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Biomedical subjects

G M Knudsen

Publications and source records attributed to G M Knudsen.

At least 19 recordsLinked to original sources
PubMed2002

Cerebral blood flow, oxidative metabolism and cerebrovascular carbon dioxide reactivity in patients with acute bacterial meningitis.

BACKGROUND: The optimal arterial carbon dioxide tension (P(a)CO(2)) in patients with acute bacterial meningitis (ABM) is unknown and controversial. The objective of this study was to measure global cerebral blood flow (CBF), cerebrovascular CO(2) reactivity (CO(2)R), and cerebral metabolic rates (CMR) of oxygen (O(2)), glucose (glu), and lactate (lac), in patients with ABM and compare the results to those obtained in healthy volunteers. METHODS: We studied 19 patients (17 of whom were sedated) with ABM and eight healthy volunteers (controls). CBF was measured during baseline ventilation and hyperventilation with single-photon emission computed tomography (SPECT) (14 patients) and/or the Kety-Schmidt technique (KS) (11 patients and all controls). In KS studies, CMR was measured by multiplying the arterial to jugular venous concentration difference (a-v D) by CBF. RESULTS: CBF did not differ significantly among groups, although a larger variation was seen in patients than in controls. CO(2)R was not significantly different among groups. At baseline, patients had significantly lower a-v DO(2), CMR(O(2)), CMR(glu), and CMR(lac) than controls. CMR(O(2)) did not change between hyperventilation compared to baseline ventilation, whereas CMR(glu) increased. CONCLUSION: In patients with acute bacterial meningitis, we found variable levels of CBF and cerebrovascular CO(2) reactivity, a low a-v DO(2), low cerebral metabolic rates of oxygen and glucose, and a cerebral lactate efflux. In these patients, a ventilation strategy guided by jugular bulb oximetry and/or repeated CBF measurements may be more optimal in terms of cerebral oxygenation than a strategy aiming at identical levels of P(a)CO(2) for all patients.

Adult↗
PubMed2001

Serotonin induces a decrease of 5-HT(1A) immunoreactivity in organotypic hippocampal cultures.

Serotonin reuptake inhibitors used for the treatment of depression act by increasing serotonin levels at the synaptic cleft and thereby activating 5-HT(1A) serotonin receptors. However, the effect of increased levels of serotonin on postsynaptic 5-HT(1A) receptor density is unknown. The purpose of this study was to investigate, in a culture model, how postsynaptic 5-HT(1A) receptors are influenced by serotonin. Different concentrations of serotonin (0.5, 1, 10, 50 and 100 microM) were added to organotypic hippocampal cultures and incubated for 1 week. The cultures were immunostained for the 5-HT(1A) receptor and the staining analyzed densitometrically. 5-HT(1A) levels decreased with increasing serotonin concentrations, being significant at 10, 50 and 100 microM. These results indicate that at increasing serotonin levels the density of postsynaptic 5-HT(1A) receptors is down-regulated.

Animals↗
PubMed2001

Binding characteristics of selective serotonin reuptake inhibitors with relation to emission tomography studies.

When developing ligands for emission tomography studies, one of the major obstacles lies in the selection of ligand candidates. A previously unattended factor such as the influence of temperature on candidate ligand affinity is likely to play a role. By use of rat brain homogenates, the binding characteristics of [(3)H]-(S)-citalopram and [(3)H]-(+)-McN5652 and the receptor-ligand interaction at the serotonin transporter of 17 selective serotonin reuptake inhibitors were compared at 21 degrees C and 37 degrees C, respectively. Ligand logP values were also calculated. The ratios for K(i) at 37 degrees C vs. 21 degrees C varied between 0.2 and 2.2 for the selective serotonin reuptake inhibitors considered in this study, with most of the ligands displaying an inverse relationship between K(i) and temperature. Ten of the 17 selective serotonin reuptake inhibitors were found to have pK(i) values statistically significantly different at 21 degrees C compared to 37 degrees C (P < 0.05). The logP values ranged between 3.6 and 4.8, except for DASB, 5-iodo-6-nitroquipazine, and paroxetine where logP was 1.9, 2.2, and 5.0, respectively. K(d) was 0.71 nM at 37 degrees C and 0.31 nM at 21 degrees C for [(3)H]-(S)-citalopram. For [(3)H]-(+)-McN5652 K(d) was 0.11 nM at 37 degrees C and 0.08 nM at 21 degrees C. The association and dissociation was much faster for [(3)H]-(S)-citalopram as compared to [(3)H]-(+)-McN5652. It is concluded that temperature may affect K(d) differently and that in vitro dissociation may help to predict whether a given ligand may be useful in PET studies. LogP values do not per se predict the potential of a given ligand as an emission tomography tracer.

Animals↗
PubMed2001

Idiopathic normal-pressure hydrocephalus: evaluation and findings in a multidisciplinary memory clinic.

The diagnostic evaluation of patients with possible idiopathic normal-pressure hydrocephalus (INPH) is traditionally performed in the settings of either neurological, neurosurgical or psychiatric departments. The diagnostic procedure and findings in 71 consecutive patients referred with a clinical and radiological suspicion of INPH to our out-patient multidisciplinary memory clinic are evaluated. Primary diagnoses and potential concomitant disorders considered of secondary importance for the symptomatologies were established. Abnormal hydrodynamics, demonstrated by intraventricular pressure monitoring and infusion test were mandatory for the diagnosis of INPH. Mean age was 68 years and mean Mini-Mental State Examination (MMSE) score was 22. DSM IV criteria of dementia were fulfilled in 42%. In half of the referred patients (n=36), the suspicion of INPH was already disproved subsequently to the evaluation programme performed in the outpatient clinic. The main primary diagnosis was cerebrovascular disease (CVD) comprising 27% (n=19) of the referrals, whereas INPH was diagnosed in only 20% (n=14). Shunt improvement rate was 72%. The remaining patients were diagnosed as having one of 26 different conditions. A multiplicity of disorders mimics the INPH syndrome, with CVD being the primary differential diagnosis. Evaluating patients with possible INPH in an outpatient multidisciplinary memory clinic is an effective and rational diagnostic approach.

Adult↗
PubMed2001

Cerebral metabolism of ammonia and amino acids in patients with fulminant hepatic failure.

BACKGROUND & AIMS: High circulating levels of ammonia have been suggested to be involved in the development of cerebral edema and herniation in fulminant hepatic failure (FHF). The aim of this study was to measure cerebral metabolism of ammonia and amino acids, with special emphasis on glutamine metabolism. METHODS: The study consisted of patients with FHF (n = 16) or cirrhosis (n = 5), and healthy subjects (n = 8). Cerebral blood flow was measured by the 133Xe washout technique. Blood samples for determination of ammonia and amino acids were drawn simultaneously from the radial artery and the internal jugular bulb. RESULTS: A net cerebral ammonia uptake was only found in patients with FHF (1.62 +/- 0.79 micromol x 100 g(-1) x min(-1)). The cerebral glutamine efflux was higher in patients with FHF than in the healthy subjects and cirrhotics, -6.11 +/- 5.19 vs. -1.93 +/- 1.17 and -1.50 +/- 0.29 micromol x 100 g(-1) x min(-1), respectively (P < 0.05). Patients with FHF who subsequently died of cerebral herniation (n = 6) had higher arterial ammonia concentrations, higher cerebral ammonia uptake, and higher cerebral glutamine efflux than survivors. Intervention with short-term mechanical hyperventilation in FHF reduced the net cerebral glutamine efflux, despite an unchanged net cerebral ammonia uptake. CONCLUSIONS: Patients with FHF have an increased cerebral glutamine efflux, and short-term hyperventilation reduces this efflux. A high cerebral ammonia uptake and cerebral glutamine efflux in patients with FHF were associated with an increased risk of subsequent fatal intracranial hypertension.

Adult↗
PubMed2001

Transcranial Doppler sonography and internal jugular bulb saturation during hyperventilation in patients with fulminant hepatic failure.

Mechanical hyperventilation is often used to postpone or ameliorate intracranial hypertension in patients with fulminant hepatic failure (FHF). Because such treatment may critically reduce cerebral blood flow (CBF), bedside techniques to monitor CBF are warranted. In this study, we evaluated the efficacy of transcranial Doppler (TCD) sonography of the middle cerebral artery (MCA) and internal jugular bulb saturation (svJO(2)) to determine relative changes in CBF during mechanical hyperventilation in 8 patients with FHF (median age, 40 years; range, 20 to 54 years). We found that TCD and svJO(2) decreased during hyperventilation in parallel with CBF, determined by the xenon 133 ((133)Xe) washout technique. Quantitatively, the TCD method was less accurate to determine carbon dioxide (CO(2)) reactivity compared with svJO(2) and the (133)Xe technique. This indicates a slight change in MCA diameter during hyperventilation. We conclude that TCD and svJO(2) monitoring may give valuable information on relative changes in CBF during hyperventilation. However, the TCD method appears less accurate for quantitative estimation of CO(2) reactivity in patients with FHF.

Adult↗
PubMed2001

S-100b and neuron-specific enolase in patients with fulminant hepatic failure.

Patients with fulminant hepatic failure (FHF) frequently develop cerebral edema and intracranial hypertension. The aim of this study was to evaluate circulating S-100b and neuron-specific enolase (NSE) levels as markers of neurological outcome in patients with FHF. In a subgroup of patients, the cerebral flux of S-100b and NSE was measured. We included 35 patients with FHF, 6 patients with acute on chronic liver disease (AOCLD), 13 patients with cirrhosis of the liver without hepatic encephalopathy, and 8 healthy subjects. Blood samples were obtained from catheters placed in the radial artery and internal jugular bulb. The net cerebral flux of S-100b and NSE was measured, and the effect of short-term hyperventilation, as well as the effect of high-volume plasmapheresis, on circulating levels of these two biomarkers was determined. Blood levels of S-100b were greater in patients with FHF and AOCLD than patients with cirrhosis and healthy subjects (median, 0.39 microg/L; range, 0.02 to 10.31 microg/L; and 1.11 microg/L; range, 0.19 to 4.84 microg/L v 0.05 microg/L; range, 0.02 to 0.27 microg/L; and 0.09 microg/L; range, 0.02 to 0.15 microg/L, respectively; P <.05, ANOVA). Among patients with FHF, blood levels of NSE tended to be greater in patients who subsequently developed cerebral herniation than in survivors (median, 10.5 microg/L; range, 5.2 to 15.9 microg/L v 5.1 microg/L; range, 2.8 to 12 microg/L; P =.05). There was no net cerebral flux of S-100b or NSE. Short-term hyperventilation had no effect on any of these measures, whereas high-volume plasmapheresis reduced circulating S-100b levels from 0.45 microg/L (range, 0.19 to 10.31 microg/L) to 0.42 microg/L (range, 0.11 to 6.35 microg/L; P =.01). In conclusion, blood levels of S-100b were elevated in almost all patients with FHF and AOCLD, but were unrelated to survival. Conversely, NSE showed a clear tendency toward greater circulating levels in patients with FHF who subsequently developed cerebral herniation than in survivors. This finding encourages further evaluation of NSE as a marker of neurological outcome in FHF.

Acute Disease↗
PubMed2001

In vivo measurement of haloperidol affinity to dopamine D2/D3 receptors by [123I]IBZM and single photon emission computed tomography.

This study examines the feasibility of a steady-state bolus-integration method with the dopamine D2/D3 receptor single photon emission computer tomography (SPECT) tracer, [123I]IBZM, for determination of in vivo affinity of haloperidol. The nonspecific binding of [123I]IBZM was examined in the rat brain by infusion of haloperidol to plasma levels approximately 100 times the Kd level in man. In humans, Kd for haloperidol binding was measured in four healthy volunteers that were examined twice: once with partial dopamine D2/D3 receptor blockade obtained by a scheduled infusion of unlabeled haloperidol (0.7 mg total dosage), and once in an unblocked state. Blood sampling and SPECT were performed intermittently during 6 hours after intravenous [123I]IBZM bolus injection. Plasma [123I]IBZM was determined by octane extraction. Plasma haloperidol was determined by a radioimmunoassay, and plasma protein binding was determined by equilibrium dialysis. In humans, the striatal D2/D3 receptor occupancy was 0.27+/-0.085 and the in vivo Kd for haloperidol was 0.25+/-0.1 nmol/L, which is comparable to Kd values as obtained from in vitro studies. The authors conclude that steady-state [123I]IBZM SPECT studies allow for determination of dopamine D2/D3 receptor occupancy in striatum and in vivo measurement of drug affinity to striatal dopamine D2 and D3 receptors.

Adult↗
PubMed2001

The (18)F-fluorodeoxyglucose lumped constant determined in human brain from extraction fractions of (18)F-fluorodeoxyglucose and glucose.

Quantification of regional cerebral glucose metabolism (CMRglc) using positron emission tomography and 18F-fluorodeoxyglucose (PET-FDG) requires knowledge of the correction factor between FDG and glucose net clearance, the FDG lumped constant (LC). Because diverging values for LC have been obtained, the authors reevaluated LC by measuring the ratio of the cerebral net extraction fractions of FDG (E*) and glucose (E) from arteriovenous cerebral measurements. Thirty subjects were studied (mean age = 25 +/- 4 years): 12 during a programed infusion of FDG and 18 after a bolus injection of FDG. In the infusion study, LC was calculated as the ratio E*/E. In the bolus study, E* was calculated from the slope of a Patlak-Gjedde plot. Lumped constant was significantly smaller in the infusion study as compared with the bolus study (0.48 +/- 0.16 vs. 0.81 +/- 0.27, P < 0.001). In 4 subjects studied during continuous FDG infusion for 2.5 hours, LC decreased to 0.36 +/- 0.11. These results suggest that the "steady-state" method underestimates LC because E* continues to decline because of significant labeled product. Further, the authors provide evidence for resetting of LC toward a greater value. The subsequent resetting of CMRglc provides a physiologically more meaningful estimate and allows for comparison of CMRglc values between different methodologies.

Brain↗
PubMed2001

Benzodiazepine receptor quantification in Huntington's disease with [(123)I]omazenil and SPECT.

OBJECTIVES: Increasing evidence suggests that metabolic changes predate neuronal death in Huntington's disease and emission tomography methods (PET and SPECT) have shown changes in glucose consumption and receptor function in early and possibly even presymptomatic disease. Because the GABA(A)-benzodiazepine receptor complex (BZR) is expressed on virtually all cerebral neurons BZR density images may be used to detect neuronal death. In this study the regional cerebral [(123)I]iomazenil binding to BZR was determined in patients with Huntington's disease and normal controls by a steady state method and SPECT. METHODS: Seven patients mildly to moderately affected by Huntington's disease and seven age matched controls were studied. Brain CT was performed on all subjects. In each subject two [(123)I]iomazenil-SPECT measurements were acquired-one with and one without infusion of flumazenil. The affinity constant of flumazenil (Kd) was calculated from the paired distribution volumes (DV) and the free plasma flumazenil concentration. The distribution volume of [(123)I]iomazenil in the unblocked condition (DV(0)) reflects the ratio between BZR density and Kd. RESULTS: Flumazenil Kd was similar in the Huntington's disease group and the control group (11.3 v 11.2 mM). For the Huntington's disease group a 31% reduction in striatal DV(0) (p=0.03) was found. In the cortical regions, DV(0) was similar in patients and in controls. In Huntington's disease, DV(0) correlated significantly with functional capacity (p=0.04) and chorea symptoms (p=0.02). The clinically least affected patients displayed DV(0)s within the range of those of the control group (19-35 ml/ml). CONCLUSIONS: The finding of an unchanged Kd of flumazenil in patients indicates that the BZR is functionally intact in Huntington's disease. That is, the reduction in DV(0) for BZR represents a selective decrease in the number of striatal BZRs. DV(0) significantly correlated with functional loss and [(123)I]iomazenil-SPECT could be an important tool for validation of the effect of future therapeutic strategies aimed at limiting oxidative stress and free radicals in Huntington's disease.

Adult↗
PubMed2001

Autoregulation of cerebral blood flow in patients resuscitated from cardiac arrest.

BACKGROUND AND PURPOSE: Under normal circumstances, autoregulation maintains cerebral blood flow (CBF) constant within a wide range of mean arterial pressure (MAP). It remains unknown whether patients resuscitated from cardiac arrest have preserved CBF autoregulation. In this study, CBF autoregulation was investigated within the first 24 hours after resuscitation from cardiac arrest. METHODS: Eighteen patients and 6 healthy volunteers had relative changes in CBF determined by transcranial Doppler mean flow velocity (V(mean)) in the middle cerebral artery during a stepwise rise in MAP by use of norepinephrine infusion. V(mean) was plotted against MAP, and a lower limit of autoregulation was identified by double regression analysis based on the least-squares method. RESULTS: In patients, V(mean) increased from a median of 33 (range 19 to 73) to 37 (22 to 100) cm/s (P:<0.001) during a norepinephrine-induced rise in MAP from 78 (46 to 118) to 106 (60 to 149) mm Hg. Eight of 18 patients had impaired CBF autoregulation, and in 5 of the 10 patients with preserved CBF autoregulation, the lower limit of autoregulation could be identified. The lower limit of CBF autoregulation was 76 mm Hg (41 to 105 mm Hg) in the volunteers and 114 mm Hg (80 to 120 mm Hg) in the 5 patients with preserved autoregulation (P:<0.01). CONCLUSIONS: We conclude that in a majority of patients in the acute phase after cardiac arrest, cerebral autoregulation is either absent or right-shifted. These results indicate that MAP should be kept at a higher level than commonly accepted to secure cerebral perfusion. We recommend, however, that further randomized clinical trials are performed to determine whether sympathomimetic drugs improve neurological outcome.

Adult↗
PubMed2001

Cerebral blood flow in patients with chronic heart failure before and after heart transplantation.

BACKGROUND AND PURPOSE: Arterial blood pressure and cardiac output are often reduced in patients with chronic heart failure (CHF). Counterregulatory mechanisms with increased neurohormonal activation and changes in the distribution of cardiac output are assumed to secure vital organ perfusion. However, clinical examination of patients with CHF frequently reveals neurological symptoms with dizziness and memory problems, suggesting altered brain perfusion. In this study we determined whether cerebral blood flow (CBF) is reduced in patients with New York Heart Association (NYHA) functional class III and IV (n=12) compared with healthy control subjects (n=12). Furthermore, we examined whether heart transplantation (n=5) could restore CBF. METHODS: CBF was estimated by single-photon emission computed tomography and (133)Xe as tracer, and middle cerebral artery velocity was measured by transcranial Doppler ultrasound. RESULTS: In the CHF patients, CBF was 36+/-1 mL/min per 100 g, corresponding to a 31% reduction compared with the control group (52+/-5 mL/min per 100 g) (P<0.05). After heart transplantation, CBF increased from 35+/-3 mL/min per 100 g before transplantation to 50+/-3 mL/min per 100 g within the first postoperative month (P<0.05). CONCLUSIONS: We conclude that CBF is substantially, but reversibly, reduced in patients with NYHA class III/IV heart failure. This phenomenon suggests that redistribution of cardiac output inadequately secures brain perfusion in patients with severe CHF.

Blood Flow Velocity↗
PubMed2001

Single photon emission computed tomography and apolipoprotein E in Alzheimer's disease: impact of the epsilon4 allele on regional cerebral blood flow.

The aim of this study was to examine the impact of the apolipoprotein E (APOE) epsilon4 allele on semiquantitative regional cerebral blood flow (rCBF) in Alzheimer's disease. Single photon emission computed tomography technetium (SPECT) with (99m)Tc d,l-hexamethyl propylenamine oxine was used to determine rCBF in 41 consecutive patients (18 males/23 females) with probable Alzheimer's disease according to the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria (mean age 71.0 years; range 54-85). The mean Mini-Mental State Examination (MMSE) score was 20.4 (range 10-30). After normalization of CBF to mean blood flow in the cerebellum, values for rCBF in several cortical regions of interest, side-to-side asymmetry indices, and anterior-posterior ratios were calculated. Determination of the APOE genotype from blood samples was performed using restriction enzyme polymerase chain reaction technique. Multivariate regression analyses and the Wilcoxon rank-sum test for unpaired data (Mann-Whitney) were used for statistical analysis. The patients comprised 27APOE epsilon4-positive and 14APOE epsilon4-negative individuals. Five patients were APOE epsilon4 homozygotes. APOE epsilon4-positive patients had significantly reduced rCBF in the right frontal and left occipital lobes. On nonparametric analysis, the most prominent differences between epsilon4-negative and epsilon4-positive patients were demonstrated in subregions representing the frontal association cortex (Mann-Whitney, P < .01). Age-stratified analysis suggested that these findings could be demonstrated predominantly in the elderly patients. The results of this study suggest that the APOE genotype in itself may have an impact on the pattern of rCBF deficits in Alzheimer's disease. The more pronounced reduction of rCBF in frontal association cortex observed in elderly APOE epsilon4-positive patients might predict clinical progression.

Age Factors↗
PubMed2001

Blood-brain barrier transport and brain metabolism of glucose during acute hyperglycemia in humans.

It is controversial whether transport adaptation takes place in chronic or acute hyperglycemia. Blood-brain barrier glucose permeability and regional brain glucose metabolism (CMR(glc)) was studied in acute hyperglycemia in six normal human subjects (mean age, 23 yr) using the double indicator method and positron emission tomography and [(18)F]fluorodeoxyglucose as tracer. The Kety-Schmidt technique was used for measurement of cerebral blood flow (CBF). After 2 h of hyperglycemia (15.7 +/- 0.7 mmol/L), the glucose permeability-surface area product from blood to brain remained unchanged (0.050 +/- 0.008 vs. 0.059 +/- 0.031 mL/100 g.min). The unidirectional clearance of [(18)F]fluorodeoxyglucose (K(1)*) was reduced from 0.108 +/- 0.011 to 0.061 +/- 0.005 mL/100 g.min (P < 0.0004). During hyperglycemia, global CMR(glc) remained constant (21.4 +/- 1.2 vs. 23.1 +/- 2.2 micromol/100 g.min, normo- and hyperglycemia, respectively). Except for a significant increase in white matter CMR(glc), no regional difference in CMR(glc) was found. Likewise, CBF remained unchanged. The reduction in K(1)* was compatible with Michaelis-Menten kinetics for facilitated transport. Our findings indicate no major adaptational changes in the maximal transport velocity or affinity to the blood-brain barrier glucose transporter. Finally, hyperglycemia did not change global CBF or CMR(glc).

Adult↗
PubMed2000

Dopamine D(2) receptor quantification in extrastriatal brain regions using [(123)I]epidepride with bolus/infusion.

The iodinated benzamide epidepride, which shows a picomolar affinity binding to dopamine D(2) receptors, has been designed for in vivo studies using SPECT. The aim of the present study was to apply a steady-state condition by the bolus/infusion approach with [(123)I]epidepride for the quantification of striatal and extrastriatal dopamine D(2) receptors in humans. In this way the distribution volume of the tracer can be determined from a single SPECT image and one blood sample. Based on bolus experiments, an algorithm using conventional convolution arguments for prediction of the outcome of a bolus/infusion (B/I) experiment was applied. It was predicted that a B/I protocol with infusion of one-third of the initial bolus per hour would be appropriate. Steady-state conditions were attained in extrastriatal regions within 3-4 h but the infusion continued up to 7 h in order to minimize the significance of individual differences in plasma clearance and binding parameters. A steady-state condition, however, could not be attained in striatal brain regions using a B/I protocol of 20 h, even after 11 h. Under near steady-state conditions a striatal:cerebellar ratio of 23 was demonstrated. Epidepride has a unique signal-to-noise ratio compared to [(123)I]IBZM but present difficulties for steady-state measurements of striatal regions. The bolus/infusion approach is particularly feasible for quantification of the binding potential in extrastriatal regions.

Adult↗
PubMed2000

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.

Adult↗
PubMed2000

Cerebral perfusion, cardiac output, and arterial pressure in patients with fulminant hepatic failure.

OBJECTIVE: To evaluate whether changes in cardiac output influence cerebral perfusion directly. In fulminant hepatic failure, the circulation is characterized by wide variations in cardiac output and cerebral blood flow (CBF). DESIGN: A retrospective, interindividual analysis of CBF and cardiac output (part 1) and a prospective evaluation of cerebral perfusion, cardiac output, and arterial pressure during norepinephrine infusion (part 2). SETTING: A four-bed specialist liver failure unit. PATIENTS AND INTERVENTIONS: Twenty patients with fulminant hepatic failure (median age, 43 yrs; range, 17-54; 13 women) maintained on mechanical ventilation (Paco2, 33 torr [4.40 kPa]; range, 26-36 torr [3.47-4.80 kPa) after development of hepatic encephalopathy, stages 3 to 4, had mean arterial pressure (MAP) and cardiac output determined by radial and pulmonary artery catheters. Cerebral perfusion was measured by the 133Xenon clearance technique (n = 8) and by transcranial Doppler sonography, which was used to measure mean flow velocity (Vmean). CBF and Vmean in patients with high cardiac output (>9 L/min) were compared with those with normal or low cardiac output. In the second part of the study, cerebral autoregulation was evaluated by concomitant measurement of Vmean, cardiac output, and MAP during norepinephrine infusion in nine patients. MEASUREMENTS AND MAIN RESULTS: Median cardiac output was 8.5 L/min (range, 3.2-17.3), CBF was 33 mL/100 g/min (12-77 g/min), and Vmean was 45 cm/sec (22-65 cm/sec). In patients with elevated cardiac output, MAP, Vmean, and CBF were similar compared with patients with normal cardiac output. Neither CBF nor Vmean correlated to cardiac output. During norepinephrine infusion, Vmean increased from 49 cm/sec (34-69 cm/sec) to 63 cm/sec (58-90 cm/sec; p < .05), as MAP increased from 75 mm Hg (54-105 mm Hg) to 97 mm Hg (90-128 mm Hg). On average, cardiac output remained unchanged at 5.7 L/min (range, 3.2-17.3), as it increased in five patients and decreased in four patients. The change in Vmean was related to MAP (r2 = .76; p < .01) but not to cardiac output (r2 = .01). CONCLUSION: This study shows that CBF correlates to arterial pressure rather than to cardiac output in patients with fulminant hepatic failure. The presence of pressure-passive cerebral circulation stresses the importance of strict cardiovascular control in securing continuous and sufficient cerebral oxygenation and in avoiding the development of cerebral hyperemia and cerebral edema.

Adolescent↗