Regional cerebral blood flow during hyperventilation in patients with acute bacterial meningitis.

Mechanical hyperventilation is often instituted in patients with acute bacterial meningitis when increased intracranial pressure is suspected. However, the effect on regional cerebral blood flow (CBF) is unknown. In this study, we measured regional CBF (rCBF) in patients with acute bacterial meningitis before and during short-term hyperventilation. In 17 patients with acute bacterial meningitis, absolute rCBF (in ml/100 g min-1) was measured during baseline ventilation and hyperventilation by single-photon emission computed tomography (SPECT) using intravenous 133Xe bolus injection. Intravenous 99mTc-HMPAO (hexamethylpropyleneamine oxime) was subsequently given during hyperventilation. In 12 healthy volunteers, rCBF was measured by SPECT and 99mTc-HMPAO during spontaneous ventilation. Using standard templates to identify regions of interest (ROIs), we calculated rCBF in percentage of cerebellar (99mTc-HMPAO images) or mean hemispheric (133Xe images) flow for each ROI, the degree of side-to-side asymmetry for each ROI, and the anterior-to-posterior flow ratio. On 133Xe images, absolute rCBF decreased significantly during hyperventilation compared to baseline ventilation in all regions, but the relative rCBF did not change significantly from baseline ventilation (n=14) to hyperventilation (n=12), indicating that the perfusion distribution was unchanged. On 99mTc-HMPAO images (n=12), relative rCBF and the anterior-to-posterior flow ratio were significantly lower in patients than in controls in the frontal and parietal cortex as well as in the basal ganglia. Focal perfusion abnormalities were present in 10 of 12 patients. Regional cerebral blood flow abnormalities are frequent in patients with acute bacterial meningitis. Short-term hyperventilation does not enhance these abnormalities.     

Fulminant hepatic failure induced oxidative stress in nonsynaptic mitochondria of cerebral cortex in rats

Fulminant hepatic failure (FHF) is a condition with sudden onset of necrosis of hepatocytes and degeneration of liver tissue without any established liver disease. FHF is associated with increased ammonia levels in blood and brain, which is supposed to be neurotoxic, ultimately leading to neuronal death. Evidences from previous studies suggest for mitochondrial dysfunctions under hyperammonemic conditions. In the present investigation, on thioacetamide-induced FHF rat models, studies were undertaken on cerebral nonsynaptic mitochondrial oxidative stress. The results of the present study reveal elevated lipid peroxidation along with reduced total thiol levels in the cerebral cortex mitochondria of experimental animals compared to saline treated control rats. In addition, the enzymatic activities of glutathione peroxidase and glutathione reductase were decreased, with an elevation in Mn-SOD activity. Overall, thioacetamide-induced FHF in rats enhanced the levels of lipid peroxidation coupled with impaired antioxidant defenses in the cerebral nonsynaptic mitochondria.     

Effect of Cerebral Blood Flow and Cerebrovascular Autoregulation on the Distribution, Type and Extent of Cerebral Injury

Global cerebral blood flow (GCBF) is low in the human neonate compared to the adult. It is even lower in mechanically ventilated, preterm infants: 10-12 ml/100 g/minute, a level associated with brain infarction in adults. The reactivity, however, of global CBF to changes in cerebral metabolism, PaCO2, and arterial blood pressure is normal, except following severe birth asphyxia, or in mechanically ventilated preterm infants, who subsequently develop major germinal layer hemorrhage. The low level of cerebral blood flow (CBF) matches a low cerebral metabolism of glucose and a relatively small number of cortical synapses in the perinatal period. It has not been possible to define a threshold for GCBF below which electrical dysfunction or brain damage occurs (such as white matter and thalamic-basal ganglia necrosis). Three explanations for the lack of clear relation between GCBF and electrical brain activity of the preterm infant must be examined more closely: 1) low levels of CBF are adequate; 2) GCBF does not adequately reflect critically low perfusion of the white matter, and 3) acute white matter ischemia does not result in electrical silence. Two clinical patterns of brain damage following asphyxia may be explained by changes in the blood flow distribution induced by asphyxia: brainstem sparing and parasagittal cerebral injury. Hours to days after severe asphyxia, a state of marked global hyperperfusion may prevail. It is associated with poor neurological outcome and may be an entry point for trials of interventions aiming sat blocking the translation of asphyctic injury to cellular death and tissue damage.     

L-Ornithine phenylacetate (OP): a novel treatment for hyperammonemia and hepatic encephalopathy

Hepatic encephalopathy (HE) is a common neuropsychiatric complication of liver disease affecting about 20-30% patients with cirrhosis. HE may only affect quality of life (e.g. impairments in attention; coordination; driving ability), but in some patients this progresses to coma and death; defining mortality in those with acute liver failure. HE is thought to occur through accumulation of ammonia as a by-product of protein metabolism. In liver failure ammonia accumulates to toxic levels, resulting in ammonia-associated brain swelling. Presently, there is no proven therapy for HE though recent studies suggest that during liver failure, ammonia removal by skeletal muscle (by conversion to glutamine) can be manipulated; also that ammonia and amino acid metabolism should be viewed in terms of their interorgan relationship. This led us to develop a novel concept for ammonia removal. Preliminary studies provide the proof of concept that the combination of L-ornithine (amino acid) with phenylactetate, as L-ornithine phenylacetate (OP), reduces toxic levels of ammonia by (1) L-ornithine acting as a substrate for glutamine synthesis from ammonia in skeletal muscle and (2) phenylacetate excreting the ornithine-related glutamine as phenylacetylglutamine in the kidneys. As both L-ornithine and phenylacetate are already available for human use, data showing its usefulness in ammonia lowering could translate quickly into providing the much needed therapy for HE patients.     

Electrical impedance plethysmography: Its use in studying the cerebral circulation of the rabbit

Electrical impedance plethysmography (EIP) is a noninvasive method that may be useful for both the continuous and serial measurement of changes in pulsatile cerebral blood volume and perhaps cerebral blood flow (CBF). It has not been well validated by comparison with other methods. To attempt to validate the EIP technique, the relationship between the peak amplitude of the transcranial, cardiac-synchronous impedance waveform (dZ_p) and cerebral blood flow measured by the radiolabelled microsphere technique (CBF_rlm) and laser Doppler spectroscopy (CBF_rds) was studied in rabbits. CBF was altered by inducing hypertension using metaraminol, hypotension by controlled haemorrhage or hypocarbia by hyperventilation. Twenty-three comparisons between dZ_p and CBF_ids and 19 comparisons with CBF_rim were made in eight rabbits. The percentage change between each measurement using the three techniques in each animal was calculated. Using pooled data from all the animals, the linear regression equations were dZ_p=0.5 CBF_rim+33 (r=0.38, p=0.22, SE=79) and dZ_p=0.84 CBF_ids+19.6 (r=0.46, p=0.09, SE=72). It is concluded that, in the anaesthetised rabbit, when large changes in CBF are induced by the manoeuvres described above, changes in dZ_p correlate very weakly with changes in either cortical or global CBF, and are influenced by other factors such as pulsatile intracranial blood volume.     

Preventing and Treating Hypoxia: Using a Physiology Simulator to Demonstrate the Value of Pre-Oxygenation and the Futility of Hyperventilation

Introduction: Insufficient pre-oxygenation before emergency intubation, and hyperventilation after intubation are mistakes that are frequently observed in and outside the operating room, in clinical practice and in simulation exercises. Physiological parameters, as appearing on standard patient monitors, do not alert to the deleterious effects of low oxygen saturation on coronary perfusion, or that of low carbon dioxide concentrations on cerebral perfusion. We suggest the use of HumMod, a computer-based human physiology simulator, to demonstrate beneficial physiological responses to pre-oxygenation and the futility of excessive minute ventilation after intubation.Methods: We programmed HumMod, to A.) compare varying times (0-7 minutes) of pre-oxygenation on oxygen saturation (SpO₂) during subsequent apnoea; B.) simulate hyperventilation after apnoea. We compared the effect of different minute ventilation rates on SpO₂, acid-base status, cerebral perfusion and other haemodynamic parameters.Results: A.) With no pre-oxygenation, starting SpO₂ dropped from 98% to 90% in 52 seconds with apnoea. At the other extreme, following full pre-oxygenation with 100% O₂ for 3 minutes or more, the SpO₂ remained 100% for 7.75 minutes during apnoea, and dropped to 90% after another 75 seconds. B.) Hyperventilation, did not result in more rapid normalization of SpO₂, irrespective of the level of minute ventilation. However, hyperventilation did cause significant decreases in cerebral blood flow (CBF).Conclusions: HumMod accurately simulates the physiological responses compared to published human studies of pre-oxygenation and varying post intubation minute ventilations, and it can be used over wider ranges of parameters than available in human studies and therefore available in the literature.     

Relationship between cognitive function and regulation of cerebral blood flow

Ageing is the primary risk factor for cognitive deterioration. Given that the cerebral blood flow (CBF) or regulation of cerebral circulation is attenuated in the elderly, it could be expected that ageing-induced cognitive deterioration may be affected by a decrease in CBF as a result of brain ischemia and energy depletion. CBF regulation associated with cerebral metabolism thus likely plays an important role in the preservation of cognitive function. However, in some specific conditions (e.g. during exercise), change in CBF does not synchronize with that of cerebral metabolism. Our recent study demonstrated that cognitive function was more strongly affected by changes in cerebral metabolism than by changes in CBF during exercise. Therefore, it remains unclear how an alteration in CBF or its regulation affects cognitive function. In this review, I summarize current knowledge on previous investigations providing the possibility of an interaction between regulation of CBF or cerebral metabolism and cognitive function.     

Sympathetic influence on cerebral blood flow and metabolism during exercise in humans

This review focuses on the possibility that autonomic activity influences cerebral blood flow (CBF) and metabolism during exercise in humans. Apart from cerebral autoregulation, the arterial carbon dioxide tension, and neuronal activation, it may be that the autonomic nervous system influences CBF as evidenced by pharmacological manipulation of adrenergic and cholinergic receptors. Cholinergic blockade by glycopyrrolate blocks the exercise-induced increase in the transcranial Doppler determined mean flow velocity (MCA Vmean). Conversely, alpha-adrenergic activation increases that expression of cerebral perfusion and reduces the near-infrared determined cerebral oxygenation at rest, but not during exercise associated with an increased cerebral metabolic rate for oxygen (CMRO(2)), suggesting competition between CMRO(2) and sympathetic control of CBF. CMRO(2) does not change during even intense handgrip, but increases during cycling exercise. The increase in CMRO(2) is unaffected by beta-adrenergic blockade even though CBF is reduced suggesting that cerebral oxygenation becomes critical and a limited cerebral mitochondrial oxygen tension may induce fatigue. Also, sympathetic activity may drive cerebral non-oxidative carbohydrate uptake during exercise. Adrenaline appears to accelerate cerebral glycolysis through a beta2-adrenergic receptor mechanism since noradrenaline is without such an effect. In addition, the exercise-induced cerebral non-oxidative carbohydrate uptake is blocked by combined beta 1/2-adrenergic blockade, but not by beta1-adrenergic blockade. Furthermore, endurance training appears to lower the cerebral non-oxidative carbohydrate uptake and preserve cerebral oxygenation during submaximal exercise. This is possibly related to an attenuated catecholamine response. Finally, exercise promotes brain health as evidenced by increased release of brain-derived neurotrophic factor (BDNF) from the brain.     

Cerebral blood flow and metabolism during exercise

During exercise regional cerebral blood flow (rCBF), as blood velocity in major cerebral arteries and also blood flow in the internal carotid artery increase, suggesting an increase in blood flow to a large part of the brain. Such an increase in CBF is independent of the concomitant increase in blood pressure but is modified by the alteration in arterial carbon dioxide tension (PaCO(2)). Also, the increase in middle cerebral artery mean blood velocity (MCA V(mean)) reported with exercise appears to depend on the ability to increase cardiac output (CO), as demonstrated in response to beta-1 blockade and in patients with cardiac insufficiency or atrial fibrillation.Near-infrared spectroscopy (NIRS) determined cerebral oxygenation supports the alterations in MCA V(mean) during exercise. Equally, the observation that the cerebrovascular CO(2)-reactivity appears to be smaller in the standing than in the sitting and especially in the supine position could relate to the progressively smaller CO.In contrast, during exercise "global" cerebral blood flow (gCBF), as determined by the Kety-Schmidt technique is regarded as being constant. One limitation of the Kety-Schmidt method for measuring CBF is that blood flow in the two internal jugular veins depends on the origin of drainage and it has not been defined which internal jugular venous flow is evaluated. Such a consideration is equally relevant for an evaluation of cerebral metabolism during exercise.While the regional cerebral uptake of oxygen (O(2)) increases during exercise, the global value is regarded as being constant. Yet, during high intensity exercise lactate is taken up by the brain and its O(2) uptake also increases. Furthermore, in the initial minutes of recovery immediately following exercise, brain glucose and O(2) uptake are elevated and lactate uptake remains high.A maintained substrate uptake by the brain after exercise suggests a role for brain glycogen in cerebral activation, but the fate of brain substrate uptake has not yet been determined.     

Glutamine transport by mitochondria isolated from normal and acidotic rats.

The transport of L-glutamine by isolated rat renal mitochondria was studied by means of a rapid-filtration (Millipore Filter Corp.) technique. The movement of glutamine from the incubation medium into the inner mitochondrial compartment (matrix) was inhibited by structural analogues (6-diazo-5-oxo-L-norleucine and glutamic acid), sulghydryl-binding agents (p-chloromercuri-benzoate and mersalyl), and inhibitors of mitochondrial oxidative metabolism (azide, antimycin A, and uncouplers of oxidative phosphorylation). These results suggest that glutamine is transported across the inner membrane of renal mitochondria by a carrier-mediated system that is linked to the processes of oxidative metabolism. The transport of glutamine by isolated renal mitochondria was increased two- to threefold by chronic (5-7 days) metabolic acidosis. However, short-term metabolic acidosis did not increase the glutamine transport capacity of isolated mitochondria. A hypothesis is presented for the regulation of mitochondrial glutamine transport, in vivo, during short-term and chronic acidosis.     

Post traumatic brain perfusion SPECT analysis using reconstructed ROI maps of radioactive microsphere derived cerebral blood flow and statistical parametric mapping

Background  

Assessment of cerebral blood flow (CBF) by SPECT could be important in the management of patients with severe traumatic brain injury (TBI) because changes in regional CBF can affect outcome by promoting edema formation and intracranial pressure elevation (with cerebral hyperemia), or by causing secondary ischemic injury including post-traumatic stroke. The purpose of this study was to establish an improved method for evaluating regional CBF changes after TBI in piglets.     

Cerebral blood flow sensitivities to CO2 measured with steady-state and modified rebreathing methods

It is well established that the ventilatory response to carbon dioxide (CO(2)) measured by modified rebreathing (Sr(VE)) is closer to that measured by the steady-state method (Ss(VE)) than is the response measured by Read's rebreathing method. It is also known that the value estimated by the steady-state method depends upon the combination of data points used to measure it. The aim of this study was to investigate if these observations were also true for cerebral blood flow (CBF), as measured by steady-state (Ss(CBF)) and modified rebreathing (Sr(CBF)) tests. Six subjects undertook two protocols: (a) steady state: PET(CO2) was held at 1.5 mm Hg above normal (isocapnia) for 10 min, then raised to three levels of hypercapnia, (8 min each; 6.5, 11.5 and 16.5 mm Hg above normal, separated by 4 min isocapnia). End-tidal PO2 was held at 300 mm Hg; (b) modified rebreathing: subjects underwent 6 min of voluntary hyperventilation to PET(CO2) approximately 20 mm Hg, and then rebreathed via a 6l bag filled with 6.5% CO(2) in O(2). We confirmed that the value for Ss(VE) depended upon the combination of data points used to calculate it, and also confirmed that Ss(VE) and Sr(VE) were similar. However, this was not the case with CBF. Estimates of Ss(CBF) were the same, regardless of the data points used in calculation, and Ss(CBF) was 89% greater than Sr(CBF) (P<0.05). We interpret these findings as consistent with the notion that the specific CO(2) stimulus differs for CBF and ventilatory control. The data also indicate that prior hypocapnia in the modified rebreathing protocol may have a persistent effect on both cerebral vessels and central ventilatory control.     

Role of glial metabolism in diabetic encephalopathy as detected by high resolution 13C NMR

The roles of glial energetics and of the glutamine cycle in diabetic encephalopathy have been investigated ex vivo by (13)C NMR in extracts of adult rat brain. Streptozotocin-induced diabetic or euglycemic animals received intravenous infusions of (1-(13)C) glucose in the absence and presence of trifluoroacetic acid or methionine sulfoximine, two selective inhibitors of the glial tricarboxylic acid cycle or of glutamine synthase, respectively. (1-(13)C) glucose infusions resulted in smaller (13)C incorporation in all carbons of cerebral glutamate, glutamine and GABA in the diabetic animals. Co-infusion of trifluoroacetic acid with (1-(13)C) glucose further reduced the (13)C enrichments in cerebral glutamate and glutamine, the decrease being larger in the diabetic animals than in the corresponding euglycemic controls. Methionine sulfoximine decreased to undetectable levels the fractional (13)C enrichment in the carbons of cerebral glutamine in both groups and had no significant effect on (13)C incorporation in glutamate and GABA, suggesting that glutamine is not the main precursor of glutamate and GABA. Additional animals were infused with (1,2-(13)C(2)) acetate, a major substrate of glial metabolism. In this case, (1,2-(13)C(2)) acetate infusions resulted in increased (13)C incorporation in all carbons of glutamate, glutamine and GABA in the diabetic animals. Together, these results reveal that diabetic encephalopathy has an important effect in astroglial metabolism, decreasing glucose transport and metabolism and increasing the relative contribution of glial oxidative metabolism to the support of glutamatergic and GABAergic neurotransmissions.     

Approaches to editing, assignment and interpretation of proton spectra.

Clinical 1H spectroscopy of the brain is complemented by parallel analyses of biopsy specimens and by studies of animal models of disease. 1H spectroscopy has been carried out on perchloric acid extracts of biopsy specimens from patients with intracranial tumours. The data suggest that clinical spectroscopy may be useful in the identification and grading of these tumours. In addition, the spectra from extracts derived from normal white matter add weight to the possibility that acetyl-containing compounds other than N-acetylaspartate may make a significant contribution to the signal at 2.0 ppm in vivo. Edited 1H spectra of brain metabolites in rats with acute liver failure demonstrate an elevation of glutamine and of lactate, suggesting a role for 1H spectroscopy in clinical investigations of metabolic encephalopathies. However, the observation and resolution of signals from glutamate and glutamine is more difficult at the lower fields that are available for clinical spectroscopy. Finally, some studies of patients with inborn errors of metabolism are described. It is shown that in a disorder of oxidative metabolism, brain lactate can be detected without the need for complex spectral editing techniques. Investigations of the metabolic abnormalities associated with Canavan's disease have shed further light on a possible role for N-acetylaspartate.     

NH+4对星状胶质细胞谷氨酰胺代谢的影响

目的：了解体外培养状态下,ＮＨ４＋对脑星准确无误胶质细胞谷氨酰胺代谢的影响。方法;将不同浓度ＮＨ４ＣＩ加入培养液作用不同的时间,分别收集细胞及上清进行测定。结果：ＮＨ４＾＋作用后,星状胶质细胞谷氨酰胺合成酶活性啬细胞内及上清液内谷氨酰胺含量啬且在一定程度上随着ＮＨ４＾＋氨的浓度的增大而增加。然而,妾ＮＨ４＾＋２作用时间达到一定时限（７２ｈ）后,酶的活性及细胞内谷氨酰胺的量不再增加,甚至有所下降或减     

Acute tryptophan depletion in rats alters the relationship between cerebral blood flow and glucose metabolism independent of central serotonin

Acute tryptophan depletion (ATD) decreases the 5-HT precursor tryptophan (TRP) in blood and is used both clinically and preclinically to investigate the involvement of 5-HT in the development of depressive symptomatology. Depression is associated with both central 5-HT dysfunction and abnormalities in the normal relationship between regional cerebral blood flow (CBF) and glucose metabolism (CMRG). In this study, ATD was applied in Wistar rats to investigate the cerebrovascular effects of acute changes in peripheral TRP. Rats were orally fed with a protein–carbohydrate mixture, either containing or lacking TRP. Four hours later, CBF or CMRG was measured by quantitative autoradiographic imaging in 43 brain regions of interest (ROI). In plasma, ATD resulted in a 40% reduction in the ratio of TRP to the sum of other large neutral amino acids, but had no measurable effect upon TRP or 5-HT levels in hippocampus or prefrontal cortex. Nevertheless, ATD significantly reduced local CBF in 11 of the 43 brain ROIs, while local CMRG remained unchanged. Global analysis of all 43 ROIs revealed a close correlation between CBF and CMRG within both treatment groups. However, the overall ratio (=slope) after ATD (m=1.07) was significantly decreased compared to the control group (m=1.27), indicating a state of relative cerebral oligaemia. Since ATD induced a significant lowering of peripheral TRP, without affecting central TRP or 5-HT concentrations, the decrease in CBF and global change in the flow-metabolism relationship cannot be directly attributed to decreases in brain TRP availability. This could be explained if the raphe were selectively vulnerable to ATD, but the exact mechanism remains unknown. Nevertheless, these data suggest that cerebrovascular disturbances should be considered as a potential contributory factor in studies of serotonergic dysfunction, including depression, with important implications for imaging studies that use CBF alone as a measure of neuronal function.     

The management of increased intracranial pressure in children

Ten children with acute increased intracranial pressure, documented by the Cheek screw technique, were treated for Reye''s syndrome, other toxic/metabolic encephalopathies, encephalitis, and traumatic encephalopathies. The rationale for the use of hyperventilation, head position, maintenance of adequate cerebral perfusion pressure, hyperosmolar agents, steroids, adequate fluid balance, and barbiturates in the therapy of these patients is described. An analysis of these cases reveals that early monitoring of intracranial pressure, maintenance of adequate cerebral perfusion pressure, and aggressive treatment of increased intracranial pressure may reduce the mortality of patients with increased intracranial pressure. Of all patients studied, those who survived demonstrated some neurological deficit as determined by clinical examination or neuropsychological testing.     

Splanchnic circulation and metabolism in patients with acute liver failure

Acute liver failure is associated with mortality of around 50%. The aim of the present studies was to examine the circulatory and metabolic state of the splanchnic region in acute liver failure. This had not been studied previously and it could be expected that improved understanding of the pathophysiology of acute liver failure could lead to improved therapy. Hepatic plasma flow was estimated in patients with acute liver failure after development of hepatic encephalopathy grade III, by the use of liver vein catheterization and continuous infusion of sorbitol. The method was evaluated against the prerequisites of Fick's principle. Hepatic plasma flow could be estimated with sorbitol but not in all patients and the standard error of the estimated hepatic blood flow was higher than in other patient groups. In 20 patients with acute liver failure, mean hepatic blood flow was increased. At the same time, the systemic and the peripheral hemodynamics were examined. The ratio hepatic blood flow/cardiac output was increased in many patients. Lower extremity blood flow was within normal limits. Thus, low systemic vascular resistance index in acute liver failure was likely to be a consequence of vasodilatation in the muscular resistance vessels and, in particular, in the splanchnic resistance vessels. Intervention with high-volume plasmapheresis changed systemic and splanchnic hemodynamics differently, suggesting that the splanchnic vasodilatation in liver failure may by caused by a specific mechanism different from the one that leads to peripheral vasodilatation. Infusion of dopamine increased mean arterial pressure, cardiac output, and hepatic blood flow in acute liver failure. The splanchnic exchange of substrates for oxidative metabolism was examined. Splanchnic oxygen consumption was increased. The ratio splanchnic oxygen consumption/systemic oxygen consumption indicated that 1/3 of the oxygen used in the whole body in acute liver failure was used in the splanchnic region. The splanchnic metabolism of fuel substrates was abnormal. Lactate and pyruvate was released and there were no detectable gradients of free fatty acids or of the sum of amino acids. There was a small release of ketone bodies. The data suggested that the energy needs of the failing liver was covered by intracellular fat. The hypothesis of splanchnic tissue hypoxia was examined from different approaches. The normal hepatic venous oxygen saturation, the splanchnic release of both lactate and pyruvate, and a normal hepatic venous pyruvate/lactate ratio in the presence of low acetoacetate/hydroxybutyrate ratio rather indicated high substrate turnover than splanchnic tissue hypoxia. Amino acid and ammonia metabolism was examined. It was observed that arterial ammonia concentration measured after institution of mechanical ventilation was associated with cerebral herniation 1-5 days later. The background for hyperammonemia was that ammonia was released from the splanchnic circulation. The data implied that glutamine was deamidated in the gut and alanine and ammonia was released into the portal vein as during normal circumstances. Then due to severely decreased hepatic function the liver was unable to remove ammonia and alanine as it normally would. Further, the data implied that urea synthesis was impaired. Exchange of ammonia in muscle tissue was studied in 7 patients with acute liver failure and muscle tissue seems to play a major role in ammonia detoxification in acute liver failure. Treatment with high-volume plasmapheresis decreased arterial ammonia, which was likely due to increased urea production or stimulation of glutamine synthesis in muscle tissue. These findings add to our understanding of the pathophysiology and have implications for the management of acute liver failure.     

Measurements of cerebral blood flow and metabolism in patients with Alzheimer's disease

Positron emission tomography (PET) was used to measure cerebral blood flow (CBF), cerebral metabolic rate of oxygen (CMRO2), and cerebral metabolic rate of glucose (CMRglc) in patients with Alzheimer's disease. In the patients, values for CBF, CMRO2, and CMRglc have been shown to drop by 30-50% in comparison to age-matched normal controls. In the early stage (stage I), reductions in CBF and CMRO2 are prominent in the temporal and the temporoparietal cortices. In stage II, reduction in the parietal cortex also become quite prominent, and in the late stage (stage III) reduction begins prominently in the frontal cortex as well. These PET findings in Alzheimer's disease differ from those in vascular dementia, Pick's disease, and Huntington's disease. In the interrelationship among CBF, CMRO2 and higher brain function, CBF and CMRO2 decrease especially in the left frontal, the left temporal and the left parietal cortices in patients with marked language disability. On the contrary, CBF and CMRO2 decrease in the right temporal and the right parietal cortices in patients with marked apraxia and visuospatial deficits. Cerebral blood flow and metabolism are closely related to the functioning of nerve cells. Therefore we can isolate the region responsible for higher brain dysfunction and similarly evaluate the effects of treatment using cerebral blood flow and metabolism measurements.     

The effect of stepwise arterial hypotension on blood flow and oxidative metabolism of the brain

Summary With the Kety-Schmidt-technique in ten dogs anaesthetized with 0.5% halothane, blood flow and oxidative metabolism of the brain were studied during stepwise lowering of CPP due to arterial hypotension at 71 and 41 torr. CBF remained constant (65.6 and 64.1 ml/100 g min) when CPP dropped from 98 to 71 torr, but at a CPP of 41 torr CBF fell to 32.2 ml/100 g min, i. e. to about 50% of the resting value. The CMR-oxygen did not change (4.20 and 4.38 ml/100 g min) when CPP was reduced from about 100 to about 70 torr, but decreased to 2.90 ml/100 g min, i. e. about 70% of the resting value in deep arterial hypotension.The uptake of glucose changed from 4.62 to 6.19 mg/100 g min as well as the output of CO₂ and lactate (from 4.64 to 6.57 ml/100 g min and from 0.33 to 1.62 mg/100 g min) when CPP was decreased to 71 torr. It could be demonstrated that at this CPP range the oxidative metabolism was unchanged. It was assumed that the increased uptake of glucose was only to form lactate, and that this non-hypoxic lactate production was responsible for the elevated CO₂ release. At a CPP range of 41 torr the metabolic rates of glucose and CO₂ decreased to 3.33 mg/100 g min and to 3.37 ml/100 g min, respectively, while the output of lactate remained relatively high (1.14 mg/100 g min). These findings support the assumption that at a CPP range of 41 torr the oxidative metabolism of the brain becomes insufficient. All findings demonstrate close interactions between cerebral flow blood and oxidative brain metabolism in arterial hypotension. In deep arterial hypotension respiratory acidosis has an effect on CBF. The increase of CBF is accompanied by an improvement of CMR-oxygen but not of CMR-glucose. Although CMR-lactate is reduced, the lactate/glucose index remains high.