Biomedical subjects

M E Raichle

Publications and source records attributed to M E Raichle.

At least 199 records · Page 11Linked to original sources

PubMed1976

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.

Brain↗

PubMed1976

Changes in cerebral blood volume and vascular mean transit time during induced cerebral seizures.

The relationship of the mean transit time of the vascular indicator C15O-labeled hemoglobin (tco) and the cerebral blood volume (CBV) as measured by stimulated x-ray fluorescence, to the mean arterial blood pressure (MABP) was examined in rhesus monkeys before and during experiment cerebral seizures. The results demonstrate a marked increase in CBV and a decrease in tco. A substantial portion of these changes is the passive accompaniment of the associated increase in MABP.

Animals↗

PubMed1976

Blood-brain barrier permeability of 11C-labeled alcohols and 15O-labeled water.

The extraction of 11C-labeled methanol, ethanol, and isopropanol, as well as 15O-labeled water by the brain during a single capillary transit, was studied in vivo in six adult rhesus monkeys by external detection of the time course of these tracers subsequent to their internal carotid artery injection. The data demonstrate the feasibility of accurately measuring brain permeability of highly diffusible substances by this technique and show that neither water nor the alcohols studied freely equilibrate with brain when the cerebral blood flow exceeds 30 ml/100 g min-1. At a cerebral blood flow of 50 ml/100 g min-1 only about 93% of an injected bolus of labeled water freely exchanges with brain, compared with methanol (93%), ethanol (97%), and isopropanol (99%). The brain capillary permeability-surface area (PS) products computed from these data were 0.023 cm3/s g-1 (water), 0.024 cm3/s g-1 (methanol), 0.030 cm3/s g-1 (ethanol), and 0.062 cm3/s g-1 (isopropanol). This sequence of PS products is consistent with the individual lipid solubilities of the alcohols studied and underscores the unique brain permeability characteristics of lipid-insoluble water.

Alcohols↗

PubMed1976

Measurement of brain oxygen utilization with radioactive oxygen-15: experimental verification.

This study was designed to provide direct experimental evidence in support of the method employing radioactive 15O-tagged hemoglobin for the in vivo and regional measurement of the cerebral oxygen utilization rate (CMRO2). This was accomplished by simultaneously measuring in vivo the mean CMRO2 in monkeys and human beings by the 15O method and a direct appeal to the Fick principle using measured arteriovenous oxygen differences of brain. The correlation between the 2 methods was excellent, with a correlation coefficient of 0.90 (P less than 0.001) in monkeys and 0.88 (P less than 0.001) in human beings.

Animals↗

PubMed1976

Tomographic images of blood pool and perfusion in brain and heart.

A whole-body positron-emission transaxial tomograph (PETT III) was used to image the cross-sectional distribution of 13NH3 and 11CO-hemoglobin in the human brain and heart. Carotid and intravenous bolus injections of 13NH3 in the rhesus monkey had shown that 13NH3 is efficiently extracted by the brain and clears from it slowly (half-time, 40-50 min for carotid injections and 60-70 min for intravenous injections). The intravenous tomographic images in humans showed an excellent relationship between 13NH3 uptakes in the cortex, subcortical white matter, cerebellum, and brain stem and normal blood perfusion or flow in these structures. Cerebral lesions with high (metastasis) and low (stroke) blood flows showed correspondingly high and low uptakes of 13NH3. Large- and small-vascular structures of the brain were also clearly seen in 11CO-hemoglobin tomographic images. Normal myocardium and the ventricular chambers were well defined, and a transmural anterior myocardial infarct was clearly shown. The effective combination of positron transaxial tomography and compounds labeled with positron-emitters provides a safe new method for quantitatively imaging hemodynamic and physiologic functions of selected organs with good tomographic image quality.

Animals↗

PubMed1975

Cerebral blood flow and metabolism.

To date, regional measurements of cerebral blood flow in humans have not been especially helpful in predicting the outcome of acute brain injury. The recent appearance within the medical environment of biologically significant pharmaceuticals labelled with the positron-emitting isotopes 15O, 13N and 11C has made possible the quantitative regional measurement of cerebral metabolism in humans. This advance, coupled with the development of radically new detection systems, will allow the safe measurement of truly regional blood flow and metabolism in humans in the near future. Such information is basic to an understanding of the pathophysiology of acute injury to the brain and the rational prediction of outcome in the individual case.

Brain↗

PubMed1975

Central noradrenergic regulation of cerebral blood flow and vascular permeability.

Anatomical studies employing the immunofluorescence localization of dopamine-beta-hydroxylase [= dopamine beta-monooxygenase; 3,4-dihydroxyphenylethylamine, ascorbate:oxygen oxidoreductase (beta-hydroxylating); EC 1.14.17.1] have demonstrated in brain central noradrenergic nerve fibers on small intraparenchymal blood vessels, including capillaries. This system is distinct from the peripheral noradrenergic system inervating the large extraparenchymal blood vessels. From these anatomical findings evolved the working hypothesis that the central noradrenergic system is analogous to the peripheral sympathetic system except that it is specialized for performing specific functions related to the brain microvasculature. To test this hypothesis cerebral blood flow and the brain vascular permeability of water (H215O) were measured in four adult rhesus monkeys (three with bilateral superior cervical ganglionectomies) with stereotaxically placed cannulae permanently located in the lateral ventricles and the locus coeruleus for the injection of drugs. Our data demonstrate that stimulation of the noradrenergic cell bodies in the locus coeruleus with carbachol (8 mug) produces a prompt reduction in hemispheric cerebral blood flow and an increase in brain vascular permeability of water. The intraventricular administration of the alpha-adrenergic blocker phentolamine (25--50 mug) has the opposite effect. These preliminary data support the hypothesis that the central noradrenergic system is analogous to the peripheral sympathetic system with the special function of regulating brain vascular permeability as well as blood flow.

Animals↗

PubMed1975

In vivo measurement of brain glucose transport and metabolism employing glucose- -11C.

The radiopharmaceutical glucose--11C was used in vivo measurement of brain-glucose transport kinetics and metabolism in the rhesus monkey. Radiotracer was injected intravenously as a bolus. Radioactivity was continuously recorded from the head and from the arterial blood via an indwelling peripheral artery catheter for a collectionperiod of 2-3 min. To correct the reading obtained from the head for radioactivitycontained in blood, a second intravenous injection of the vascular tracer -15O-labeled carboxyhemoglobin was used. The method was tested in nine phencyclidine-anesthetized monkeys in which cerebral glucose metabolism (CMRGlc) was simultaneously measured by our method and by a standard method emplying the Fick principle. A highlysignificant correlation was found between the two methods of measuring CMRGlc (r =0.929). In addition, our model predicted a ratio of forward-to-reverse glucose flux across the blood-brain barrier (BBR) (1.37 plus or minus 0.23 SD), the brain-to-bloodglucose concentration ratio across the BBB (0.633 plus or minus 0.14), the relative tissue free-glucose space (17 plus or minus 7%), the brain free-glucose concentration (13.6plus or minus 8.5 mg/100 g of tissue), and the brain free-glucose turnover time (2.96 plus or minus 1.98 min). author

Animals↗

PubMed1975

In vivo determination of cerebral blood volume with radioactive oxygen-15 in the monkey.

A method for the in vivo determination of cerebral blood volume was tested in 15 adult rhesus monkeys. The technique utilized external residue detection and required the serial measurement of two mean transit times, namely, that of an intravascular tracer, C15O-hemoglobin, and that of a diffusible tracer, H215O. In computing the mean transit time for the intravascular tracer, the conventional Hamilton extrapolation of the downslope of the recording obtained for the washout of the tracer from the brain subsequent to an intracarotid bolus injection was found to be inadequate, yielding a mean transit time that systematically underestimated that parameter. Alternatively, the use of a power law extrapolation, as proposed by Huang, allowed a more accurate prediction of the vascular mean transit time. The preliminary studies testing the method predicted that the relationship between cerebral blood volume (CBV) and cerebral blood flow (CBF) was adequately represented by the equation CBV = 0.80CBF0.38, with a correlation coefficient of r = 0.90 for the cerebral blood flow range of 16 to 134 ml/100 g min-1 with a normocapnic cerebral blood volume of 3.5 ml/100 g perfused brain tissue (arterial Pco2 = 37 torr, CBF = 50 ml/100 g min-1).

Animals↗

PubMed1975

Effects of increased intracranial pressure on cerebral blood volume, blood flow, and oxygen utilization in monkeys.

The relationship of cerebral blood volume (CBV) to cerebral perfusion pressure (CPP), cerebral blood flow (CBF), and the cerebral metabolic rate for oxygen (CMRO2) was examined in rhesus monkeys. In vivo tracer methods employing radioactive oxygen-15 were used to measure CBV, CBF, and CMRO2. Cerebral perfusion pressure was decreased by raising the intracranial pressure (ICP) by infusion of artificial cerebrospinal fluid (CSF) into the cisterna magna. The production of progressive intracranial hypertension to an ICP of 70 torr (CPP of 40 torr) caused a rise in CBV accompanied by a steady CBF. With a further increase in ICP to 94 torr, CBV remained elevated without change while CBF declined significantly. Cerebral metabolic rate for oxygen did not change significantly during intracranial hypertension. For comparison, CPP was lowered by reducing mean arterial blood pressure in a second group of monkeys. Only CBF was measured in this group. In this second group of animals, the lower limit of CBF autoregulation was reached at a higher CPP (CPP approximately to 80 torr) than when an increase in ICP was employed (CPP approximately to 30 torr).

Animals↗

PubMed1975