolism (approximately 98%), despite a small increase in cerebral metabolic rate of oxygen (12–17%). In addition, the task-induced increases in CBF were most likely mediated by anaerobic glycolysis rather than oxygen demand. These observations and others from functional neuroimaging support the activation-induced neuron-astrocyte interactions portrayed by the astrocyte-neuron lactate shuttle model. The concurrent developments of neuroimaging methods and metabolic physiology will also pave the way for the future investigation of cerebral hemodynamics and metabolism in disease states.

Dynamics and nonlinearities of the BOLD response at very short stimulus durations

In designing a functional imaging experiment or analyzing data, it is typically assumed that task duration and hemodynamic response are linearly related to each other. However, numerous human and animal studies have previously reported a deviation from linearity for short stimulus durations (<4 s). Here, we investigated nonlinearities of blood-oxygenation-level-dependent (BOLD) signals following visual stimulation of 5 to 1000 ms duration at two different luminance levels in human subjects. It was found that (a) a BOLD response to stimulus durations as short as 5 ms can be reliably detected; this stimulus duration is shorter than employed in any previous study investigating BOLD signal time courses; (b) the responses are more nonlinear than in any other previous study: the BOLD response to 1000 ms stimulation is only twice as large as the BOLD response to 5 ms stimulation although 200 times more photons were projected onto the retina; (c) the degree of nonlinearity depends on stimulus intensity; that is, nonlinearities have to be characterized not only by stimulus duration but also by stimulus features like luminance. These findings are especially of most practical importance in rapid event-related functional magnetic resonance imaging (fMRI) experimental designs. In addition, an 'initial dip' response--thought to be generated by a rapid increase in cerebral metabolic rate of oxygen metabolism (CMRO2) relative to cerebral blood flow--was observed and shown to colocalize well with the positive BOLD response. Highly intense stimulation, better tolerated by human subjects for short stimulus durations, causes early CMRO2 increase, and thus, the experimental design utilized in this study is better for detecting the initial dip than standard fMRI designs. These results and those from other groups suggest that short stimulation combined with appropriate experimental designs allows neuronal events and interactions to be examined by BOLD signal analysis, despite its slow evolution.

Effect of hyperoxia on regional oxygenation and metabolism after severe traumatic brain injury: Preliminary findings*

To determine the effect of normobaric hyperoxia on cerebral metabolism in patients with severe traumatic brain injury. Prospective clinical investigation. Neurosciences critical care unit of a university hospital. Eleven patients with severe traumatic brain injury. Cerebral microdialysis, brain tissue oximetry (PbO2), and oxygen-15 positron emission tomography (15O-PET) were undertaken at normoxia and repeated at hyperoxia (FiO2 increase of between 0.35 and 0.50). Established models were used to image cerebral blood flow, blood volume, oxygen metabolism, and oxygen extraction fraction. Physiology was characterized in a focal region of interest (surrounding the microdialysis catheter) and correlated with microdialysis and oximetry. Physiology was also characterized in a global region of interest (including the whole brain), and a physiologic region of interest (defined using a critical cerebral metabolic rate of oxygen threshold). Hyperoxia increased mean +/- sd PbO2 from 28 +/- 21 mm Hg to 57 +/- 47 mm Hg (p = .015). Microdialysate lactate and pyruvate were unchanged, but the lactate/pyruvate ratio showed a statistically significant reduction across the study population (34.1 +/- 9.5 vs. 32.5 +/- 9.0, p = .018). However, the magnitude of reduction was small, and its clinical significance doubtful. The focal region of interest and global 15O-PET variables were unchanged. "At-risk" tissue defined by the physiologic region of interest, however, showed a universal increase in cerebral metabolic rate of oxygen from a median (interquartile range) of 23 (22-25) micromol x 100 mL(-1) x min(-1) to 30 (28-36) micromol x 100 mL(-1) x min(-1) (p < .01). In severe traumatic brain injury, hyperoxia increases PbO2 with a variable effect on lactate and lactate/pyruvate ratio. Microdialysis does not, however, predict the universal increases in cerebral metabolic rate of oxygen in at-risk tissue, which imply preferential metabolic benefit with hyperoxia.

Changes in regional cerebral metabolism during systemic hyperthermia in humans.

Whole body hyperthermia may produce vasodialation, nausea, and altered cognitive function. Animal research has identified brain regions that have important roles in thermoregulation. However, differences in both the cognitive and sweating abilities of humans and animals implicate the need for human research. Positron emission tomography (PET) was used to identify brain regions with altered activity during systemic hyperthermia. Human subjects were studied under cool (control) conditions and during steady-state hyperthermia induced by means of a liquid-conditioned suit perfused with hot water. PET images were obtained by injecting [(18)F]fluorodeoxyglucose, waiting 20 min for brain uptake, and then scanning for 10 min. Heating was associated with a 23% increase in resting metabolic rate. Significant increases in cerebral metabolic rate occurred in the hypothalamus, thalamus, corpus callosum, cingulate gyrus, and cerebellum. In contrast, significant decreases occurred in the caudate, putamen, insula, and posterior cingulum. These results are important for understanding the mechanisms responsible for altered cognitive and systemic responses during hyperthermia. Novel regions (e.g., lateral cerebellum) with possible thermoregulatory roles were identified.

The Influence of Inhaled Nitric Oxide on Cerebral Blood Flow and Metabolism in a Child with Traumatic Brain Injury

The Influence of Inhaled Nitric Oxide on Cerebral Blood Flow and Metabolism in a Child with Traumatic Brain Injury

Positron emission tomography and fluorodeoxyglucose studies of metabolic hyperfrontality and psychopathology in the psilocybin model of psychosis.

The effects of the indolehallucinogen psilocybin, a mixed 5-HT2 and 5-HT1 agonist, on regional cerebral glucose metabolism were investigated in 10 healthy volunteers with PET and [F-18]-fluorodeoxyglucose (FDG) prior to and following a 15- or 20-mg dose of psilocybin. Psychotomimetic doses of psilocybin were found to produce a global increase in cerebral metabolic rate of glucose (CMRglu) with significant and most marked increases in the frontomedial and frontolateral cortex (24.3%), anterior cingulate (24.9%), and temporomedial cortex (25.3%). Somewhat smaller increases of CMRglu were found in the basal ganglia (18.5%), and the smallest increases were found in the sensorimotor (14.7%) and occipital cortex (14.4%). The increases of CMRglu in the prefrontal cortex, anterior cingulate, temporomedial cortex, and putamen correlated positively with psychotic symptom formation, in particular with hallucinatory ego disintegration. The present data suggest that excessive 5-HT2 receptor activation results in a hyperfrontal metablic pattern that parallels comparable metabolic findings associated with acute psychotic episodes in chronic schizophrenics and contrasts with the hypofrontality in chronic schizophrenic patients.

Effects of propranolol pretreatment on cerebral blood flow, oxygen uptake and catecholamines during metabolic acidosis following E. coli endotoxin in dogs.

After an intravenous injection of E. coli endotoxin in dogs a decrease in cerebral blood flow (CBF) and an increase in cerebral metabolic rate of oxygen (CMRo2) have been shown to occur. In metabolic acidosis following endotoxin CMRo2 increased with decreasing pH. A possible explanation for the increased CMRo2 after endotoxin and metabolic acidosis seems to be a damage of the blood-brain barrier (BBB) by endotoxin. This gives possibilities for a leakage of hydrogen ions and circulating monoamines from the blood to the brain, thus affecting the cerebral blood flow and metabolism. The effects of an E. coli endotoxin injection on CBF and CMRo2 during metabolic acidosis and beta-adrenoceptor blockade were studied in eight anaesthetized dogs. All the dogs were pretreated with propranolol (PPL), per os 12.5 mg.kg-1 twice a day for one week. Metabolic acidosis (pH 7.01-7.30) was achieved by an intravenous infusion of hydrochloric acid. Endotoxin E. coli lipopolysaccharide O 111:B 4 was given as an intravenous injection of 1 mg.kg-1 bodyweight over a 5 min period. Another five animals, published earlier, with the same experimental protocol but without PPL, constituted a control group. After endotoxin no increase in CMRo2 or CBF was observed with increasing acidosis in the PPL-group. In the control group, after endotoxin, both CBF and CMRo2 increased with decreasing pH. This resulted in a significant difference in both CBF and CMRo2 between the groups in the pH range 7.01-7.15. The present results indicate that the increase in CMRo2 and CBF with metabolic acidodis in endotoxinaemia is mediated via beta-adrenoceptors.

Effects of arterial hypoxia and β‐adrenoceptor blockade on cerebral blood flow and oxygen uptake following E. coli endotoxin in dogs

Earlier studies in normoxia have shown that an endotoxin injection in dogs leads to an increase in cerebral metabolic rate of oxygen (CMRo2), a decrease in cerebral blood flow (CBF) and increased concentrations of monoamines in blood and cerebrospinal fluid (CSF). In animals pretreated with propranolol (PPL) the CMRo2 increase was abolished and thus beta-adrenoceptor mediated. Arterial hypoxia normally increases CBF without any influence on CMRo2. The aim of this study was to investigate the effects of moderate arterial hypoxia on CBF, CMRo2 and catecholamine concentrations in blood and CSF after endotoxin with and without pretreatment with PPL. Three groups of dogs were studied. Group 1: Six animals were subjected to arterial hypoxia without any other intervention. Group 2: Six animals were given an endotoxin injection (E. coli lipopolysaccharide O 111: B 4), before the induction of hypoxia. Group 3: Eight animals were pretreated with PPL per os, 12.5 mg.kg-1 twice a day for one week before the experiments, and the effects of arterial hypoxia were studied both before and after an intravenous injection of endotoxin. Two levels of hypoxia were studied; oxygen saturation in arterial blood aiming at 75 and 50%. Endotoxin was given intravenously in a dose of 1 mg.kg-1 bodyweight over a 5 minute period. After an endotoxin injection, the response to arterial hypoxia was an increase in CMRo2, in contrast to the unchanged CMRo2 without endotoxin. After pretreatment with PPL the increase in CMRo2 after endotoxin was prevented. The CBF reaction to hypoxia was uniformly an increase.(ABSTRACT TRUNCATED AT 250 WORDS)

Nitrous Oxide Increases Cerebral Blood Flow Velocity During Pharmacologically Induced EEG Silence in Humans

We examined the effect of nitrous oxide on cerebral blood flow velocity (Vmca), arteriovenous oxygen content difference and cerebral use of glucose during propofol-induced electrical silence of the electroencephalogram (EEG) in 10 patients undergoing anesthesia for nonneurosurgical procedures. Anesthesia was induced with propofol 2.5 mg/kg, fentanyl 3 micrograms/kg (followed by an infusion of 2 micrograms/kg/h), vecuronium 0.1 mg/kg, and maintained with a propofol infusion (250-300 micrograms/kg/min) sufficient to induce EEG silence. A transcranial Doppler was used to measure the Vmca and a jugular bulb catheter was inserted for oxygen saturation and glucose use measurements. After a 15-period of isoelectric EEG and normocapnia (PaCO2 38 +/- 1 mm Hg), baseline arterial and jugular bulb venous blood gases were drawn, and mean arterial pressure (MAP), heart rate (HR), and Vmca were recorded. Nitrous oxide was then introduced and equilibrated to an end-tidal concentration of 70% for 15 min, after which MAP, HR, Vmca, arterial and jugular bulb venous blood gases were measured again. Nitrous oxide increased Vmca (29 +/- 4 to 35 +/- 4 cm/s, p < 0.01), cerebral use of oxygen (166 +/- 13 to 190 +/- 12 vol%-cm/s, p < 0.05) and glucose (245 +/- 38 to 290 +/- 48 g%-cm/s, p < 0.05) by approximately 20%. Occasional bursts of EEG activity were observed in eight patients studied during the N2O stage. We conclude that in patients with propofol-induced isoelectric EEG, the increase seen in Vmca with the introduction of N2O is mainly due to cerebral stimulation and increase in cerebral metabolic rate.

Cerebral blood flow and metabolism in fulminant liver failure

Fulminant liver failure is a syndrome that is frequently complicated by cerebral edema and increased intracranial pressure. Cerebral blood flow has been reported as high in some studies but low in others. This study undertook to measure cerebral blood flow and cerebral metabolic rate for oxygen in 30 patients with fulminant liver failure in grade 4 encephalopathy and to assess these parameters after intervention with hyperventilation and infusions of mannitol, epoprostenol and acetylcysteine. Cerebral blood flow varied widely, from 14 to 71 ml/100 gm/min (normal range, 41 to 66), whereas the cerebral metabolic rate for oxygen was low in all patients, 0.16 to 2.03 ml/100 gm/min (normal range, 3.12 to 3.96). Twenty-one of the 30 patients had evidence of anaerobic metabolism with cerebral lactate production. Hyperventilation resulted in a significant decrease in both cerebral blood flow (median, 36 to 28 ml/100 gm/min) and cerebral metabolic rate for oxygen (median, 0.92 to 0.65 ml/100 gm/min); mannitol and acetylcysteine infusions resulted in significant increases in both of these parameters. Prostaglandin I2 infusion did not significantly alter cerebral blood flow, but there was a significant increase in cerebral metabolic rate for oxygen. The depressed cerebral metabolic rate for oxygen in patients with fulminant liver failure is inappropriate to metabolic requirements, as demonstrated by both cerebral lactate production and the increase in cerebral oxygen consumption after improvement in cerebral blood flow. Mannitol infusion should remain the main treatment of the cerebral complications of fulminant liver failure. Acetylcysteine has a beneficial effect that is not restricted to fulminant liver failure after acetaminophen overdose and has a role in the management of patients, regardless of cause of illness. The use of prostaglandin I2 appears to be safe and may be beneficial. Acute hyperventilation causes decreases in both cerebral blood flow and cerebral metabolic rate for oxygen and has the potential to worsen cerebral ischemia. (HEPATOLOGY 1994;19:1407–1413.)

Cerebral blood flow and metabolism in fulminant liver failure

Fulminant liver failure is a syndrome that is frequently complicated by cerebral edema and increased intracranial pressure. Cerebral blood flow has been reported as high in some studies but low in others. This study undertook to measure cerebral blood flow and cerebral metabolic rate for oxygen in 30 patients with fulminant liver failure in grade 4 encephalopathy and to assess these parameters after intervention with hyperventilation and infusions of mannitol, epoprostenol and acetylcysteine. Cerebral blood flow varied widely, from 14 to 71 ml/100 gm/min (normal range, widely, from 14 to 71 ml/100 gm/min (normal range, 41 to 66), whereas the cerebral metabolic rate for oxygen was low in all patients, 0.16 to 2.03 ml/100 gm/min (normal range, 3.12 to 3.96). Twenty-one of the 30 patients had evidence of anaerobic metabolism with cerebral lactate production. Hyperventilation resulted in a significant decrease in both cerebral blood flow (median, 36 to 28 ml/100 gm/min) and cerebral metabolic rate for oxygen (median, 0.92 to 0.65 ml/100 gm/min); mannitol and acetylcysteine infusions resulted in significant increases in both of these parameters. Prostaglandin I2 infusion did not significantly after cerebral blood flow, but there was a significant increase in cerebral metabolic rate for oxygen. The depressed cerebral metabolic rate for oxygen in patients with fulminant liver failure is inappropriate to metabolic requirements, as demonstrated by both cerebral lactate production and the increase in cerebral oxygen consumption after improvement in cerebral blood flow. Mannitol infusion should remain the main treatment of the cerebral complications of fulminant liver failure.(ABSTRACT TRUNCATED AT 250 WORDS)

Pathophysiological mechanisms of brain damage from status epilepticus.

Human status epilepticus (SE) is consistently associated with cognitive problems, and with widespread neuronal necrosis in hippocampus and other brain regions. In animal models, convulsive SE causes extensive neuronal necrosis. Nonconvulsive SE in adult animals also leads to widespread neuronal necrosis in vulnerable regions, although lesions develop more slowly than they would in the presence of convulsions or anoxia. In very young rats, nonconvulsive normoxic SE spares hippocampal pyramidal cells, but other types of neurons may not show the same resistance, and inhibition of brain growth, DNA and protein synthesis, and of myelin formation and of synaptogenesis may lead to altered brain development. Lesions induced by SE may be epileptogenic by leading to misdirected regeneration. In SE, glutamate, aspartate, and acetylcholine play major roles as excitatory neurotransmitters, and GABA is the dominant inhibitory neurotransmitter. GABA metabolism in substantia nigra (SN) plays a key role in seizure arrest. When seizures stop, a major increase in GABA synthesis is seen in SN postictally. GABA synthesis in SN may fail in SE. Extrasynaptic factors may also play an important role in seizure spread and in maintaining SE. Glial immaturity, increased electronic coupling, and SN immaturity facilitate SE development in the immature brain. Major increases in cerebral blood flow (CBF) protect the brain in early SE, but CBF falls in late SE as blood pressure falters. At the same time, large increases in cerebral metabolic rate for glucose and oxygen continue throughout SE. Adenosine triphosphate (ATP) depletion and lactate accumulation are associated with hypermetabolic neuronal necrosis. Excitotoxic mechanisms mediated by both N-methyl-D-aspartate (NMDA) and non-NMDA glutamate receptors open ionic channels permeable to calcium and play a major role in neuronal injury from SE. Hypoxia, systemic lactic acidosis, CO2 narcosis, hyperkalemia, hypoglycemia, shock, cardiac arrhythmias, pulmonary edema, acute renal tubular necrosis, high output failure, aspiration pneumonia, hyperpyrexia, blood leukocytosis and CSF pleocytosis are common and potentially serious complications of SE. Our improved understanding of the pathophysiology of brain damage in SE should lead to further improvement in treatment and outcome.

Effects of Nitrous Oxide on Cerebral Metabolic Rate in Rats Anaesthetized with Isoflurane

It has been demonstrated in several species that a significant increase in cerebral blood flow (CBF) occurs when nitrous oxide is added to a volatile anaesthetic. This blood flow response could result from an increase in cerebral metabolic rate or from a direct effect of nitrous oxide on cerebral vessels. To investigate this, the cerebral metabolic rate for glucose (CMRglu) was determined autoradiographically in rats receiving isoflurane anaesthesia with or without nitrous oxide. An increase in anaesthetic depth from 0.5 to 1.0 MAC achieved with isoflurane alone caused a significant reduction in CMRglu (52 (SD11) μmol/100 gmin −1 vs 39 (8) μmol/100 g min −1 ). In contrast, the addition of 70% nitrous oxide (0.5 MAC) to 0.5 MAC isoflurane anaesthesia (1 MAC total) left CMRglu unchanged (54 (4) μmol/100 g min −1 ). We conclude that 70% nitrous oxide does not alter cerebral metabolic rate when administered with 0.5 MAC isoflurane. Because CBF increases substantially under very similar conditions, our data indicate that the CBF effects of nitrous oxide, when administered with a volatile agent, were direct and mediated by factors other than changes in cerebral metabolic rate.

EFFECTS OF NITROUS OXIDE ON CEREBRAL METABOLIC RATE IN RATS ANAESTHETIZED WITH ISOFLURANE

It has been demonstrated in several species that a significant increase in cerebral blood flow (CBF) occurs when nitrous oxide is added to a volatile anaesthetic. This blood flow response could result from an increase in cerebral metabolic rate or from a direct effect of nitrous oxide on cerebral vessels. To investigate this, the cerebral metabolic rate for glucose (CMRglu) was determined autoradiographically in rats receiving isoflurane anaesthesia with or without nitrous oxide. An increase in anaesthetic depth from 0.5 to 1.0 MAC achieved with isoflurane alone caused a significant reduction in CMRglu (52 (SD11) mumol/100 g min-1 vs 39 (8)mumol/100 g min-1). In contrast, the addition of 70% nitrous oxide (0.5 MAC) to 0.5 MAC isoflurane anaesthesia (1 MAC total) left CMRglu unchanged (54 (4) mumol/100 g min-1). We conclude that 70% nitrous oxide does not alter cerebral metabolic rate when administered with 0.5 MAC isoflurane. Because CBF increases substantially under very similar conditions, our data indicate that the CBF effects of nitrous oxide, when administered with a volatile agent, were direct and mediated by factors other than changes in cerebral metabolic rate.

Cerebral hemodynamics, oxygen uptake and cerebral arteriovenous differences of catecholamines following E. coli endotoxin in dogs.

In experimental endotoxic shock in dogs, a decrease in cerebral blood flow and an increase in cerebral metabolic rate of oxygen (CMRO2) have been shown to occur. In this situation the blood levels of adrenaline and noradrenaline are markedly elevated. The aim of the present study was to investigate whether a cerebral uptake of circulating catecholamines with a possible influence on CMRO2 takes place in the brain. In eight anaesthetized dogs, arterial blood, superior sagittal sinus blood and cerebrospinal fluid were analyzed for the concentrations of adrenaline, noradrenaline and dopamine before and up to 4 h after an injection of E. coli endotoxin 1.0-1.5 mg . kg-1. The blood levels of adrenaline and noradrenaline, but not dopamine, increased in response to the endotoxin. From about 30 min after the endotoxin injection, arteriovenous adrenaline and noradrenaline differences indicating a cerebral uptake were most often seen. Increased concentrations of noradrenaline, adrenaline and dopamine in cerebrospinal fluid were observed. Noradrenaline gave the highest concentrations and these were correlated to the CMRO2. In some animals the blood and cerebrospinal fluid concentrations of adrenaline seemed to be related. These results indicate that catecholamines might be of importance for the development of an increased CMRO2 in endotoxic shock.