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Biomedical subjects

N A Lassen

Publications and source records attributed to N A Lassen.

At least 37 records · Page 2Linked to original sources
PubMed1995

[Treatment of high blood pressure in patients with acute apoplexy].

The study was performed to investigate how often reduction of high blood pressure (> or = 220 mmHg systolic and or > or = 120 mmHg diastolic) was attempted in patients with acute stroke or transient ischemic attacks (TIA). Of 1351 consecutive patients with acute stroke or TIA 119 had high blood pressure on admission. In 15 patients the stroke was so severe that treatment was not considered. In the remaining 104 patients reduction of the blood pressure was attempted in 28 (27%); in 23 patients immediately following admission. None of the patients had symptoms or signs of hypertensive encephalopathy. It is concluded that reduction of high blood pressure in patients with stroke or TIA is attempted too often. As autoregulation is commonly impaired in acute stroke, reduction of systemic blood pressure may enhance ischaemic tissue damage. Reduction of blood pressure in acute stroke should be considered only in case of hypertensive encephalopathy.

Acute Disease↗
PubMed1995

[Reducing hypertension may worsen symptoms of acute apoplexy].

Patients with acute stroke often present with high blood pressure (BP) on hospital admission. Because hypertension is a risk factor for stroke, and because severe BP elevation may increase oedema and the risk of haemorrhage, acute antihypertensive therapy might seem reasonable. On the other hand, the increase in BP in the acute stage might be considered a beneficial pathophysiological response maintaining the perfusion pressure to the ischaemic area and, in particular, the surrounding penumbra. As illustrated in the case presented here, lowering the BP in the early stage may be associated with progression of neurological deficits, very likely due to a reduction of perfusion to the penumbra thus enlarging the infarct.

Acute Disease↗
PubMed1995

Benzodiazepine receptor quantification in vivo in humans using [11C]flumazenil and PET: application of the steady-state principle.

Carbon-11-labeled flumazenil combined with positron emission tomography (PET) was used to measure the concentration (Bmax) of the benzodiazepine (Bz) receptor in the brain and its equilibrium dissociation constant (KD) for flumazenil in five normal subjects. The steady-state approach was used injecting the tracer as a bolus of high specific activity. In each subject two studies were carried out. The first study was performed at essentially zero receptor occupancy, the tracer alone study. The second study was performed at a steady-state receptor occupancy of about 50%, achieved by a prolonged constant infusion of nonlabeled ("cold") flumazenil starting 2h before the bolus tracer injection and continuing until the end of scanning period. In this second study the free concentration of unmetabolized flumazenil in plasma water was measured in multiple blood samples. The observed tissue and plasma tracer curves, calibrated in the same units of radioactivity per millimeter, were analyzed in two ways: (a) by the noncompartmental (stochastic) approach making no assumptions regarding number of compartments in the tissue, and (b) by the single-compartment approach assuming rapid exchange (mixing) of tracer between all tissue compartments. The noncompartmental and the compartmental analyses gave essentially the same values for the distribution volume of the tracer, the parameter used for quantitation of the Bz receptor. As the compartmental approach could be applied to a shorter observation period (60 min instead of 120 min) it was preferred. The five subjects had a mean KD value of 12 nM/L of water and Bmax values of the grey matter ranging from 39 +/- 11 in thalamus to 120 +/- 14 nM/L of brain in occipital cortex. Most previous studies have been based on the pseudoequilibrium approach using the brain stem as a receptor-free reference region. This yields practically the same KD but lower Bmax values than the steady-state approach presented here.

Adult↗
PubMed1995

Persistent resetting of the cerebral oxygen/glucose uptake ratio by brain activation: evidence obtained with the Kety-Schmidt technique.

Global cerebral blood flow (CBF), global cerebral metabolic rates for oxygen (CMRO2), and for glucose (CMRglc), and lactate efflux were measured during rest and during cerebral activation induced by the Wisconsin card sorting test. Measurements were performed in healthy volunteers using the Kety-Schmidt technique. Global CMRO2 was unchanged during cerebral activation, whereas global CBF and global CMRglc both increased by 12%, reducing the molar ratio of oxygen to glucose consumption from 6.0 during baseline conditions to 5.4 during activation. Data obtained in the period following cerebral activation showed that the activation-induced resetting of the relation between CMRglc and CMRO2 persisted virtually unaltered for > or = 40 min after the mental activation task was terminated. The activation-induced increase in cerebral lactate efflux measured over the same time period accounted for only a small fraction of the activation-induced excess glucose uptake. These data confirm earlier reports that brain activation can induce resetting of the cerebral oxygen/glucose consumption ratio, and indicate that the resetting persists for a long period after cerebral activation has been terminated and physiologic stress indicators returned to baseline values. Activation-induced resetting of the cerebral oxygen/glucose uptake ratio is not necessarily accounted for by increased lactate production from nonoxidative glucose metabolism.

Adult↗
PubMed1995

Dynamic exercise enhances regional cerebral artery mean flow velocity.

Dynamic exercise enhances regional cerebral artery mean flow velocity. J. Appl. Physiol. 78(1): 12-16, 1995.--Anterior (ACA) and middle (MCA) cerebral artery mean flow velocities (Vmean) and pulsatility indexes were determined using transcranial Doppler in 14 subjects during dynamic exercise after assessment of the carbon dioxide reactivity for both arteries. Right hand contractions provoked an elevation in left MCA Vmean [19% (12-28); P < 0.01], whereas the pulsatility decreased in all four arteries (P < 0.05). During right foot movement, left ACA Vmean increased by 23% (11-37; P < 0.01) with lesser (approximately 10%; P < 0.05) increases in the other arteries, and pulsatility index decreased (P < 0.05). During cycling, ACA and MCA Vmean increased bilaterally by 23% (10-49) and 18% (5-32), respectively (P < 0.01), and the pulsatility was also elevated (P < 0.05). Cerebral artery pulsatility did not demonstrate a focal response but depended did not demonstrate a focal response but depended on the muscle mass involved during exercise. The data demonstrate a significant increase in Vmean for the artery supplying the cortical projection of the exercising limb. Insignificant and marginally significant increases in Vmean may be related to sympathetically mediated vasoconstriction and/or coactivation of untargeted muscle groups.

Adult↗
PubMed1995

Role of extracellular and intracellular acidosis for hypercapnia-induced inhibition of tension of isolated rat cerebral arteries.

The importance of smooth muscle cell pHi and pHo for the hypercapnic vasodilation of rat cerebral arteries was evaluated in vitro. Vessel segments were mounted in a myograph for isometric tension recording; pHi was measured by loading the smooth muscle cells with the fluorescent dye BCECF, and pHo was measured with a glass electrode. In all studies, Ca(2+)-dependent basal tension (in the absence of any agonist) and tension in the presence of arginine vasopressin were investigated. Control solution was physiological saline bubbled with 5% CO2 and containing 25 mmol/L HCO3- (pH 7.45 to 7.50). Induction of hypercapnic acidosis (10% CO2) or normocapnic acidosis (15 mmol/L HCO3-) caused significant inhibition of smooth muscle tension, and both conditions reduced pHi as well as pHo. N-Nitro-L-arginine significantly inhibited the relaxation to hypercapnic acidosis but had no significant effect on relaxation to normocapnic acidosis. Predominant extracellular acidosis, induced by reducing [HCO3-] from 25 to 9 mmol/L and CO2 from 5% to 2.5%, also caused inhibition of tension in steady state. By contrast, predominant intracellular acidosis, induced by increasing [HCO3-] from 25 to 65 mmol/L and CO2 from 5% to 15%, induced a small increase of basal tension and a small decrease of tension in the presence of arginine vasopressin. The responses to predominant intracellular or extracellular acidosis were qualitatively similar in the presence and absence of endothelium and in the presence and absence of N-nitro-L-arginine. It is concluded that the extracellular acidosis and not smooth muscle intracellular acidosis is responsible for the relaxation to hypercapnic acidosis.

Acidosis↗
PubMed1994

Nitric oxide (NO) is an endogenous anticonvulsant but not a mediator of the increase in cerebral blood flow accompanying bicuculline-induced seizures in rats.

Neurons synthesize NO, which may act as a retrograde messenger, involved in either potentiating or depressing neuronal excitability. NO may also play a role in the cerebral vasodilatory response to increased neuronal activity (i.e., seizures). In this study, two questions were asked: (1) is NO an endogenous anticonvulsant or proconvulsant substance? and (2) is the cerebral blood flow (CBF) increase accompanying bicuculline (BC)-induced seizures mediated by NO? The experiments were performed in 300-400-g Wistar rats anesthetized with 0.6% halothane and 70% N2O/30% O2. CBF was measured using the intracarotid 133Xe clearance method or laser-Doppler flowmetry. EEG activity was recorded. Chronic treatment (4 days) with nitro-L-arginine (L-NA), a potent NO synthase (NOS) inhibitor (400 mg/kg total), suppressed brain NOS by > 97% and prolonged seizure duration from 6 +/- 1 (saline-treated controls) to 12 +/- 2 min. In the L-NA-treated group, the CBF increase was sustained as long as seizure activity remained, indicating that CBF was still tightly coupled to seizure activity. Interestingly, the supposed inactive enantiomer of L-NA, D-NA, also showed an inhibition of brain NOS activity, ranging from 87 to 100%. The duration of seizures in this group (average 8 +/- 2 min) corresponded directly to the magnitude of reduction in NOS activity (r = 0.83, P < 0.05). Specifically, the D-NA results indicated that NOS inhibition had to exceed 95% before any effect on seizure duration could be seen.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Oxidoreductases↗
PubMed1994

Comparison of the effects of NG-nitro-L-arginine and indomethacin on the hypercapnic cerebral blood flow increase in rats.

The effects of NG-nitro-L-arginine (NOLAG), an inhibitor of nitric oxide synthase (NOS), and of indomethacin, an inhibitor of cyclooxygenase, on the rise in cerebral blood flow (CBF) accompanying increasing levels of hypercapnia (paCO2 = 40-135 mmHg) were studied in anesthetized rats. CBF was measured by intracarotid injection of 133Xe. Progressive increases in paCO2 of 10 mmHg, at intervals of about 8-10 minutes, were associated with gradual increases in CBF until a paCO2 level of 115 mmHg was reached. No further CBF changes (from the maximum value of 446 +/- 70 ml 100 g-1 min-1) were seen with additional step increase in paCO2. Intracarotid infusion of 7.5 mg/kg NOLAG significantly attenuated the CO2-elicited CBF increase by about 45-65% at paCO2 values below 115 mmHg. Beyond this level, there was a lesser inhibition of about 27-35%. 30 mg/kg NOLAG had essentially the same effect as 7.5 mg/kg NOLAG. 50 mg/kg NOLAG, given intraperitoneally (i.p.) twice daily for 4 days, also caused an attenuated CBF response to CO2, but the inhibitory effect was significantly less than with acute NOLAG administration in the paCO2 range of 61-90 mmHg. Infusion of L-arginine, 1 g/kg/h, prevented the effect of 7.5 mg/kg NOLAG. Indomethacin, 10 mg/kg, i.v. produced a more dramatic attenuation of the response, to the extent that the steady rising curve of CBF as a function of paCO2 was almost completely abolished. With indomethacin, a moderate increase (50%) in CBF was seen at the lowest level of hypercapnia, but raising paCO2 above this level did not result in further increases in CBF. This effect could not be prevented by L-arginine. When combining 7.5 mg/kg NOLAG with 10 mg/kg indomethacin, the response to hypercapnia was totally blocked. The results suggest that NOLAG and indomethacin act through different mechanisms on the hypercapnic CBF response, and that indomethacin is the more powerful inhibitor.

Animals↗
PubMed1994

Regional cerebral blood flow distribution in newly diagnosed schizophrenia and schizophreniform disorder.

Regional cerebral blood flow distribution (rCBF) in 24 first admissions with schizophrenia or schizophreniform disorder and in 17 healthy volunteers was examined. Single photon emission computed tomography with a brain-retained tracer, technetium-99m-d,l-hexamethyl-propylene amine oxime, was used to study subjects under resting conditions and during performance of the Wisconsin Card Sorting Test. The study is a replication of a previous investigation in an independent series of patients and healthy volunteers. The patients had significantly lower relative blood flow in prefrontal regions during activation than did the healthy volunteers. An earlier series of 19 patients and 7 healthy volunteers was studied using exactly the same procedure. Analyses of the combined samples from the two studies (43 patients and 24 healthy volunteers) showed the patients to have significantly lower relative flow in prefrontal regions both at rest and during activation and higher flow in the left striatum during activation. The same finding emerged when analyses were confined to drug-naive patients and patients educationally matched to the healthy volunteers. The study suggests a defective frontostriatal interrelationship in schizophrenia and schizophreniform disorder.

Adolescent↗
PubMed1994

Nitric oxide synthase inhibition and cerebrovascular regulation.

There is increasing evidence that nitric oxide (NO) is an important molecular messenger involved in a wide variety of biological processes. Recent data suggest that NO is also involved in the regulation of the cerebral circulation. Thus, NO participants in the maintenance of resting cerebrovascular tone and may play an important role in selected vasodilator responses of the cerebral circulation. Furthermore, evidence has been presented suggesting that NO participates in the mechanisms of cerebral ischemic damage. Despite the widespread attention that NO has captured in recent years and the large number of studies that have been published on the subject, there is considerable controversy regarding the role of this agent in cerebrovascular regulation and in ischemic damage. In this paper the results of investigations on NO and the cerebral circulation are reviewed and the evidence for and against a role of NO is critically examined.

Amino Acid Oxidoreductases↗
PubMed1994

Hypercapnic vasodilatation in isolated rat basilar arteries is exerted via low pH and does not involve nitric oxide synthase stimulation or cyclic GMP production.

The relaxant effect of hypercapnia (15% CO2) was studied in isolated circular segments of rat basilar arteries with intact endothelium. The nitric oxide synthase inhibitor nitro-L-arginine (L-NOARG) and the cytosolic guanylate cyclase inhibitor methylene blue (MB), significantly reduced this relaxation by 54% and 70%, respectively. The effect of L-NOARG was completely reversed by L-arginine. Blockade of nerve excitation with tetrodotoxin (TTX) had no affect on the 15% CO2 elicited vasodilatation. Measurements of cGMP in vessel segments showed no significant increase in cGMP content in response to hypercapnia. L-NOARG and MB, but not TTX, significantly reduced the basal cGMP content in cerebral vessels. Adding 1.5% halothane to the incubation medium did not result in a significant increase in cGMP content. Lowering the pH by cumulative application of 0.12 M HCl resulted in relaxation identical to that obtained by lowering the pH with 15% CO2. In vessel segments in which the endothelium had been removed beforehand 15% CO2 induced relaxation that was not different from that seen in vessels with intact endothelium. L-NOARG had no affect in endothelium denuded vessels. The results suggest that high CO2 elicits vasodilatation of isolated rat basilar arteries by a mechanism independent of nitric oxide synthase (NOS) activity. The markedly reduced basal cGMP levels in cerebral vessels by L-NOARG and MB suggest that there exists a basal NO formation in the cerebral vessel wall.

Amino Acid Oxidoreductases↗
PubMed1994

White matter magnetic resonance hyperintensities in dementia of the Alzheimer type: morphological and regional cerebral blood flow correlates.

In a prospective MRI study the presence, appearance, volume, and regional cerebral blood flow (rCBF) correlates of periventricular hyperintensities (PVHs) and deep white matter hyperintensities (DWMHs) were examined in 18 patients with probable Alzheimer's disease and in 10 age matched healthy control subjects, all without major cerbrovascular risk factors. The 133Xe inhalation method and the [99mTc]-d,l-hexamethyl-propylene-amine-oxime (HMPAO) technique with single photon emission computed tomography (SPECT) were used to measure rCBF. Rating scores for PVHs were significantly higher in the Alzheimer's disease group (p < 0.01) and correlated significantly with the volume of ventricles (p < 0.05) and with systolic arterial blood pressure (p < 0.01), but not with rCBF. By contrast, there was no significant difference in the rating scores or volumes of DWMHs between the two groups, although three patients had extensive DWMH lesions in the central white matter. In the group of patients with Alzheimer's disease as a whole, the volume of DWMHs correlated well with rCBF in the hippocampal region ( r = -0.72; p < 0.001), but not with frontal, temporal, parietal, or occipital rCBF. Postmortem histopathology of extensive DWMH lesions in one patient with definite Alzheimer's disease showed a partial loss of myelin and astrocytic gliosis, but no ischaemic changes. It is concluded that DWMH lesions may be associated with reduced rCBF in the hippocampal region. The heterogenous topography of neocortical rCBF deficits in Alzheimer's disease could not be explained by deafferentation from underlying white matter hyperintensities and therefore may reflect variations in the topography of cortical abnormalities.

Aged↗
PubMed1994

Heterogeneity of neocortical cerebral blood flow deficits in dementia of the Alzheimer type: a [99mTc]-d,l-HMPAO SPECT study.

Regional cerebral blood flow (rCBF) was measured with high resolution brain dedicated single photon emission computer tomography (SPECT) and [99mTc]-d,l-hexamethyl-propylene-amine-oxime (HMPAO) in 25 patients with probable Alzheimer's disease and in 25 control subjects, selected according to rigorous inclusion and exclusion criteria. The aim was to analyse the topography of rCBF deficits in individual patients. In the group of patients with Alzheimer's disease as a whole, global CBF was reduced, but a factorial analysis of variance did not show disproportionate reduction of rCBF in any brain region. A parametric analysis of the rCBF data in individual patients was carried out with reference to normal values for internal rCBF ratios and to 13 different abnormal rCBF patterns. These theoretical patterns were predefined by showing significant hypoperfusion in at least one, or in any relevant combination of two, three, or four, of four major brain regions (a left and right frontal and a left and right posterior region). All patients with Alzheimer's disease and none of the control subjects had an abnormal rCBF pattern. Eleven of the 13 different patterns were seen in the patients. Frontal changes were seen in 19 (76%) of the patients, more often than previously reported. No single Alzheimer's disease pattern could be derived from our data. The number of regions with hypoperfusion, but not the presence of frontal changes, correlated significantly with the duration of disease. It is concluded that a clinical diagnosis of probable Alzheimer's disease is associated with heterogeneous patterns of rCBF deficits as measured with SPECT and [99mTc]-d,l-HMPAO. This heterogeneity may reflect different stages of the disease or cognitive subtypes and help explain published discrepancies concerning the topography of hypoperfusion in Alzheimer's disease. An analysis of individual rCBF data may add important information in the investigation of diseases with heterogeneous effects on the brain.

Adult↗
PubMed1994

Cerebral oxygen extraction, oxygen consumption, and regional cerebral blood flow during the aura phase of migraine.

BACKGROUND AND PURPOSE: The aura phase of migraine is associated with focal blood flow changes, but it has been largely unknown whether these changes are correlated to changes in the cerebral metabolism. METHODS: Eight patients required carotid angiography for evaluation of transient neurological attacks. Cerebral blood flow (CBF) results, angiography, and clinical observations subsequently suggested the diagnosis: migraine with aura and occasional aura attacks without headache. In the same setting the cerebral angiography was followed by four to six repeated recordings of regional CBF using the intra-arterial 133Xe injection method. Blood samples were drawn from the carotid artery and the internal jugular vein to measure oxygen extraction fraction and cerebral metabolic rate for oxygen. RESULTS: The intracarotid regional CBF technique provoked aura symptoms and typical, migraine-related, posterior focal hypoperfusion in four patients, followed by typical unilateral headache in three patients. The remaining four patients had no symptoms or regional CBF changes during the examination. There was a significant increase (mean, 13%) of global oxygen extraction fraction in the four patients during aura symptoms, whereas no significant changes of oxygen extraction fraction were found in the nonsymptomatic group. The increase in global oxygen extraction fraction in the symptomatic group coincided with a drop of hemispheric CBF (mean, 12%). Cerebral metabolic oxygen rate remained essentially unchanged, as did PaCO2. CONCLUSIONS: The data presented suggest that the focal flow reduction during the migraine-aura phase is not a secondary phenomenon of reduced cerebral metabolism. However, arteriolar vasoconstriction might offer a possible explanation for the regional CBF changes observed during the migraine aura.

Adult↗