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Biomedical subjects

A R Andersen

Publications and source records attributed to A R Andersen.

At least 37 records · Page 2Linked to original sources
PubMed1990

Timing and topography of cerebral blood flow, aura, and headache during migraine attacks.

Ten years of study has resulted in considerable but fragmented knowledge about regional cerebral blood flow in migraine with aura (classic migraine). In the present study, the number of repeatedly studied patients (n = 63) was large enough to determine statistically significant sequences of events and statistically significant spatial relations. The first observable event was a decrease of regional cerebral blood flow posteriorly in one cerebral hemisphere. Further development of this pathological process was accompanied by the aura symptoms. Thereafter headache occurred while regional cerebral blood flow remained decreased. During the headache phase, regional cerebral blood flow gradually changed from abnormally low to abnormally high without apparent change in headache. In some patients headache disappeared while regional cerebral blood flow remained increased. Although regional cerebral blood flow reduction and aura symptoms in the great majority of patients were unilateral, one-third had bilateral headache. Unilateral headache usually localized to the side on which regional cerebral blood flow was reduced and from which the aura symptoms originated (i.e., aura symptoms were perceived to occur contralaterally but presumably originated in the hypoperfused hemisphere). Our results suggest a simple model for migraine attacks: A pathological disturbance in one cerebral hemisphere causes the aura symptoms and after a time delay, it also causes the headache by stimulating local vascular nociceptors. Bilateral headache caused by a unilateral cerebral disturbance may be explained by recent neuroanatomical and neurophysiological findings.

Adolescent↗
PubMed1990

SPECT in the presurgical evaluation of patients with temporal lobe epilepsy--a preliminary report.

Twenty-eight patients with drug resistant temporal lobe epilepsy (DRTLE) were studied using single photon emission computed tomography (SPECT) using xenon-133 inhalation and Tc99m-d, 1-HMPAO with TOMOMATIC 64 as part of a presurgical evaluation programme. The visually evaluated flow-images were studied after blinding and the results subsequently compared to the EEG, MRI and CT scanning studies. In 24 patients a significant low flow region was seen in one temporal lobe. The SPECT result corresponded to the EEG findings in all but 6 patients. In 2 of these patients no side localization was indicated by EEG, while in four patients the EEG suggested that the opposite side was epileptogenic. Ictal SPECT and MRI/CT agreed with the resting SPECT study in three patients, while one patient has remained undiagnosed with respect to side-localization. In 14 patients discordance between SPECT and the CT scan was observed, but in 11 of these patients the SPECT study correlated with the other focal diagnostic tools. In 11 of the 21 patients studied by MRI, the results corresponded to SPECT; in 7 of the 10 which did not correspond, ictal studies of EEG and SPECT defined the side, in four of these 7 patients. Using the neuroimaging tools in concert 16 patients have been selected for surgery. All patients have benefited from surgery. These preliminary results correspond favourably with earlier studies comparing SPECT and PET with CT, MR and EEG.

Adult↗
PubMed1990

Angiotensin converting enzyme inhibition, CBF autoregulation, and ICP in patients with normal-pressure hydrocephalus.

Fourteen patients with normal pressure hydrocephalus had the autoregulation of cerebral blood flow (CBF) and intracranial pressure (ICP) investigated. In 8 of the patients the effect of Captopril on ICP and CBF was also investigated. The mean arterial blood pressure (MABP) was 109 mmHg (intra-arterially), and ICP was 11 mmHg (intraventricularly). Changes in global CBF were estimated by the arterio-venous oxygen difference method. The autoregulation of CBF was present in 13 of the patients (p less than 0.01). The lower limit of CBF autoregulation was 86% of the baseline perfusion pressure. One hour after 50 mg of captopril perorally, MABP was reduced 16 mmHg, and ICP and CBF were unchanged. The autoregulation was maintained and the lower limit was decreased 19 mmHg. Thus patients would be expected to benefit from captopril treatment in hypotensive anaesthesia.

Administration, Oral↗
PubMed1990

The effect of fosinopril sodium on cerebral blood flow in moderate essential hypertension.

The effect of the angiotensin converting enzyme (ACE) inhibitor fosinopril sodium on regional cerebral blood flow (rCBF) was investigated in 8 patients with moderate essential hypertension. A constant dose of chlorthalidone (25 mg/day) was given to stimulate the renin angiotensin system, and fosinopril sodium was given in incremental doses (10 to 40 mg/day) with the aim of obtaining a diastolic blood pressure at or below 90 mm Hg. Regional CBF was measured with xenon-133 inhalation tomography. Repetitive measurements were made at the start of treatment and again after 4 to 12 weeks treatment in the resting supine position, and during lower body negative pressure (LBNP) as a substitute for the upright position. Four hours after the first 10 mg dose of fosinopril the mean arterial pressure (MAP) had been reduced from 127 +/- 13 mm Hg to 105 +/- 9 mm Hg (P less than .01) without any significant change in mean CBF (55 +/- 9 mL/(100 g X min) at baseline versus 52 +/- 9 mL/(100 g X min) after fosinopril). After prolonged treatment with chlorthalidone and fosinopril, mean CBF was still unchanged from baseline levels, when measured 4 and 24 h after a single dose of fosinopril, despite a 10% reduction in MAP (P less than .01). LBNP did not lead to any significant change in rCBF. The regional distribution of CBF was normal in all patients throughout the study. We conclude that treatment with fosinopril sodium causes a moderate fall in blood pressure without any adverse effects on rCBF.

Adult↗
PubMed1990

Cerebral blood flow in progressive aphasia without dementia. Case report, using 133xenon inhalation, technetium 99m hexamethylpropyleneamine oxime and single photon emission computerized tomography.

We report a case of progressive aphasia without clinical signs of intellectual or behavioral impairment, satisfying Mesulam's clinical criteria of primary progressive aphasia, as 4 yrs of extensive psychometric testing and radiological imaging, comprising CT and MRI, failed to detect evidence of relevant involvement outside the left perisylvian regions. Cranial CT was normal but MRI showed multiple bilateral lesions in the deep white matter. Cerebral blood flow (CBF) studies by single photon emission computerized tomography, however, showed an initial frontotemporal focus of hypoperfusion that progressively extended to include most of the ipsilateral hemisphere and the contralateral frontal lobe. This suggests that CBF imaging may yet be the most sensitive technique in revealing subclinical injury in the degenerative brain diseases of focal onset.

Administration, Inhalation↗
PubMed1990

Computerized analysis of cerebral blood flow autoregulation in humans: validation of a method for pharmacologic studies.

Cerebral blood flow (CBF) autoregulation in the supine position without tilting using systemic ganglion-blockade (trimetaphane camphosulfonas) combined with lower body vacuum is evaluated. Automatic computerized curve-fitting analysis for assessment of the lower limit (LL) of autoregulation is introduced. Global CBF was evaluated using the arteriovenous-O2-difference method in 12 volunteers and in seven patients with chronic arterial hypertension. Classic autoregulatory curves were found in all cases. The LL of CBF autoregulation was 85 +/- 5 mm Hg in the volunteers and 113 +/- 7 mm Hg in the hypertensive patients. In seven of the volunteers, the autoregulatory study was performed twice in 1 day; a small but significant shift of LL toward higher blood pressure (BP) values was observed in the second test (3 mm Hg). In five of the hypertensive patients, regional CBF (rCBF) was measured by single-photon emission computed tomography (SPECT) of inhaled xenon-133. The median global CBF decreased from 62 to 45 ml/100 g/min during the mean arterial BP (MABP) decrease from 110 to 68 mm Hg. The regional distribution of CBF was normal at baseline as well as during hypotension. The method is suitable for pharmacologic studies of cerebral autoregulation.

Adult↗
PubMed1990

The effect of the benzodiazepine antagonist flumazenil on regional cerebral blood flow in human volunteers.

The influence of the benzodiazepine antagonist flumazenil on regional cerebral blood flow (rCBF) was investigated in ten healthy, alert volunteers. The design was a randomized, placebo-controlled, double-blind, cross-over study. rCBF was measured by 133-Xe inhalation and single photon emission computerized tomography, SPECT, immediately before, and 5 and 35 min after intravenous injection of flumazenil 1.0 mg or placebo. In addition, mean arterial blood pressures or PaCO2, rCBF were analysed for changes in various regions of interest (RoI). No alterations were found either in the global CBF or in rCBF in RoI after flumazenil injection. The results showed that a clinically active dose of flumazenil did not directly affect the cerebral circulation in the normal brain and indicated absence of significant intrinsic activity of the drug.

Adult↗
PubMed1989

Angiotensin-converting enzyme inhibition and regional cerebral blood flow in acute stroke.

The effect of the angiotensin-converting enzyme (ACE) inhibitor captopril on regional cerebral blood flow (rCBF) was studied in 12 patients within 5 days after their first acute stroke. rCBF was studied by xenon-133 inhalation and single-photon emission computed tomography (SPECT) scan before and 1 h after oral administration of 25 mg captopril. No increase in rCBF was observed in any of the 12 patients included in the study. In only one patient was there a slight redistribution of blood flow in favor of the low-flow area, but the absolute flow value did not increase. Captopril did not cause any significant change in mean hemispheric blood flow, mean arterial blood pressure (MAP), or end-expiratory CO2 fraction (FECO2). The assumption that ACE inhibition might increase cerebral blood flow in the periinfarct zone and preserve some still viable brain tissue could not be verified in the present study.

Acute Disease↗
PubMed1989

Angiotensin converting enzyme inhibition and cerebral blood flow autoregulation in normotensive and hypertensive man.

The acute effect on the lower limit of cerebral blood flow (CBF) autoregulation of an angiotensin converting enzyme (ACE) inhibitor, captopril, was studied in normotensive volunteers and in hypertensive patients. Baseline CBF was measured using xenon-133 inhalation tomography, and changes in CBF were measured using the arterio-venous oxygen difference method. Cerebral blood flow autoregulation was studied in two separate normotensive groups, one group of 12 volunteers serving as a control, and one group of 12 volunteers studied after the administration of captopril 50 mg. In a group of seven hypertensive patients CBF autoregulation was studied before and 1 h after the administration of captopril 25 mg. In the normotensive volunteers the median lower limit of CBF autoregulation was 83 and 74 mmHg in the untreated and the captopril-treated group, respectively, with no significant difference between the two groups. In five of the hypertensive patients the lower limit of CBF autoregulation was lowered by captopril, in median by 22 mmHg. However, in two patients it was increased, by 3 and 13 mmHg, respectively. It is proposed that the shift in the lower limit of CBF autoregulation seen in some of our cases, and which has previously been documented in experimental studies, may be dependent on the activity of the sympathetic nervous system.

Adult↗
PubMed1989

99mTc-D,L-hexamethylene-propyleneamine oxime (99mTc-HMPAO): basic kinetic studies of a tracer of cerebral blood flow.

The lipophilic 99mTc-D,L-hexamethylene-propyleneamine oxime (99mTc-HMPAO) has been developed for regional cerebral blood flow (rCBF) measurements by single photon emission computed tomography (SPECT). The molecule is unstable and converts rapidly from the lipophilic form, which passes the blood-brain barrier (BBB), to the hydrophilic form, which is unable to pass the BBB and is trapped in the brain. The rate-limiting step for this conversion is probably dependent on the reductant gluthathione. The lipophilic input to the brain can be estimated by rapid octanol extraction of lipophilic tracer from arterial blood. The input takes place during the first few minutes after tracer injection. The first-pass extraction from blood to brain E is high (0.72 at a CBF of 0.59 ml/g/min) in human studies as measured by the indicator dilution method. It is dependent on the CBF level and decreases when CBF increases. It is also dependent on binding to proteins and blood constituents. 99mTc-HMPAO is initially distributed like rCBF. In measuring the retention in the human brain after intravenous and intracarotid injection of 99mTc-HMPAO, an early back-diffusion (brain to blood) is seen. This lasts only 2-3 min. The back-diffusion is flow dependent, leading to a preferential loss of activity from the high flow regions of the brain. This can be corrected for by an algorithm. The effect of the algorithm is that the steady-state 99mTc-HMPAO distribution images obtained from 10 min to 2-3 h after injection of tracer agrees more closely with rCBF images as measured by reference CBF methods using SPECT and positron emission tomography (human studies) and quantitated autoradiography (rats). The retention in the brain is very stable when the early back-diffusion has ceased, and only a small loss of tracer amounting to 0.4%/h is observed in most human cases during the next 24 h. This review concludes that 99mTc-HMPAO is suitable for measurements of rCBF by SPECT. A few examples of clinical application are given.

Cerebrovascular Circulation↗
PubMed1988

Delayed hyperemia following hypoperfusion in classic migraine. Single photon emission computed tomographic demonstration.

Regional cerebral blood flow (rCBF) was measured in seven patients during classic migraine attacks. Single photon emission computed tomography was performed soon after hospital admission, and three to eight hours, 20 to 24 hours, and one week later after the onset of symptoms. Initially reduced rCBF persisting up to three hours was observed in the hemisphere appropriate to the focal neurologic deficit; hyperperfusion was noted later in the same region in these patients. At 24 hours rCBF was normal in four patients, hyperemia persisted in two patients, and one patient was not restudied. The area of interest demonstrated a mean decrease of 19% +/- 7% in side-to-side asymmetry when compared with the contralateral region. In three to eight hours this reversed to a mean increase of 19% +/- 4% (delayed hyperemia). No asymmetries were observed after one week. The late hyperemic asymmetry often persisted beyond the duration of the clinical headache. It is postulated that this tardive regional hyperperfusion is a consequence of previous focal arteriolar vasoconstriction. This vascular sequence of events further delineates the diagnostic merit of studying rCBF by noninvasive single photon emission computed tomography in migraine.

Adult↗
PubMed1988

The retention mechanism of technetium-99m-HM-PAO: intracellular reaction with glutathione.

Preparations of d,l- and meso-hexamethylpropyleneamine oxime (HM-PAO) labeled with technetium-99m were added to rat brain homogenates diluted with phosphate buffer (1:10). The conversion of d,l-HM-PAO to hydrophilic forms took place with an initial rate constant of 0.12 min-1. Incubation of the brain homogenate with 2% diethyl maleate for 5 h decreased the homogenate's measured glutathione (GSH) concentration from 160 to 16 microM and decreased the conversion rate to 0.012 min-1. Buffered aqueous solutions of glutathione rapidly converted the HM-PAO tracers to hydrophilic forms having the same chromatographic characteristics as found in the brain homogenates. The rate constant for the conversion reaction of d,l-HM-PAO in GSH aqueous solution was 208 and 317 L/mol/min in two different assay systems and for meso-HM-PAO the values were 14.7 and 23.2 L/mol/min, respectively. Rat brain has a GSH concentration of about 2.3 mM and the conversion of the d,l-HM-PAO due to GSH alone should proceed with a rate constant of 0.48 to 0.73 min-1 and be correspondingly 14-fold slower for meso-HM-PAO. In human brain, the in vivo data of Lassen et al. show a conversion rate constant of 0.80 min-1. This correspondence of values supports the notion that GSH may be important for the in vivo conversion of 99mTc-labeled HM-PAO to hydrophilic forms and may be the mechanism of trapping in brain and other cells. A kinetic model for the trapping of d,l- and meso-HM-PAO in tissue is developed that is based on data of GSH concentration in various organs.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

The retention of [99mTc]-d,l-HM-PAO in the human brain after intracarotid bolus injection: a kinetic analysis.

[99mTc]-d,l-HM-PAO (HM-PAO) was injected rapidly into the internal carotid artery and its retention in the brain was recorded by external scintillation cameras in eight human subjects. A model is described based on three compartments: the lipophilic tracer in the blood pool of the brain, the lipophilic tracer inside the brain, and the hydrophilic form retained in the brain. The retention curve initially drops abruptly, corresponding to the nonextracted fraction of the injectate leaving the brain; it then falls exponentially towards the asymptotic level of the fractional steady-state retention R. Cerebral blood flow (F) was measured using the xenon-133 intracarotid injection method. The first-pass extraction E of HM-PAO was calculated from F using an empiric regression equation. The residue curves for the whole brain after intracarotid HM-PAO injection were analyzed to yield a retention fraction (R') and the brain clearance backflux constant of lipophilic HM-PAO (k). From the kinetic model and the measured values of R', k, and F, the following parameter values could be calculated: the average retained fraction of all tracer supplied to the brain, R = 0.38 +/- 0.05 (mean +/- SD), the conversion rate constant (lipophilic to hydrophilic tracer) in the brain k3 = 0.80 +/- 0.12 min-1, the efflux rate constant (brain to blood) k2 = 0.69 +/- 0.11 min-1, the conversion/clearance ratio alpha = k3/k2 = 1.18 +/- 0.25, the influx (blood clearance) constant K1 = 0.45 +/- 0.11 ml/g/min, and the brain/blood partition ratio lambda = K1/k2 = 0.67 +/- 0.23 ml/g. Using the kinetic model and assuming constancy of alpha, an algorithm was developed that corrects for the blood flow dependent backflux of HM-PAO and results in a more linear relation between regional cerebral blood flow (rCBF) and HM-PAO distribution.

Adult↗
PubMed1988

Assessment of the arterial input curve for [99mTc]-d,l-HM-PAO by rapid octanol extraction.

The in vitro conversion of the lipophilic molecule [99mTc]-d,l-hexamethylpropyleneamine oxime [( 99mTc]-d,l-HM-PAO) to a hydrophilic form was studied in saline, plasma, and blood at 37 degrees C by paper chromatography and by octanol extraction. The octanol:saline ratio was 79.9. From this value and the corresponding octanol: plasma and octanol:blood partitioning values, an estimate of the transport of the lipophilic compound by various components of blood was made: 20% is carried in hemoglobin, 53% by the plasma proteins and 27% by the water phases of the red blood cell and plasma. Octanol extraction provided a rapid method for measuring the radiochemical purity (RCP) of lipophilic [99mTc]-d,l-HM-PAO. In saline, the RCP declined with a half-life of more than 1 h. In human plasma and whole blood, the conversion of [99mTc]-d,l-HM-PAO was biexponential due to the differences in the conversion rates of the d and l isomeric forms. The initial half-life representing the conversion rate of the l form was 1.7 min in blood and 1.4 min in plasma, while the conversion half-life of the d form was 7.4 and 24.4 min, respectively. In vivo, the RCP of arterial blood sampled after an i.v. bolus injection showed an initial peak value of 75% (68-79%) during the initial, first passage of the bolus. It declined to approximately 35% (29-40%) after 1.5 min and reached very low levels (about 1%) at 6 to 10 min. Quantitative measurements of cerebral blood flow using [99mTc]-d,l-HM-PAO necessitates a rapid method for RCP determination in arterial blood such as the one described here.

Arteries↗
PubMed1988

Extraction of [99mTc]-d,l-HM-PAO across the blood-brain barrier.

The initial extraction (E) across the blood-brain barrier (BBB) of [99mTc]-d,l-HM-PAO after intracarotid injection was measured in 14 Wistar rats and 6 patients using the double indicator, single injection method with Na-24 as the cotracer. In both series, cerebral blood flow (CBF) was measured using the initial slope of the xenon-133 washout curve after intracarotid bolus injection. In rats, bolus size (20 or 120 microliters), bolus type (saline or 10% albumin), or CBF were changed. First-pass extraction was dependent on CBF (p less than 0.001): With a small bolus of saline and at resting CBF (0.75 ml/g/min), E was 0.81, decreasing to 0.56 at a high CBF (1.5 ml/g/min). The calculated permeability surface area product (PS) increased linearly from 1.2 to 1.5 ml/g/min when CBF increased from 0.8 to 1.5 ml/g/min (p less than 0.01). E was found to increase when the bolus volume of saline was increased from 20 to 120 microliters, while using a 120 microliters bolus containing 10% albumin resulted in a decrease in E. This suggests that HM-PAO binding to albumin is not totally and rapidly reversible during a single passage through brain capillaries and that binding to blood elements may reduce the apparent extraction across brain capillaries. In patients using a bolus of 1 ml saline, E decreased linearly with increasing CBF (r = -0.81, p less than 0.001). For a CBF of 0.59 ml/g/min and an average apparent E of 0.72, an apparent PS product of 0.76 ml/g/min was calculated.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Quantitative measurements of cerebral blood flow using SPECT and [99mTc]-d,l-HM-PAO compared to xenon-133.

The uptake and retention in a 2 cm thick brain section was recorded serially by SPECT after i.v. injection of [99mTc]-d,l-HM-PAO (HM-PAO). In 16 patients, the fraction of the administered dose retained by the brain was 5.2 +/- 1%, showing a peak after 40-50s, then decreasing by 10% within the first 10 min and then by only 0.4% per hour. The image contrast was measured in each patient as the regional hemispheric asymmetry difference in percent of the highest value of the two regions. It decreased from 31% at 30-40 s to 25% at 10 min. At 24 h, a value of 19% was reached. Using the images obtained at 10 min after injection, a region to region comparison of the original and corrected HM-PAO images to the xenon-133 regional cerebral blood flow (rCBF) images was performed. Forty-four patients with stroke, epilepsy, dementia, basal ganglia disease, and tumors and control subjects were included in this comparison. The algorithm proposed by Lassen et al. was used to correct the original images for back diffusion of tracer (brain to blood); a good correlation very close to the line of identity between the corrected HM-PAO and xenon-133 data was obtained when using a conversion/clearance ratio of 1.5 and when the noninvolved hemisphere was used as a reference region (r = 0.86, p less than 0.0001). Serial arterial and cerebral venous blood sampling was performed over 10 min following i.v. injection of HM-PAO in six patients. An overall brain retention fraction of 0.37 +/- 0.03 (mean +/- SEM) was calculated from the data. An average CBF of 0.62 +/- 0.12 ml/g/min was determined on the basis of the Fick principle; this compared to a value of 0.59 +/- 0.09 ml/g/min (mean +/- SEM) measured by the xenon-133 inhalation method. The two sets of CBF values correlated linearly with a correlation coefficient of 0.97 (p less than 0.01). Inserting the average CBF value for the hemisphere as measured by the Fick principle into the algorithm described by Lassen et al. yields absolute rCBF values (ml/g/min) directly from the corrected HM-PAO images.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1988

SPECT with [99mTc]-d,l-hexamethyl-propylene amine oxime (HM-PAO) compared with regional cerebral blood flow measured by PET: effects of linearization.

In order to validate the use of technetium-99m-d,l-hexamethylpropyleneamine oxime (HM-PAO) as a flow tracer, a total of 21 cases were studied with single photon emission computerized tomography (SPECT), and compared to regional cerebral blood flow (rCBF) measured by position emission tomography (PET) using the oxygen-15 CO2 inhalation technique. Although HM-PAO SPECT and rCBF PET images showed a similar distribution pattern the HM-PAO SPECT image showed less contrast between high and low activity flow regions than the rCBF image and a nonlinear relationship between HM-PAO activity and rCBF was shown. Based on the assumption of flow-dependent backdiffusion of HM-PAO from the brain, we applied a "linearization algorithm" to correct the HM-PAO SPECT images. The corrected HM-PAO SPECT images revealed a good linear correlation with rCBF (r = 0.901, p less than 0.001). The results indicated HM-PAO can be used as a flow tracer with SPECT after proper correction.

Adult↗