Influence of endogenous norepinephrine on cerebral blood flow and metabolism

The influence of brain norepinephrine on cerebral metabolism and blood flow was examined because exogenous norepinephrine, administered in a way that the blood-brain barrier is bypassed, has been shown to effect pronounced changes in the cerebral circulation. Reserpine (40 mug/kg, by intracarotid infusion) was administered in order to release brain norepinephrine in five anesthetized baboons. Reserpine significantly increased cerebral oxygen consumption (23%) and cerebral blood flow (50%). This response lasted for approximately 60 min. In a further five animals, effects of central beta-adrenoreceptor blockade were studied. Pro pranolol (12 mug/kg-min) produced an immediate, significant reduction in both cerebral oxygen consumption (40%) and cerebral glucose uptake (39%). Cerebral blood flow was reduced minimally. However, the responsiveness of the cerebral circulation to induced hypercapnia was severely attenuated from a gradient of 3.22 before, to 1,11 after, administration. These experiments suggest that central norepinephrine can influence the cerebral circulation primarily through noradrenergic effects on brain metabolism.     

Jugular bulb oximetry for the monitoring of cerebral blood flow and metabolism

Jugular bulb oximetry can be used to assess the balance between oxygen supply and demand to the brain, measure metabolic byproducts, and determine cerebral blood flow. It has been useful in guiding the management of patients who are at risk of developing global ischemia. In this article, the principles upon which this monitor is based are discussed. Technical considerations such as placement techniques, factors affecting accuracy, limitations of the technique, and proper interpretation of oximetric values are reviewed. Lastly, specific clinical applications are presented.     

Neuropsychological, psychiatric, and cerebral blood flow findings in vascular dementia and Alzheimer's disease

BACKGROUND AND PURPOSE: Psychiatric, neuropsychological, and cerebral blood flow differences between patients with ischemic vascular dementia (IVD) or Alzheimer's disease (AD) were examined. METHODS: A consecutive series of patients who met either the criteria of the National Institute of Neurological Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association for probable AD or the State of California AD Diagnostic and Treatment Centers criteria for probable IVD were included in the study. Twenty consecutive patients with IVD were matched for age, sex, and Mini-Mental State Examination scores with 40 consecutive patients with probable AD. Patients underwent a psychiatric interview, a neuropsychological assessment, and single-photon emission CT imaging with 99mTc-hexamethylpropyleneamine oxime. RESULTS: Patients with IVD showed significantly more severe anosognosia (P<.05) and emotional lability (P<.01) than AD patients, but no significant between-group differences were found in the frequency and severity of depression. IVD patients showed significantly more severe deficits in tests of planning, sequencing (P<.05), and verbal fluency (P<.05) as well as significantly more severe cerebral blood flow deficits in the basal ganglia (P<.01) and the frontal lobes (P<.001) than AD patients. CONCLUSIONS: Patients with IVD showed a relatively more severe dysfunction of the frontal lobes as demonstrated by single-photon emission CT and expressed in specific psychiatric and neuropsychological changes than AD patients matched for age, sex, and severity of dementia.     

Effect of acute and chronic arecoline treatment on cerebral metabolism and blood flow in the conscious rat

To investigate the structural contribution of the light chain of anti-DNA antibodies to fine specificity, the VKappa genes of two monoclonal anti-DNA antibodies, termed H241 and H102, were cloned and sequenced. H102 and H241 are independently derived from MRL-lpr/lpr mice and differ in their fine specificity: H241 binds dsDNA and normal glomeruli in vitro and deposits in the kidney in vivo, whereas H102 binds only ssDNA and does not deposit in the kidney. Both are encoded by nearly identical VH genes but different N and D regions. Our previous results have demonstrated that the VH gene for H102 and H241 encodes eight other anti-DNA antibodies that also differed in fine specificity. This suggested that the gene product encoded by the VH 102/241 gene, may have intrinsic affinity for DNA, but is unlikely to determine fine specificity or nephritogenicity. In the present study we examined whether the VKappa gene might account for the difference in nephritogenicity. The complete nucleotide and deduced amino acid sequence of VK 102 and VK241 revealed that they are very dissimilar to each other (< 60% homology). VK 241 defined a new member of the VKappa gene family and was moderately homologous to two other VK genes encoding anti-DNA antibodies and to one VK gene encoding an anti-histone antibody all from lupus strains of mice. In addition, sequence diversity in the VK CDR1 region and position 96 of the CDR3 region was observed that may be of significance in determining fine specificity. VK 102 was highly homologous to two other VKappa genes, VKs17.2 and VK C8.5, both encoding anti-DNA antibodies and members of the VK20 gene family. It was striking that all three members of the VK 20 gene family code for DNA reactivity. This suggests that certain VKappa genes may also be used to repeatedly code for anti-DNA reactivity.     

Disseminated intravascular coagulation in a case of adult onset Still's disease

We report a 82-year-old woman with adult onset Still's disease (AOSD), who presented with high fever, skin rash, swollen axillary lymph nodes, accelerated erythrocyte sedimentation rate, leukocytosis, abnormal liver function tests, hypoalbuminemia, negative antinuclear antibody and rheumatoid factor, and lack of renal involvement. Disseminated intravascular coagulation (DIC) was also diagnosed on admission. An antipyretic relieved high fever and DIC soon improved. Three years later, AOSD relapsed accompanied by hypercoagulation and hyperfibrinolysis. The patient developed subdural hematoma and DIC due to a brain contusion. High titers of serum soluble adhesion molecules and soluble thrombomodulin were noted on the first episode of DIC. These findings indicated that endothelial cells were damaged in AOSD complicated by DIC.     

Ceranapril and cerebral blood flow autoregulation

In order to investigate the levels of the polycyclic aromatic hydrocarbons, mainly benzo[a]pyrene because of its carcinogenicity, 55 samples of smoke flavour and smoked foods were analysed. The samples tested included 11 samples of liquid smoke flavour and 44 samples of smoked foods like bacon, loin, turkey, sausage, ox rib, etc. from different brands. A liquid chromatographic method was developed using a fluorescence detector. Benzo[a]pyrene was found in 73% of the liquid smoke flavour samples analysed. The levels varied from 0.1 to 336.6 micrograms/kg. Three liquid smoke flavour samples showed levels of benzo[a]pyrene above the maximum level recommended by FAO/WHO (10 micrograms/kg). From the total of 44 smoked food samples analysed, benzo(a)pyrene was detected in 23 samples (52%). The levels varied from 0.1 to 5.9 micrograms/kg. Anthracene and fluoranthene, non-carcinogenic polycyclic aromatic hydrocarbons, were found in almost all the samples analysed. Benzo[ghi]perylene, 3,4-benzofluoranthene and 1,2,3,4-dibenzopyrene were not found in any of the 55 samples analysed.     

Effect of the no-flow interval and hypothermia on cerebral blood flow and metabolism during cardiopulmonary resuscitation in dogs

BACKGROUND and PURPOSE: We sought (1) to determine the effect of brief periods of no flow on the subsequent forebrain blood flow during cardiopulmonary resuscitation (CPR) and (2) to test the hypothesis that hypothermia prevents the impact of the no-flow duration on cerebral blood flow (CBF) during CPR. METHODS: No-flow intervals of 1.5, 3, and 6 minutes before CPR at brain temperatures of 28 degreesC and 38 degreesC were compared in 6 groups of anesthetized dogs. Microsphere-determined CBF and metabolism were measured before and during vest CPR adjusted to maintain cerebral perfusion pressure at 25 mm Hg. RESULTS: Increasing the no-flow interval from 1.5 to 6 minutes at 38 degreesC decreased the CBF (18. 6+/-3.6 to 6.1+/-1.7 mL/100 g per minute) and the cerebral metabolic rate (2.1+/-0.3 to 0.7+/-0.2 mL/100 g per minute) during CPR. Cooling to 28 degreesC before and during the arrest eliminated the detrimental effects of increasing the no-flow interval on CBF (16. 8+/-1.0 to 14.8+/-1.9 mL/100 g per minute) and cerebral metabolic rate (1.1+/-0.1 to 1.3+/-0.1 mL/100 g per minute). Unlike the forebrain, 6 minutes of preceding cardiac arrest did not affect brain stem blood flow during CPR. CONCLUSIONS: Increasing the no-flow interval to 6 minutes in normothermic animals decreases the supratentorial blood flow and cerebral metabolic rate during CPR at a cerebral perfusion pressure of 25 mm Hg. Cooling to 28 degreesC eliminates the detrimental impact of the 6-minute no-flow interval on the reflow produced during CPR. The brain-protective effects of hypothermia include improving reflow during CPR after cardiac arrest. The effect of hypothermia and the impact of short durations of no flow on reperfusion indicate that increasing viscosity and reflex vasoconstriction are unlikely causes of the "no-reflow" phenomenon.     

SPECT cerebral blood flow, MR imaging, and neuropsychological findings in traumatic head injury.

Investigated 16 patients with diffuse or contusional brain damage and 8 patients with focal lesions 5–22 mo postinjury, using single proton emission computed tomography (SPECT) cerebral blood flow (CBF) measurements and neuropsychological examination. All Ss were aged 16–64 yrs. Compared with 16 controls, the diffuse group showed significant differences on 13 of 24 measures after correction for premorbid differences, whereas the focal group was significantly impaired on only 3 tests after correction. SPECT apparently identified abnormalities not demonstrated on magnetic resonance (MR) imaging and vice versa. Abnormal regional CBF seemed to be related to neuropsychological defects. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Correlation between regional cerebral blood flow and oxidative metabolism. In vivo studies in man

To test the hypothesis that regional cerebral blood flow (rCBF) is normally regulated by regional metabolic activity, rCBF and the regional cerebral metabolic rate for oxygen (rCMRO2) were compared in selected human subjects. In normal subjects and patients with chronic, stable diseases of brain, rCBF correlated well with rCMRO2. In one individual with mild dementia, rCBF and rCMRO2 were measured before and during exercise of the hand and forearm contralateral to the hemisphere studied. Appropriate parallel changes occurred in both rCBF and rCMRO2 during hand exercise. In patients with acute diseases affecting the hemisphere studied, however, the correlation between rCBF and rCMRO2 was unpredictable.     

Simultaneous measurement of [18F]FDOPA metabolism and cerebral blood flow in newborn piglets

Three diets containing either borage oil (BO) and southern hemisphere fish oil Marinol (MO), or BO and tuna orbital oil (TO), or a northern hemisphere fish oil (FO) were fed to duplicate groups of turbot (Scophthalmus maximus) of initial mean weight 1.2 g for a period of 12 weeks. The BO/MO and BO/TO diets were enriched in gamma-linolenic (18:3n-6, GLA) and eicosapentaenoic (20:5n-3, EPA) acids, and GLA and docosahexaenoic acid (22:6n-3, DHA), respectively. No differences were observed in final weights or growth rates, either between duplicate tanks or between dietary treatments. Half of the FO-fed fish sampled showed a histopathological lesion indicative of lipoid liver degeneration while the other treatments only showed a slight incidence of the same pathology. The fatty acid compositions of carcass and tissues broadly reflected the dietary input. In general, fish fed the BO/MO diet had increased levels of 18:2n-6, 18:3n-6, 20:3n-6 and 20:5n-3, but a lower level of 22:6n-3, compared to fish fed FO. In fish fed the BO/TO diet, levels of 18:2n-6, 18:3n-6, 20:3n-6 and 20:4n-6 were increased while levels of 20:5n-3 and 22:5n-3 were reduced, compared to fish fed FO. Concentrations of thromboxanes B (TXB) and leukotrienes B (LTB), derived from 20:4n-6 and 20:5n-3, were measured in plasma and stimulated blood cells. Levels of TXB2 were greatest in fish fed the BO/TO diet compared to both other treatments, while LTB4 was decreased in fish fed the BO/MO diet compared to both other treatments. In a stress test which involved anaesthesia followed by measurement of recovery times, fish fed the BO/MO diet had significantly lower recovery times compared to fish fed the FO diet.     

Carotid arterial blood flow in the ovine fetus as a continuous measure of cerebral blood flow

Principles derived from a group of 46 ML of the mantle zone are presented: Mantle pattern of a ML and its cytological structure are mostly sufficient for positive basic diagnosis. Diffuse mantle zone ML need detection of BCL-1 and CD5 hyperexpression which are characteristic for small-cell and centrocytoid forms when compared with BCL-2 positive centrofollicular lymphomas. B monocytoid lymphomas from the parafollicular subgroup as well as plasmacytoid ML from the marginal subgroup retain faint BCL-1 positivity but lose CD5 positivity. That may results in attempt of problematic narrowing of mantle zone definition because of existence of the mixed cellularity forms of mantle zone ML. Nodular mantle zone ML are clinically recognized late and are unsensitive to treatment which is opposite to the original idea of their relative benignity. M-coding of mantle zone ML is very defective because the codes do not separate nodular (perifollicular) and diffuse variants.     

The effect of remifentanil on cerebral blood flow velocity

High concentrations of lidocaine induce irreversible conduction block with little effect on resting membrane potential (Em). We assumed the mechanism of persistent neurologic deficit caused by local anesthetics may result from neural death, as represented by the loss of Em. We investigated the effects of lidocaine on Em and action potential (AP) in single crayfish giant axons in vitro. Axons were perfused with two doses of lidocaine for either 15 or 30 min, and they were continuously washed. No axons exposed to 80 mM lidocaine for 30 min showed recovery of AP and Em. Those exposed to 40 mM for 30 min and 80 mM for 15 min showed a return to baseline for Em, but no recovery of AP. Those exposed to 40 mM lidocaine for 15 min showed full recovery of Em and AP immediately after washing. The membrane depolarization was significantly greater during exposure to 80 mM lidocaine for 30 min than in other groups. We conclude that lidocaine has a direct neurotoxic effect on crayfish giant axons and that the generation of AP is more vulnerable than the maintenance of Em. The irreversibility of AP and Em is dose- and time-dependent. IMPLICATIONS: Highly concentrated lidocaine induced an irreversible conduction block and a complete loss of resting membrane potential in crayfish giant axons in vitro. Our results may represent a possible explanation for various grades of local anesthetic-induced neurotoxicity in clinical cases if the same toxicity occurs in mammalian nerves in vivo.     

Effects of phenobarbital on cerebral blood flow during hypoxia

Phenobarbital (PB), at anticonvulsant dosages, has been used in an attempt to reduce hypoxic brain injury in asphyxiated newborn infants. The effects of PB pretreatment on the cerebral blood flow (CBF) response in hypoxia were studied in 15 curarized and mechanically ventilated piglets: 7 animals were pretreated with 20 mg/kg of PB (group 1) and 8 served as untreated controls (group 2). Successive aliquots (25 ml) of carbon monoxide were introduced into a closed ventilator circuit and CBF (measured with radiolabelled microspheres), arterial blood pressure, blood gases, arterial pH and PaO2 were subsequently determined at different levels of hypoxia. The amount of hemoglobin available for oxygen transport (i.e. total Hb-HbCO) was used to express hypoxic aggression and decreased from grade I (> 2 mmol/l) to grade II (1-2 mmol/l) to grade III (< 1 mmol/l). In the control group, CBF increased during grade-I hypoxia and continuously remained above baseline values during grade-II and grade-III hypoxia. In pretreated animals, however, only grade-II hypoxia was associated with a significant increase in CBF above baseline. In addition during grade-III hypoxia, CBF decreased to the prehypoxic values despite a fall in cerebral oxygen delivery and cardiac index. These data suggest that PB should be used with caution to prevent brain damage in the asphyxiated newborn infants.     

Preictal SPECT in temporal lobe epilepsy: regional cerebral blood flow is increased prior to electroencephalography-seizure onset

Peri-ictal SPECT provides unique information on the dynamic changes in regional cerebral blood flow (rCBF) that occur during seizure evolution and, thus, could be useful in clarifying the poorly understood interplay of the interictal and ictal states in human focal epilepsy. The regional hyperperfusion observed on ictal SPECT is generally believed to be a consequence of electrical seizure activity. However, recent studies using invasive long-term cortical CBF monitoring have demonstrated that rCBF changes occur up to 20 min prior to ictal electroencephalography (EEG) onset. Because of apparent technical difficulties, no preictal SPECT studies have been reported so far. Therefore, we present our results on two patients with temporal lobe epilepsy in whom preictal SPECT scans were performed fortuitously under continuous video-EEG monitoring control. METHODS: Technetium-99m-hexamethyl propyleneamine oxime was injected 11 min (Patient 1) and 12 min (Patient 2) before clinical and EEG seizure onset, as documented from simultaneous video-EEG monitoring in two patients with temporal lobe epilepsy. We obtained accurate anatomical reference of CBF changes visible on SPECT by a special coregistration technique of MRI and SPECT. RESULTS: Whereas interictal SPECT showed a hypoperfusion of the temporal lobe ipsilateral to the seizure focus, on preictal SPECT, a significant increase in rCBF in the epileptic temporal lobe could be observed. These rCBF changes were not accompanied by any significant changes of the ongoing EEG. CONCLUSION: Our study provides evidence that rCBF is increased in the epileptic temporal lobe several minutes before EEG seizure onset. Thus, rCBF changes observed on peri-ictal SPECT scan cannot be considered a mere consequence of EEG seizure activity but may rather reflect a change in neuronal activity precipitating the transition from the interictal to the ictal state.     

Low cerebral blood flow and perfusion reserve induce hyperperfusion after surgical revascularization: case reports and analysis of cerebral hemodynamics

BACKGROUND: Hyperperfusion syndrome after surgical revascularization is a rare complication and there has not been any systematic study on factors that induce hyperperfusion after surgery. In this paper, we retrospectively analyzed the factors related to this syndrome. PATIENTS AND METHODS: We performed 46 cases of surgical revascularization including 33 cases of carotid endarterectomy (CEA) and 13 cases of superficial temporal artery-middle cerebral artery (STA-MCA) anastomosis during the past 5 years. Among these, we encountered three cases of hyperperfusion syndrome despite well-controlled blood pressure postoperatively. To evaluate factors related to the occurrence of hyperperfusion syndrome, we examined four parameters: (1) regional cerebral blood flow (rCBF), (2) the increase in the ratio of the postoperative rCBF compared to the preoperative rCBF (increase ratio), (3) cerebral perfusion reserve presented by the increase of rCBF after acetazolamide administration (delta rCBF), and (4) the difference in mean blood pressure between the preoperative and postoperative state (delta BP). RESULTS: Preoperative rCBF was significantly lower in cases of hyperperfusion syndrome than the control cases (p < 0.01 Mann-Whitney U-test). Moreover delta rCBF was evidently lower in the hyperperfusion cases than the control (p < 0.05 Fisher's exact method). However, there was no significant difference in the delta BP between the hyperperfusion cases and the control cases. CONCLUSION: In cases of marked low perfusion (low rCBF) with poor perfusion reserve (low delta rCBF), hyperperfusion after surgical revascularization can occur even if blood pressure is adequately controlled.     

Effects of a carbonic anhydrase inhibitor on cerebral blood flow in geriatric patients

A carbonic anhydrase inhibitor (UK-12,130) was shown to increase cerebral blood flow in mildly demented geriatric patients. Oral administration caused a significant increase in blood flow at two different dose levels; this persisted for at least six weeks, which was the duration of the longest study. There was no consistent improvement in mentation during treatment. Blood blow was measured by the washout of 133Xe after inhalation of this inert gas.     

Pulsatile versus nonpulsatile flow. No difference in cerebral blood flow or metabolism during normothermic cardiopulmonary bypass in rabbits

BACKGROUND: Although pulsatile and nonpulsatile cardiopulmonary bypass (CPB) do not differentially affect cerebral blood flow (CBF) or metabolism during hypothermia, studies suggest pulsatile CPB may result in greater CBF than nonpulsatile CPB under normothermic conditions. Consequently, nonpulsatile flow may contribute to poorer neurologic outcome observed in some studies of normothermic CPB. This study compared CBF and cerebral metabolic rate for oxygen (CMRO2) between pulsatile and nonpulsatile CPB at 37 degrees C. METHODS: In experiment A, 16 anesthetized New Zealand white rabbits were randomized to one of two pulsatile CPB groups based on pump systolic ejection period (100 and 140 ms, respectively). Each animal was perfused at 37 degrees C for 30 min at each of two pulse rates (150 and 250 pulse/min, respectively). This scheme created four different arterial pressure waveforms. At the end of each perfusion period, arterial pressure waveform, arterial and cerebral venous oxygen content, CBF (microspheres), and CMRO2 (Fick) were measured. In experiment B, 22 rabbits were randomized to pulsatile (100-ms ejection period, 250 pulse/min) or nonpulsatile CPB at 37 degrees C. At 30 and 60 min of CPB, physiologic measurements were made as before. RESULTS: In experiment A, CBF and CMRO2 were independent of ejection period and pulse rate. Thus, all four waveforms were physiologically equivalent. In experiment B, CBF did not differ between pulsatile and nonpulsatile CPB (72 +/- 6 vs. 77 +/- 9 ml.100 g-1.min-1, respectively (median +/- quartile deviation)). CMRO2 did not differ between pulsatile and nonpulsatile CPB (4.7 +/- 0.5 vs. 4.1 +/- 0.6 ml O2.100 g-1.min-1, respectively) and decreased slightly (0.4 +/- 0.4 ml O2.100 g-1.min-1) between measurements. CONCLUSIONS: During CPB in rabbits at 37 degrees C, neither CBF nor CMRO2 is affected by arterial pulsation. The absence of pulsation per se is not responsible for the small decreases in CMRO2 observed during CPB.     

Relations between neuropsychological findings and lateral asymmetries of cerebral blood flow measured by SPECT in dementia of Alzheimer type

We studied 16 right-handed patients clinically diagnosed as dementia of Alzheimer type (6 men, 10 women; aged 63-85, mean 72.8 years). The average duration of symptoms was 2.7 years. Dementia ranged from mild to moderately severe. None had clinical or laboratory evidence of cerebrovascular disease (Hachinski ischemic scores for all patients were 4 or below 4). All received the Wechsler Adult Intelligence Scale (WAIS), Mini-mental State Test (MMS) and Western Aphasia Battery (WAB, First Japanese edition, 1986). Regional cerebral blood flow (rCBF) was evaluated by single photon emission CT (SPECT) with 123I-N-isopropyl-p-iodoamphetamine (123I-IMP), using the Matsuda's quantitative method (Am J Physiol Imag 1: 186, 1986). Regional tracer uptake was measured in regions of interests (ROIs) over right and left frontal, temporal, parietal and occipital cortical regions; basal ganglia; and cerebellar hemispheres. The subjects were divided into three groups on the basis of lateral asymmetries in the temporal and parietal cortexes of rCBF (left < right, n = 5; right < left, n = 3; left = right, n = 8). We decided that lateral asymmetry was present when rCBF for each ROI between left and right sides differs by more than 10%. General score (MMS, T-IQ) was not correlated with asymmetry of cerebral blood flow. Verbal IQ in patients with predominant hypoperfusion of left temporal and parietal lobe was significantly lower than other group, while performance IQ and WAB constructive scores were lower in those with right hemispheric hypoperfusion (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)