No abstract

The blood-brain barrier (BBB) in man was studied during various conditions using the indicator dilution method of Crone [8]. Using 113m In-DTPA as reference substance the extraction, E, of the small test substances 24Na+, 36Cl-, 14C-urea and 14C-thiourea was estimated from the areas under the venous outflow curves following intracarotid slug injection of tracers. Interlaminar diffusion and red cell carriage were taken into consideration when calculating E. Cerebral blood flow (CBF) was measured using the intra-arterial 133Xe-injection method. Twenty-two patients receiving electroconvulsive therapy (ECT) were studied before and during seizures and during hypercapnia. Before seizures the extraction values in % were as follows: ENa+ 1.6, ECl- 1.9, Eurea 3.9 and Ethiourea 7.8; the corresponding values for the permeability-surface area products (PS) in ml/100 g x min were 0.5, 0.3, 0.7, 4.1, respectively. During seizure a decrease of Ethiourea and an increase of PSurea were significant. During hypercapnia PSNa and PSthiourea rose significantly. Due to the similarity of the findings in those two high flow situations it is suggested that the changes of CBF and not the epileptic activity are responsible for the changes in permeability. The mechanism of action may be a stretching of endothelial cells in the cerebral vessels or an opening up of new capillaries, or a combination of both.

Summary: Blood-brain barrier permeability to L-Iactate was studied in 18 patients with the double indicator tech nique. Venous outflow curves were obtained during normo-and hypercapnia and were analyzed by means of a model that takes tracer backflux and capillary hetero geneity of transit times into account. The average unidi rectional extraction of L-Iactate was 15%; the transport from the blood to the brain (PS I ) was 0.081 ml g -I min-I and the transport from the brain to the blood (PS 2 ) was on the same order of magnitude. In hypercapnia. arterial pH decreased from 7.39 to 7.26 and PS I to L-lactate increased Lactate is a key intermediate in brain ischemia, where it is produced at increased rates, and this may have deleterious effects upon the course of brain infarction. The transport of lactate across the blood-brain barrier (BBB) therefore becomes of major interest. Furthermore, in brain ischemia, tis sue pH and maybe also local plasma pH change, and this may effect the transfer rates. The transport kinetics across the BBB in humans has so far not been described. In rats, L-lactate has been shown to cross the BBB by means of facilitated diffusion me diated by a stereospecific monocarboxylic acid car rier (Nemoto and Severinghaus, 1971;Oldendorf, 1972). This carrier permits the escape of lactate from the brain, the brain normally exhibiting a small net efflux of lactate (Drewes et aI., 1973).The present study investigated the bidirectional transport across the human BBB of lactate and the influence of hypercapnia upon this transport.Received August 24, 1990; revised December 5, 1990; ac cepted December 7, 1990.Address correspondence and reprint requests to Dr. G. Moos Knudsen at Dept. of Neurol ogy, N2082, Rigshospital et, 9, Blegdamsvej, DK-2100 Copenhagen, Denmark.Abbreviations used: BBB, bl ood-brain barrier; BUl, brain up take index; DTPA, diethylenetnaminepentaacetic acid; ECS, ex tracel lular space; PS, permeabil ity-surface area product. 581significantly by 110%. PS 2 also increased although a sta tistically significant difference compared to the resting state was not reached. It is concluded that L-Iactate is easily taken up by the human brain, and that the mecha nism by which it crosses the blood-brain barrier is equil ibrative. Furthermore, the brain permeability to lactate is enhanced by hypercapnia and the mechanism is believed to act through the decrease in pH. Key Words: Blood brain barrier-Humans-Lactate-pH dependence Double indicator technique. MATERIALS AND METHODS PatientsEighteen patients (mean age of 46 ± 12 years, range of 24 to 71 years) hospitalized for various cerebral disorders requiring carotid angiograms were studied in connection with the angiography after informed consent had been obtained. The study was conducted in agreement with the local ethical committee. Patients with major cerebral le sions (e.g., larger tumors) that might interfere with BBB function were excluded.After percutaneous punctures in the neck under local anesthesia, using the Seldinger technique a small poly...

SUMMARY Using the "double indicator" technique the ability of 3 H-isoproterenol and "C-propranolol to cross the blood-brain barrier was studied in man. In 3 subjects extraction of isoproterenol was 3.8% in a single passage and the PS product was 2.0 ml/lOOg/min. In 4 patients extraction of propranolol was 63% and PS was 46.7 ml/100/min. Regional cerebral blood flow (rCBF) was studied in man with the 133 Xe-intraarterial injection method. Intracarotid isoproterenol (3 /xg/min., 6 patients) caused a significant reduction in rCBF, but after correction for a concomitant decrease in arterial Pco 2 the alteration was no longer significant (59.8 -51.7/57.4 ml/100g/min.). Intracarotid propranolol (0.15 mg/kg, 11 patients) caused no significant change in rCBF, but after correction for arterial Pco 2 change the alteration although only 4% was just significant,/? < 0.05. (56.3-55.8/54.1 ml/lOOg/min). After propranolol the rCBF changes caused by alterations in the arterial Pco 2 were normal and the focal flow increase during hand work could not be changed by simultaneous intracarotid propranolol.RECENT scientific investigations have dealt with the effects of cervical sympathetic nerve stimulation/section or with the pharmacology of the cerebrovascular a-adrenergic receptor mechanisms. This extensive literature is somewhat contradictory, but increasing evidence supports the contention that sympathetic nerves via a-receptors play a significant role in the tone of brain vessels under certain circumstances. For the most recent studies see Edvinsson and McKenzie.

Our findings elaborate on previous findings and are in line with recent neurological findings suggesting that disgust and insular impairments are associated with AN. Clinical implications of our findings are discussed.

A B S T R A C T Blood-brain barrier permeabilitv studies made in man using the indicator dilution method revealed that the extraction of the test substance increases during the upslope of the venous (outflow) dilution curve. The present study aimed to obviate the possibility that this could result from intravascular phenomena, such as interlaminar diffusion (the result of differences in molecular size) and erythrocyte carriage. Several reference substances were employed for the determination of the extraction in order that careful correction could be made for differences in intravascular behavior of the test and reference substance. The test substances studied were D-glucose, L-phenylalanine, water, propranolol, and benzodiazepines, representing both carrier-transported and lipophilic substances. In-diethylenetriamine pentaacetic acid, Na+, C1-, L-glucose, and L-lysine were employed as reference substances.For all the substances tested, and after correction for intravascular phenomena, the extractions were found to increase during the initial part of the dilution curve. This increasing extraction can be ascribed to heterogeneity of the cerebral circulation; the higher extraction corresponds to longer contact with the blood-brain barrier and indicates a longer transit time. Signs of heterogeneity were also present when blood flow was elevated above normal. Any influence that heterogeneity might have on the mean extraction value can be minimized by using an appropriate calculation of

No abstract

No abstract