Cerebral Blood Flow and Oxygen Consumption in the Rat in Hypoxic Hypoxia

In order to measure cerebral blood flow (CBF) and cerebral metabolic rate for oxygen (CMRo₂) at pronounced degrees of hypoxic hypoxia the Pao₂ of artificially ventilated and normocapnic rats was reduced to between 47 and 22 mm Hg for 15–25 min with subsequent measurements of CBF, using a ¹³³Xenon modification of the Kety and Schmidt technique, and of the arteriovenous difference in oxygen content, the venous blood being obtained from the superior sagittal sinus. When the Pao₂ was reduced to minimal values of 22 mm Hg CBF increased 4- to 6-fold, the increase in CBF being unrelated to changes in blood pressure or Paco₂. The CMRo₂ remained unchanged at all levels of hypoxia. It is concluded that the maintenance of a normal, or near-normal, cerebral energy state even at extreme degrees of hypoxic hypoxia depends solely on a homeostatic increase in CBF.     

A method for determining blood flow and oxygen consumption in the rat brain.

Cerebral blood flow (CBF) and cerebral metabolic rate for oxygen (CMRo2) were measured in rats under nitrous oxide anaesthesia, using a 133Xenon modification of the Kety and Schmidt inert gas technique with sampling of cerebral venous blood from the retroglenoid vein. Extracerebral contamination of the venous blood sampled was studied by comparing the rates at which the activity of 133Xenon decreased in blood and tissues. Contamination was avoided by gentle compression of the contralateral retroglenoid vein during sampling. CBF and CMRo2 of the rat brain were 80+/-2 and 7.6+/-0.2 ml-(100g)-1-min-1, respectively. These values are about 25% lower than those previously obtained for cerebral cortical tissue under similar conditions. Induced hypercapnia (Paco2 about 70 mm Hg) or hypocapnia (Paco2 15-20 mm Hg) gave rise to expected changes in CBF but did not alter CMRo2. The CMRo2 of the rat brain is at least twice that of the human brain. This species difference, which is similar to that previously reported for the oxygen uptake of cerebral tissue in vitro, probably reflects on inverse relationship between brain weight and neuronal packing density.     

Influence of intravenously administered catecholamines on cerebral oxygen consumption and blood flow in the rat

In order to study effects of catecholamines on cerebral oxygen consumption (CMRo₂) and blood flow (CBF), rats maintained on 75 % N₂O and 25 % O₂, were infused i.v. with noradrenaline (2, 5, or 8 μpg. kg^-1. min^-1) or adrenaline (2 or 8, μg. kg^-1.min^-1) for 10 min before CBF and CMR_oz were measured. In about 50% of animals infused with 2–8, μg. kg^-1 min^-1 of noradrenaline, CMRo_z (and CBF) rose. However, there was no dose-dependent response, and CMRo₂, did not exceed 150% of control. The effects of noradrenaline in a dose of 5 μg. kg^-l. min^-1 on CMRo₂, and CBF were blocked by propranolol (2.5μg.kg^-1). In animals infused with adrenaline (8 μg.kg^-1.min^-1) CMRo₂, was doubled and, in many, CBF rose 4- to 6-fold. It is concluded that, when given in sufficient amounts, catecholamines have pronounced effects on cerebral metabolism and blood flow, the effects of adrenaline on CMRo₂, and CBF resembling those observed in status epilepticus.     

The Kety–Schmidt technique for repeated measurements of global cerebral blood flow and metabolism in the conscious rat

Cerebral activation will increase cerebral blood flow (CBF) and cerebral glucose uptake (CMR_glc) more than it increases cerebral uptake of oxygen (CMR_O2). To study this phenomenon, we present an application of the Kety–Schmidt technique that enables repetitive simultaneous determination of CBF, CMR_O2, CMR_glc and CMR_lac on awake, non-stressed animals. After constant intravenous infusion with ¹³³Xenon, tracer infusion is terminated, and systemic arterial blood and cerebral venous blood are continuously withdrawn for 9 min. In this paper, we evaluate if the assumptions applied with the Kety–Schmidt technique are fulfilled with our application of the method. When measured twice in the same animal, the intra-individual variation for CBF, CMR_O2, and CMR_glc were 10% (SD: 25%), 8% (SD: 25%), and 9% (SD: 28%), respectively. In the awake rat the values obtained for CBF, CMR_O2 and CMR_glc were 106 mL [100 g]^?1 min^?1, 374 μmole [100 g]^?1 min^?1 and 66 μmole [100 g]^?1 min^?1, respectively. The glucose taken up by the brain during wakefulness was fully accounted for by oxidation and cerebral lactate efflux. Anaesthesia with pentobarbital induced a uniform reduction of cerebral blood flow and metabolism by ≈40%. During halothane anaesthesia CBF and CMR_glc increased by ≈50%, while CMR_O2 was unchanged.     

The effect of propranolol on cerebral oxygen consumption and blood flow in the rat: measurements during normocapnia and hypercapnia

The cerebral blood flow (CBF) and cerebral oxygen consumption (CMRO,) in the rat during normocapnia and hypercapnia were investigated by means of the intraarterial ¹³³Xenon injection technique; measurements were performed during normocapnia and hypercapnia and the effect of propranolol upon CBF and CMRO₂ was studied. The CBF technique applied to rat yield reliable results even in high flow situations. A steady state period of only 10–15 s is all that is necessary to obtain the initial slope of the ¹³³Xenon clearance curve from which CBF is calculated and measurements may be repeated within minutes. Hypercapnia caused an increase in CMRO₂ of 35% which confirms the findings of other investigators. The beta-adrenergic receptor blocker propranolol (2 rag per kg i.v.) prevented this increase and could eliminate an increase in CMRO₂ already induced; this indicates that CO₂ affects adrenergic mechanisms. Although propranolol eliminated the CMRO₂ response to hypercapnia, it only reduced the CBF response; this dissociation of CBF and CMRO₂ response occurred probably because the beta-receptor blockage only eliminated a CBF increase mediated through an increased CMRO₂ (cellular response) whereas a direct CO₂ effect upon the arterioles (vascular response) persisted.     

Cerebral blood flow and oxygen consumption in the rat in hypoxic hypoxia.

In order to measure cerebral blood flow (CBF) and cerebral metabolic rate for oxygen (CMRo(2)) at pronounced degrees of hypoxic hypoxia the Pao(2) of artificially ventilated and normocapnic rats was reduced to between 47 and 22 mm Hg for 15-25 min with subsequent measurements of CBF, using a -133Xenon modification of the Kety and Schmidt technique, and of the arteriovenous difference in oxygen content, the venous blood being obtained from the superior sagittal sinus. When the Pao(2) was reduced to minimal values of 22 mm Hg CBF increased 4- to 6-fold, the increase in CBF being unrelated to changes in blood pressure or Paco(2). The CMRo(2) remained unchanged at all levels of hypoxia. It is concluded that the maintenance of a normal, or near-normal, cerebral energy state even at extreme degrees of hypoxic hypoxia depends solely on a homeostatic increase in CBF.     

The Relationship between Arterial PO2 and Cerebral Blood Flow in Hypoxic Hypoxia

The relationship between arterial oxygen tension (Pa_O2) and cerebral blood flow (CBF) in hypoxic hypoxia was studied in artificially ventilated and normocapnic rats. Changes in CBF were evaluated from arterio-venous differences in oxygen content after 2, 5, 15 and 30 min exposure to Pa_O2 85, 75, 55, 45, 35 and 25 mm Hg. In separate experiments the Pa_O2 was decreased to 25 mm Hg for 1, 2, 5, 15 and 30 min in animals in which Pa_CO2 was allowed to fall by 5–10 mm Hg. There was a small, gradual increase in CBF when Pao, was lowered in steps from 130 to 55 mm Hg, and a more pronounced increase at P_O2 values below 50 mm Hg. At Pa_O2 25 mm Hg CBF increased to values of 500% of normal. Significant increases in CBF were recorded at Pa_O2 values of 85 and 75 mm Hg in spite of the fact that previous studies have failed to record an elevatad tissue lactate content at these P_O2 levels, and in spite of an unchanged cerebral venous P_O2. When the Pa_O2 was reduced to 25 mm Hg CBF increased markedly already at 1 and 2 min, and this increase in CBF occurred even if Pa_CO2 was allowed to fall by 5–10 mm Hg. Previous results have shown that in such short periods enough lactic acid is not formed to induce a net tissue acidosis. The results thus give no support to the hypothesis that cerebral hyperemia in hypoxia is coupled to accumulation of lactic acid in the tissue.     

BOLD‐specific cerebral blood volume and blood flow changes during neuronal activation in humans

To understand and predict the blood‐oxygenation level‐dependent (BOLD) fMRI signal, an accurate knowledge of the relationship between cerebral blood flow (ΔCBF) and volume (ΔCBV) changes is critical. Currently, this relationship is widely assumed to be characterized by Grubb's power‐law, derived from primate data, where the power coefficient (α) was found to be 0.38. The validity of this general formulation has been examined previously, and an α of 0.38 has been frequently cited when calculating the cerebral oxygen metabolism change (ΔCMRo₂) using calibrated BOLD. However, the direct use of this relationship has been the subject of some debate, since it is well established that the BOLD signal is primarily modulated by changes in ‘venous’ CBV (ΔCBV_v, comprising deoxygenated blood in the capillary, venular, and to a lesser extent, in the arteriolar compartments) instead of total CBV, and yet ΔCBV_v measurements in humans have been extremely scarce. In this work, we demonstrate reproducible ΔCBV_v measurements at 3 T using venous refocusing for the volume estimation (VERVE) technique, and report on steady‐state ΔCBV_v and ΔCBF measurements in human subjects undergoing graded visual and sensorimotor stimulation. We found that: (1) a BOLD‐specific flow‐volume power‐law relationship is described by α = 0.23 ± 0.05, significantly lower than Grubb's constant of 0.38 for total CBV; (2) this power‐law constant was not found to vary significantly between the visual and sensorimotor areas; and (3) the use of Grubb's value of 0.38 in gradient‐echo BOLD modeling results in an underestimation of ΔCMRo₂. Copyright © 2009 John Wiley & Sons, Ltd.     

The intracarotid 133xenon injection method for measurement of cerebral blood flow (CBF) in rats: evaluation of the effect of bolus volume

It is assumed that the cerebral microcirculation is not perturbed by the intraarterial injection used in determination of cerebral blood flow (CBF) with the intraarterial 133Xenon technique (and in various assessments of blood brain barrier (BBB) permeability). The application of these techniques to the rat, where the injectate is large compared to normal blood flow, places this problem is focus and it has been claimed that since large intracarotid injections increased cerebral venous outflow, the CBF must also increase. We investigated this problem in the rat by means of the intraarterial 133Xenon injection technique, using a saline bolus injected in less than 1 sec and found that CBF was unaltered at bolus volumes between 10 and 100 microliters. Furthermore, injection of 100-200 microliters saline during washout detection did not change the slope of the semilogarithmic wash-put curves. It is concluded that in spite of large intracarotid injections the CBF remained constant and that the hemodilution produced by the saline bolus is not sufficient to influence CBF. Consequently, estimations of CBF yield valid results in the present rat preparation.     

Postischemic Cerebral Blood Flow and Oxygen Utilization Rate in Rats Anesthetized with Nitrous Oxide or Phenobarbital

The present experiments were undertaken to measure postischemic regional cerebral blood flow (rCBF) and oxygen utilization rate (CMRo₂) in rats anesthetized with either 70 % N₂O or phenobarbital (150 mg × kg^-1). In previous studies we have found that extensive restitution of cerebral energy metabolites occurs after 30 min of complete cerebral ischemia irrespective of the type of anesthesia used. Following 30 min of pronounced, incomplete ischemia, however, a comparable restitution of cerebral energy state was obtained in deeply anesthetized (phenobarbital 150 mg × kg^-1) but not in superficially anesthetized (70% N₂O) rats. The objectives of the present investigation were (1) to study whether postischemic cerebral blood flow was higher in barbiturate-anesthetized animals during the initial recirculation period, and (2) to investigate if the protective effects of phenobarbital previously observed could be attributed to a decrease in CMRo₂. In both groups of animals a considerable variability in postischemic rCBF was observed between different animals. However, no signs of gross inhomogeneity in blood flow were found and no consistent differences in flow values between the two groups of animals were observed. Since the measured postischemic CMRo, were identical in both groups of animals and since cerebral venous oxygen contents were above normal the results leave little support to the assumption that, in the present model of transient, incomplete cerebral ischemia, failure of recovery of cerebral metabolism (N₂O group) is primarily due to impaired recirculation, nor do they indicate that the protective effects of barbiturates is due to their ability to reduce rate of cerebral energy utilization.     

Cerebral oxygenation is reduced during hyperthermic exercise in humans

Aim: Cerebral mitochondrial oxygen tension (P_mitoO₂) is elevated during moderate exercise, while it is reduced when exercise becomes strenuous, reflecting an elevated cerebral metabolic rate for oxygen (CMRO₂) combined with hyperventilation-induced attenuation of cerebral blood flow (CBF). Heat stress challenges exercise capacity as expressed by increased rating of perceived exertion (RPE). Methods: This study evaluated the effect of heat stress during exercise on P_mitoO₂ calculated based on a Kety-Schmidt-determined CBF and the arterial-to-jugular venous oxygen differences in eight males [27 ± 6 years (mean ± SD) and maximal oxygen uptake (VO_2max) 63 ± 6 mL kg⁻¹ min⁻¹]. Results: The CBF, CMRO₂ and P_mitoO₂ remained stable during 1 h of moderate cycling (170 ± 11 W, ∼50% of VO_2max, RPE 9–12) in normothermia (core temperature of 37.8 ± 0.4 °C). In contrast, when hyperthermia was provoked by dressing the subjects in watertight clothing during exercise (core temperature 39.5 ± 0.2 °C), P_mitoO₂ declined by 4.8 ± 3.8 mmHg (P < 0.05 compared to normothermia) because CMRO₂ increased by 8 ± 7% at the same time as CBF was reduced by 15 ± 13% (P < 0.05). During exercise with heat stress, RPE increased to 19 (19–20; P < 0.05); the RPE correlated inversely with P_mitoO₂ (r² = 0.42, P < 0.05). Conclusion: These data indicate that strenuous exercise in the heat lowers cerebral P_mitoO₂, and that exercise capacity in this condition may be dependent on maintained cerebral oxygenation.     

Whole-brain blood flow and oxygen metabolism in the rat during nitrous oxide anesthesia.

The Kety-Schmidt washout technique has been modified to measure whole-brain blood flow and metabolism in the rat. During nitrous oxide anesthesia, 14 rats exhaled (133)Xe, and continuous and simultaneous arterial and cerebral venous samples were drawn from a femoral artery and the transverse sinus of the brain. Extracerebral contamination of the venous sample was minimal, and equilibration of (133)Xe in brain tissue and blood was obtained after 10-24 min of inhalation. Cerebral blood flow was calculated from the total activity of the mechanically integrated arterial and venous samples according to the principle of Scheinberg and Stead. At a mean Paco2 of 40 mmHg, CBF averaged 98 +/- 6 (SEM) ml/100 g-min and CMRO2 averaged 5.4 +/- 0.7 (SEM) ml/100 g-min. CBF changed 2.4% with each millimeter Hg change of Paco2 while CMRO2 changed only insignificantly. The values obtained for CBF are higher than reported for man and large laboratory animals bur reflect the proportionately greater amount of gray matter in the rat brain.     

The relationship between arterial po2 and cerebral blood flow in hypoxic hypoxia.

The relationship between arterial oxygen tension (PaO2) and cerebral blood flow (CBF) in hypoxic hypoxia was studied in artificially ventilated and normocapnic rats. Changes in CBF were evaluated from arteriovenous differences in oxygen content after 2, 5, 15 and 30 min exposure to PaO2 85, 75, 55, 45, 35, and 25 mm Hg. In separate experiments the PaO2 was decreased to 25 mm Hg for 1, 2, 5, 15 and 30 min in animals in which PaCO2 was allowed to fall by 5-10 mm Hg. There was a small, gradual increase in CBF when PaO2 was lowered in steps from 130 to 55 mm Hg, and a more pronounced increase at PO2 values below 50 mm Hg. At PaO2 25 mm Hg CBF increased to values of 500% of normal. Significant increased in CBF were recorded at PaO2 values of 85 and 75 mm Hg in spite of the fact that previous studies have failed to record an elevated tissue lactate content at these po2 levels, and in spite of an unchanged cerebral venous PO2. When the PaO2 was reduced to 25 mm Hg CBF increased markedly already at 1 and 2 min, and this increase in CBF occurred even if PaCO2 was allowed to fall by 5-10 mm Hg. Previous results have shown that in such short periods enough lactic acid is not formed to induce a net tissue acidosis. The results thus give no support to the hypothesis that cerebral hyperemia in hypoxia is coupled to accumulation of lactic acid in the tissue.     

The Influence of Acute Normovolemic Anemia on Cerebral Blood Flow and Oxygen Consumption of Anesthetized Rats

The influence of acute normovolemic anemia on cerebral blood flow (CBF) and cerebral metabolic rate for oxygen (CMR_O2) was studied in normocapnic rats under nitrous oxide anaesthesia. The arterial hemoglobin content was reduced to values of about 12, 9, 6 and 3 g.(100 ml)^-1 by arterial bleeding and substitution with equal volumes of homologous plasma. The CBF increased in proportion to the reduction in hemoglobin content to reach values of 500–600 per cent of normal at extreme degrees of anemia, but CMR_O2 remained unchanged. Cerebral venous P_O2 and oxygen saturation did not decrease below normal values, indicating that tissue hypoxia did not develop. However, since the increase in CBF at hemoglobin concentrations of below 9 g ^. (100 ml)^-1 was far in excess of that expected from the decrease in viscosity the results indicate that dilatation of cerebral resistance vessels occurred. This dilatation, which was obviously related to the fall in arterial oxygen content, cannot be explained by any of the current theories proposed to explain cerebral hyperemia in hypoxia.     

The Kety-Schmidt technique for repeated measurements of global cerebral blood flow and metabolism in the conscious rat.

Cerebral activation will increase cerebral blood flow (CBF) and cerebral glucose uptake (CMRglc) more than it increases cerebral uptake of oxygen (CMR(O2)). To study this phenomenon, we present an application of the Kety-Schmidt technique that enables repetitive simultaneous determination of CBF, CMR(O2), CMRglc and CMRlac on awake, non-stressed animals. After constant intravenous infusion with 133Xenon, tracer infusion is terminated, and systemic arterial blood and cerebral venous blood are continuously withdrawn for 9 min. In this paper, we evaluate if the assumptions applied with the Kety-Schmidt technique are fulfilled with our application of the method. When measured twice in the same animal, the intra-individual variation for CBF, CMR(O2), and CMRglc were 10% (SD: 25%), 8% (SD: 25%), and 9% (SD: 28%), respectively. In the awake rat the values obtained for CBF, CMR(O2) and CMRglc were 106 mL [100 g](-1) min(-1), 374 micromole [100 g](-1) min(-1) and 66 micromole [100 g](-1) min(-1), respectively. The glucose taken up by the brain during wakefulness was fully accounted for by oxidation and cerebral lactate efflux. Anaesthesia with pentobarbital induced a uniform reduction of cerebral blood flow and metabolism by approximately 40%. During halothane anaesthesia CBF and CMRglc increased by approximately 50%, while CMR(O2) was unchanged.     

The effect of propranolol on cerebral oxygen consumption and blood flow in the rat: measurements during normocapnia and hypercapnia.

The cerebral blood flow (CBF) and cerebral oxygen consumption (CMRO2) in the rat during normocapnia and hypercapnia were investigated by means of the intraarterial 133Xenon injection technique; measurements were performed during normocapnia and hypercapnia and the effect of propranolol upon CBF and CMRO2 was studied. The CBF technique applied to rat yield reliable results even in high flow situations. A steady state period of only 10--15 s is all that is necessary to obtain the initial slope of the 133Xenon clearance curve from which CBF is calculated and measurements may be repeated within minutes. Hypercapnia caused an increase in CMRO2 of 35% which confirms the findings of other investigators. The beta-adrenergic receptor blocker propranolol (2 mg per kg i.v.) prevented this increase and could eliminate an increase in CMRO2 already induced; this indicates that CO2 affects adrenergic mechanisms. Although propranolol eliminated the CMRO2 response to hypercapnia, it only reduced the CBF response; this dissociation of CBF and CMRO2 response occurred probably because the beta-receptor blockage only eliminated a CBF increase mediated through an increased CMRO2 (cellular response) whereas a direct CO2 effect upon the arterioles (vascular response) persisted.     

Rapid measurement of regional cerebral blood flow in the baboon using15O-labelled water and dynamic positron emission tomography

The sensitivity and reproducibility of rapid measurements of regional cerebral flow (rCBF) using a bolus injection of H₂ ¹⁵O and dynamic positron emission tomography (PET) were investigated in anaesthetised baboons. The cerebrovascular reactivity to changes in arterial pCO₂ was used as an experimental support. PET data were acquired over 4 min following a single bolus intravenous injection of H₂ ¹⁵O, while arterial blood was withdrawn for continuous activity counting. Images were reconstructed with a dynamic sequence of 45×2s+15×10s, including a correction for decay. Regional values of CBF were derived from non-linear least-squares fits of the time activity curves using a four-parameter two-compartment model. The results obtained with a four-parameter fitting method were compared with those obtained with two other rapid estimation methods, first fitting two parameters only, CBF and partition coefficient (p), and secondly autoradiography (with p fixed at 0·95 ml brain ml blood⁻¹). Twelve regions of interest were analysed. The values for the basal CBF obtained from 13 measurements in two baboons were close to published values obtained with other techniques. Reproducibility checks showed a mean variation of 9·7 per cent. The CBF measurements performed in hypercapnic conditions gave results similar to published data in other animal species, showing a 4·5±0·9 per cent increase in CBF per mm Hg p_aCO₂. The results obtained with the three estimation techniques were closely correlated. The dynamic bolus H₂ ¹⁵O method appeared to be suitable for high blood flow measurements.     

Zum Einfluß des Ca-Antagonisten Nimodipin auf die globale und regionale Hirndurchblutung

Summary The effects of Nimodipine on the global and regional cerebral blood flow were studied in 42 patients with cerebrovascular disorders. In 25 patients with focal deficits such as transitory ischemic attack (TIA), prolonged reversible ischemic neurological deficit (PRIND), and minor stroke due to arteriosclerosis, and in eleven patients with cerebral vasospasm after subarachnoid hemorrhage, the cerebral blood flow was measured by¹³³Xenon inhalation technique 60 min after oral administration of 40, 60, or 80 mg Nimodipine. In 6 patients with vasospasm the effects of Nimodipine i.v. were examined. The result in twelve patients with minor stroke who were only given placebo (lactose; test-retest) was identical regional (rCBF) and global (CBF) cerebral blood flow before and 60 min after; placebo, blood pressure, and arterial pCO₂ remained constant as well. After Nimodipine, however, the CBF increases, the increase after vasospasm being significant when taking the pCO₂ in the Wilcoxon test into account. The rCBF increases much more in the regions with low perfusion rates than in well-perfused areas. This is also observed in the patients with TIA, PRIND, or minor stroke, most clearly after oral administration of 60 mg, whereas regions with normal perfusion rates show little reaction. The blood pressure was lowered, depending on the initial pressure. There was no evidence of a steal phenomenon.

---

Abkürzungen Ca Calcium - CBF Hirndurchblutung (cerebral blood flow) - F_G Durchblutung der grauen Hirnsubstanz - F_W Durchblutung der weißen Hirnsubstanz - ISI Initial slope Index (Auswertemethode der Hirndurchblutung bei Xenon-Clearance-Technik) - K auf - pCO₂ 40 mm Hg korrigierte CBF-Werte (in den Abbildungen) - PRIND prolonged reversible ischemic neurological deficit; vollständige klinische Rückbildung der Ausfallserscheinungen nach mehr als 24 h - rCBF regionale Hirndurchbltung - SAB Subarachnoidalblutung - TIA transitorische cerebralischämische Attacke (rasche vollständige Rückbildung der klinischen Symptome innerhalb 24 h) - UN deutlich (mindestens 10%) untermittelwertig durchblutete Hirnregion - ÜB deutlich (mindestens 10%) übermittelwertig durchblutete Hirnregion (in den Abbildungen) - U unkorrigierte gemessene Hirndurchblutungswerte (ohne pCO₂-Berücksichtigung in den Abbildungen)     

Measurement of regional blood flow by the 133xenon inhalation method with an on-line computer.

A computer based multidetector system was developed for the measurement of regional cerebral blood flow (rCBF) by the ¹³³Xenon inhalation technique. The computer portion of the system is characterized by on-line data acquisition, rapid data analysis and presentation of results. Special system features include programs which automatically determine end-tidal Xenon concentrations during the saturation and desaturation phases of the flow measurement and which provide for automatic background subtraction, and a special purpose counter-digital multiplexor-computer interface. The system provides convenience in handling acutely ill patients, and assures reproducible positioning for serial measurements. Typical output format and partial results from 150 patient and normal subject measurements are presented.     

Effects of increasing arterial pressure on cerebral blood flow in the baboon: Influence of the sympathetic nervous system

The influence of stimulation of the cervical sympathetic chain on the response of cerebral blood flow to hypertension induced by the intravenous infusion of angiotensin was studied in anaesthetised baboons. Cerebral blood flow was measured by the intracarotid¹³³Xenon injection technique. Possible lesions of the blood-brain barrier were studied by injecting Evans blue towards the end of the experiment and ischaemic brain damage was assessed following perfusion fixation.In a control group of five baboons blood flow increased by 53±9% (mean ±S.E.) from the base line values in the arterial pressure range 130–159 mm Hg.In four baboons subjected to unilateral sympathetic stimulation flow increased by 16±4% in the same pressure range.In three babbons subjected to bilateral sympathetic stimulation there were not significant increases in flow until the arterial pressure had increased above 159 mm Hg.Disruption of the blood-brain barrier in the parietooccipital regions was only seen in the control animals but not in the stimulated baboons. Ischaemic brain damage was not observed with the exception of one small lesion in a single stimulated baboon.These findings provide strong support for the observations of Bill and Linder (1976) that activation of the cervical sympathetic can modify the level at which breakthrough of cerebral blood flow occurs in association with systemic hypertension.These investigations were supported by the Medical Research Council and Tenovus (Scotland)