Global cerebral blood flow during infusion of adenosine in humans: assessment by magnetic resonance imaging and positron emission tomography

Adenosine, an endogenous vasodilator, induces a cerebral vasodilation at hypotensive infusion rates in anaesthetized humans. At lower doses (< 100 μg kg^?1 min^?1), adenosine has shown to have an analgesic effect. This study was undertaken to investigate whether a low dose, causing tolerable symptoms of peripheral vasodilation affects the global cerebral blood flow (CBF). In nine healthy volunteers CBF measurements were made using axial magnetic resonance (MR) phase images of the internal carotid and vertebral arteries at the level of C2–3. Quantitative assessment of CBF was also obtained with positron emission tomography (PET) technique, using intravenous bolus []> ¹⁵O]butanol as tracer in four of the subject at another occasion. During normoventilation (5.4 ± 0.2 kPa, mean ± s.e.m.), the cerebral blood flow measured by magnetic resonance imaging technique, as the sum of the flows in both carotid and vertebral arteries, was 863 ± 66 mL min^?1, equivalent to about 64 ± 5 mL 100 g^?1 min^?1. The cerebral blood flow measured by positron emmission tomography technique, was 59 ± 4 mL 100 g^?1 min^?1. All subjects had a normal CO₂ reactivity. When adenosine was infused (84 ± 7 μg kg^?1 min^?1) the cerebral blood flow, measured by magnetic resonance imaging was 60 ± 5 mL 100 g^?1 min^?1. The end tidal CO₂ level was slightly lower (0.2 ± 0.1 kPa) during adenosine infusion than during normoventilation. In the subgroup there was no difference in cerebral blood flow as measured by magnetic resonance imaging or positron emission tomography. In conclusion, adenosine infusion at tolerable doses in healthy volunteers does not affect global cerebral blood flow in unanaesthetized humans.     

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·(100 g)^-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.     

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.     

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.     

Cerebral blood flow and oxygen consumption in the newborn dog

Cerebral blood flow (CBF), CBF responses to changes in arterial CO2 tension, and cerebral metabolic rate for oxygen (CMRO2) were measured in newborn dogs, by means of a modification of the Kety and Schmidt technique employing 133Xe. Mongrel dogs of 1-7 days of age were paralyzed and passively ventilated with 70% N2O and 30% O2. CBF was derived by analysis of paired serial 20-microliter samples of arterial and of cerebral venous blood from the superior sagittal sinus. At an arterial PCO2 of 36.9 +/- 3.7 Torr and a mean arterial blood pressure of 62 +/- 10 Torr, CBF was 23 +/- 8 ml/min per 100 g. The arteriovenous oxygen content difference averaged 5.6 vol%, and CMRO2 was 1.13 +/- 0.30 ml O2/min per 100 g. CBF increased or decreased by 0.58 ml/min/100 g per Torr change in PCO2. Our results suggest that in the newborn, basal CBF and CBF responses to CO2 are considerably lower than in the adult and parallel the lower metabolic needs of the newborn brain.     

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.     

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.     

Quantitative agreement between [15O]H2O PET and model free QUASAR MRI‐derived cerebral blood flow and arterial blood volume

The purpose of this study was to assess whether there was an agreement between quantitative cerebral blood flow (CBF) and arterial cerebral blood volume (CBVA) measurements by [¹⁵O]H₂O positron emission tomography (PET) and model‐free QUASAR MRI. Twelve healthy subjects were scanned within a week in separate MRI and PET imaging sessions, after which quantitative and qualitative agreement between both modalities was assessed for gray matter, white matter and whole brain region of interests (ROI). The correlation between CBF measurements obtained with both modalities was moderate to high (r²: 0.28–0.60, P < 0.05), although QUASAR significantly underestimated CBF by 30% (P < 0.001). CBV_A was moderately correlated (r²: 0.28–0.43, P < 0.05), with QUASAR yielding values that were only 27% of the [¹⁵O]H₂O‐derived values (P < 0.001). Group‐wise voxel statistics identified minor areas with significant contrast differences between [¹⁵O]H₂O PET and QUASAR MRI, indicating similar qualitative CBV_A and CBF information by both modalities. In conclusion, the results of this study demonstrate that QUASAR MRI and [¹⁵O]H₂O PET provide similar CBF and CBV_A information, but with systematic quantitative discrepancies. Copyright © 2016 John Wiley & Sons, Ltd.     

Blood glucose responses in humans mirror lactate responses for individual anaerobic threshold and for lactate minimum in track tests

The equilibrium point between blood lactate production and removal (La^? _min) and the individual anaerobic threshold (IAT) protocols have been used to evaluate exercise. During progressive exercise, blood lactate [La^?]_b, catecholamine and cortisol concentrations, show exponential increases at upper anaerobic threshold intensities. Since these hormones enhance blood glucose concentrations [Glc]_b, this study investigated the [Glc] and [La^?]_b responses during incremental tests and the possibility of considering the individual glucose threshold (IGT) and glucose minimum (Glc_min) in addition to IAT and La^? _min in evaluating exercise. A group of 15 male endurance runners ran in four tests on the track 3000?m run (v _3km); IAT and IGT – 8?×?800?m runs at velocities between 84% and 102% of v _3km; La^? _min and Glc_min– after lactic acidosis induced by a 500-m sprint, the subjects ran 6?×?800?m at intensities between 87% and 97% of v _3km; endurance test (ET) – 30?min at the velocity of IAT. Capillary blood (25?μl) was collected for [La^?]_b and [Glc]_b measurements. The IAT and IGT were determined by [La^?]_b and [Glc]_b kinetics during the second test. The La^? _min and Glc_min were determined considering the lowest [La^?] and [Glc]_b during the third test. No differences were observed (P??1; r?=?0.096; P?? _min [285 (SD 21)] and Glc_min [287 (SD 20) m.?·?min^?1 r?=?0.77; P??]_b reached 5.0? (SD 1.1) and 5.3 (SD 1.0) mmol?·?l^?1 at 20 and 30?min, respectively (P?>?0.05). We concluded that for these subjects it was possible to evaluate the aerobic capacity by IGT and Glc_min as well as by IAT and La^? _min.     

Gaschromatographisches Verfahren für die Blutgasanalysen bei der Hirndurchblutungsmessung nach Kety und Schmidt

Zusammenfassung Es wird über ein gaschromatographisches Verfahren zur Blutgasanalyse bei der Hirndurchblutungsmessung nach Kety u. Schmidt berichtet, das die gleichzeitige quantitative Bestimmung von O₂, N₂, CO₂ und N₂O in einem Trennungsgang gestattet.Mit Hilfe einer geeigneten Schaltung der Gasschleife gelingt es, die durch die Verwendung einer Reaktions- und Äquilibrierkammer bedingte Verbreiterung (tailing) des Kurvenpeaks nach dem Prinzip der abgekürzten Austreibungszeit soweit zu kompensieren, daß bei Verwendung eines umschaltbaren Zweisäulengerätes eine ausreichende Trennung der genannten Peaks erzielt wird.Die Eichung für O₂ und CO₂ erfolgt mit titrierten Lösungen von Perhydrol und Natriumbicarbonat. Die Reproduzierbarkeit der Eichkurven liegt bei 1%. Das Verfahren gestattet eine wesentliche Beschleunigung und automatische Durchfürhrung der Blutgasanalysen bei hoher Meßgenauigkeit.

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Summary To simplify the unconvenient manometric analysis of blood gas content in the determination of cerebral blood flow with the method of Kety and Schmidt, this is a procedure permitting the simultaneous evaluation of oxygen, nitrogen, carbondioxide, and nitrous oxide in a single gaschromatographic run.In contrast to other approaches this arrangement of a special carrier loop allows to compensate the tailing of the peaks derriving from the perfusion of a reaction- and equilibrium vessel. This is the principle of reduced time of discharge, which makes possible the sufficient separation of the peaks using a two column system.Oxygen and carbondioxide calibration is done by means of titrated solutions of perhydrol and sodiumhydrogencarbonate. The reproducibility of the calibration curves lies within 1 per cent.By this method a considerable acceleration and automatisation of the performance of the CBF analysis is obtained adding a high degree of accuracy.

     

Relationship between baseline cerebral blood flow and vascular responses to changes in PaCO2 measured by positron emission tomography in humans: implication of inter-individual variations of cerebral vascular tone

Aim: Inter‐individual variations in normal human cerebral blood flow (CBF) at rest condition have been reported. Inter‐individual variation of cerebral vascular tone is considered to contribute to this, and several determinants of cerebral vascular tone have been proposed. In the present study, the relationship between CBF and cerebral vascular tone to inter‐individual variation at rest condition was investigated using positron emission tomography (PET). Methods: CBF was measured using PET with H₂¹⁵O in each of 20 healthy subjects (20–28 years) under three conditions: at rest (baseline), during hypercapnia and during hypocapnia. The vascular response to change in P_aCO₂ was calculated as the percentage changes in CBF per absolute change in P_aCO₂ in response to hypercapnia and hypocapnia. Results: A significant negative correlation between baseline CBF and the vascular response to hypocapnia was observed in the thalamus, temporal cortex, parietal cortex, occipital cortex and cerebral cortex (P < 0.05). A trend towards negative correlation between baseline CBF and the vascular response to hypocapnia was observed in the cerebellum and putamen (P < 0.1). A significant negative correlation between baseline CBF and the vascular response to hypercapnia was observed in the occipital cortex (P < 0.05). No significant correlation was observed between baseline CBF and haemoglobin concentration, and P_aCO₂. Conclusion: These findings support the assumption that cerebral vascular tone might incline towards vasoconstriction and vasodilatation when baseline CBF is low and high between individuals respectively. Although several determinants of cerebral vascular tone have been proposed, the mechanism of such inter‐individual differences in cerebral vascular tone is unknown.     

Carotid artery stenosis and tachyarrhythmias: regional cerebral blood flow during high-rate ventricular pacing after one vessel occlusion in rats

The aim of the present study was to investigate the effect of hypotensive tachycardias on cerebral blood flow (CBF) in the presence of significant carotid stenosis. The experiments were performed in 57 spontaneously breathing rats during arterial normoxia and normocapnia anesthetized with thiobarbital. CBF was determined with radio-labeled microspheres during control conditions (normofrequent sinus rhythm, normotension; group A; n = 15), during high-rate left ventricular pacing (660–840 ppm) at normotension (group B₁; n = 13), borderline hypotension (group B₂; n = 15) and severe hypotension (group B₃; n = 7). In addition, CBF measurements were performed during borderline hypotension induced by hemorrhage (group C; n = 7). Global CBF was 1.09 ± 0.29 ml g^–1 min^–1 in group A, 0.93 ± 0.40 in group B₁, 0.68 ± 0.31 in group B₂ (P < 0.05 vs. A), 0.42 ± 0.16 in group B₃ (P < 0.05 vs. A) and 0.83 ± 0.2 in group C. The highest CBF values were found in the cerebellum (A; 1.43 ± 0.5 ml g^–1 min^–) and the lowest in the postocclusive tissue of the ipsilateral hemisphere (A; 0.74 ± 0.2 ml g^–1 min^–1). In all groups a 15% mean CBF reduction in the right hemispherical cerebrum in comparison to the left hemisphere was observed (P < 0.01). In contrast, hemispherical CBF of the cerebellum did not differ. The CBF blood pressure relationship shifted to lower CBF values, the threshold of CBF regulation shifted to higher blood pressure values in the tissue regions distal to the occluded vessel during hypotensive tachycardias. One carotid artery occlusion and high rate ventricular pacing seem to be a reliable model for quantifying cerebral hemodynamics during arrhythmias in the presence of carotid stenoses. Using this experimental approach it was demonstrated that hypotensive tachycardias and obstructions within the ectracranial carotid vascular bed such as arterial vessel stenoses and occlusions have an additive effect on CBF reduction.Abbreviations CBF cerebral blood flow - P_m mean arterial blood pressure Correspondence to: A. Hagendorff     

Cerebral oxygenation decreases during exercise in humans with beta‐adrenergic blockade

Aim: Beta‐blockers reduce exercise capacity by attenuated increase in cardiac output, but it remains unknown whether performance also relates to attenuated cerebral oxygenation. Methods: Acting as their own controls, eight healthy subjects performed a continuous incremental cycle test to exhaustion with or without administration of the non‐selective beta‐blocker propranolol. Changes in cerebral blood flow velocity were measured with transcranial Doppler ultrasound and those in cerebral oxygenation were evaluated using near‐infrared spectroscopy and the calculated cerebral mitochondrial oxygen tension derived from arterial to internal jugular venous concentration differences. Results: Arterial lactate and cardiac output increased to 15.3 ± 4.2 mm and 20.8 ± 1.5 L min^?1 respectively (mean ± SD). Frontal lobe oxygenation remained unaffected but the calculated cerebral mitochondrial oxygen tension decreased by 29 ± 7 mmHg (P < 0.05). Propranolol reduced resting heart rate (58 ± 6 vs. 69 ± 8 beats min^?1) and at exercise exhaustion, cardiac output (16.6 ± 3.6 L min^?1) and arterial lactate (9.4 ± 3.7 mm ) were attenuated with a reduction in exercise capacity from 239 ± 42 to 209 ± 31 W (all P < 0.05). Propranolol also attenuated the increase in cerebral blood flow velocity and frontal lobe oxygenation (P < 0.05) whereas the cerebral mitochondrial oxygen tension decreased to a similar degree as during control exercise (delta 28 ± 10 mmHg; P < 0.05). Conclusion: Propranolol attenuated the increase in cardiac output of consequence for cerebral perfusion and oxygenation. We suggest that a decrease in cerebral oxygenation limits exercise capacity.     

Cerebral cortical blood flow in rabbits during parabolic flights (hypergravity and microgravity)

We studied the effect of gravity on cerebral cortical blood flow (CBF), mean arterial blood pressure () and heart rate in six rabbits exposed to parabolic flights. The CBF was obtained using a laser-Doppler probe fixed on to a cranial window. Before weightlessness, the animals were exposed to chest-to-back directed acceleration (1.8–2.0 g). The CBF values were expressed as a percentage of CBF_o (mean CBF during 60 s before the 1st parabola). Propranolol (1 mg · kg⁻¹ IV) was given after the 11th parabola and pentobarbital (12–15 mg · kg⁻¹ IV) after the 16th parabola. Before the administration of the drugs, CBF increased (P < 0.01) during hypergravity [i.e. maximal CBF 151 (SD 64)% CBF_o. Simultaneously increased [maximal , 119 (SD 11) mmHg (P < 0.01)]. At the onset of weightlessness, CBF and reached maximal values [194 (SD 96)% CBF_o (P < 0.01) and 127 (SD 19) mmHg, (P < 0.01) respectively]. The microgravity-induced increase in CBF was transient since CBF returned to its baseline value after 8 (SD 2) s of microgravity. After propranolol administration, CBF was not statistically different during hypergravity but an elevation of CBF was still observed in weightlessness. The increases in CBF and also persisted during weightlessness after pentobarbital administration. These data would indicate that CBF of nonanesthetized rabbits increases during the first seconds of weightlessness and demonstrate the involvement of rapid active regulatory mechanisms since CBF returned to control values within 8 (SD 2) s. We concluded that this elevation in blood flow was not related to stress because it persisted after the administration of propranolol and pentobarbital. Accepted: 6 November 1997     

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 effect of hyperglycaemia on regional cerebral glucose oxidation in humans studied with [1–11C]-D-glucose

The effect of hyperglycaemia on regional cerebral glucose utilization was studied in five healthy males fasted over-night using positron emission tomography. Selectively labelled glucose, [1–¹¹C]-D -glucose, was used as a tracer. After correction for the small loss of [¹¹C]CO₂ from the tissue, this tracer measures the rate of glucose oxidation rather than the total rate of glucose metabolism. Each subject was investigated twice: during normoglycaemia (plasma glucose 5.3 ± 0.3 μmol mL^?1) and at the end of a 2-h period of hyperglycaemia (plasma glucose 13.8 ± 0.7 μmol mL^?1). Assuming unchanged rate constant for loss of labelled CO₂ at normo- and hyperglycaemia the oxidative metabolic rate of glucose was found to be slightly larger at combined hyperglycaemia and hypersulinemia (0.30 ± 0.01 mmol mL^?1 min^?1) than at normal glucose and insulin levels (0.25 ± 0.01 mmol mL^?1 min^?1). This suggests that the process of glucose phosphorylation might not be fully saturated in the human brain or, alternatively, that the glycogen deposition increases during short-term hyperglycaemia. The relative increase of oxidative metabolic rate was considerably larger (≈50%) in white matter than in the brain as a whole (20%). The brain glucose content was found to increase non-linearly with increasing plasma glucose. Together with data from previous studies these results suggest that the free glucose in the human brain is close to zero when the plasma glucose is below 2 μmol mL^?1.     

Breath-to-breath “noise” in the ventilatory and gas exchange responses of children to exercise

The purposes of this investigation were to quantify the noise component of child breath-by-breath data, investigate the major determinants of the breath-to-breath noise, and to characterise the noise statistically. Twenty-four healthy children (12 males and 12 females) of mean (SD) age 13.1 (0.3) years completed 25?min of steady-state cycle ergometry at an exercise intensity of 50?W. Ventilatory and gas exchange variables were computed breath-by-breath. The mean (SD) oxygen consumption (V˙O₂) ranged from 0.72 (0.16) to 0.92 (0.26) l?·?min^?1; mean (SD) carbon dioxide production (V˙CO₂) ranged from 0.67 (0.20) l?·?min^?1 to 0.85 (0.16) l?·?min^?1; and mean (SD) minute ventilation ranged from 17.81 (3.54) l?·?min^?1 to 24.97 (5.63) l?·?min^?1. The majority of the breath-to-breath noise distributions differed significantly from Gaussian distributions with equivalent mean and SD parameters. The values of the normalised autocorrelation functions indicated a negligible breath-to-breath correlation. Tidal volume accounted for the majority of the V˙O₂ (43%) and V˙CO₂ (49%) variance. The breath-to-breath noise can be explained in terms of variations in the breathing pattern, although the large noise magnitude, together with the relatively small attainable response amplitudes in children reduces the certainty with which ventilatory and gas exchange kinetics can be measured.     

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.     

Cerebral blood flow response to acute hypoxic hypoxia

Hypoxic hypoxia (inspiratory hypoxia) stimulates an increase in cerebral blood flow (CBF) maintaining oxygen delivery to the brain. However, this response, particularly at the tissue level, is not well characterised. This study quantifies the CBF response to acute hypoxic hypoxia in healthy subjects. A 20‐min hypoxic (mean P_ETo ₂ = 52 mmHg) challenge was induced and controlled by dynamic end‐tidal forcing whilst CBF was measured using pulsed arterial spin labelling perfusion MRI. The rate constant, temporal delay and magnitude of the CBF response were characterised using an exponential model for whole‐brain and regional grey matter. Grey matter CBF increased from 76.1 mL/100 g/min (95% confidence interval (CI) of fitting: 75.5 mL/100 g/min, 76.7 mL/100 g/min) to 87.8 mL/100 g/min (95% CI: 86.7 mL/100 g/min, 89.6 mL/100 g/min) during hypoxia, and the temporal delay and rate constant for the response to hypoxia were 185 s (95% CI: 132 s, 230 s) and 0.0035 s^–1 (95% CI: 0.0019 s^–1, 0.0046 s^–1), respectively. Recovery from hypoxia was faster with a delay of 20 s (95% CI: –38 s, 38 s) and a rate constant of 0.0069 s^–1 (95% CI: 0.0020 s^–1, 0.0103 s^–1). R₂*, an index of blood oxygenation obtained simultaneously with the CBF measurement, increased from 30.33 s^–1 (CI: 30.31 s^–1, 30.34 s^–1) to 31.48 s^–1 (CI: 31.47 s^–1, 31.49 s^–1) with hypoxia. The delay and rate constant for changes in R₂* were 24 s (95% CI: 21 s, 26 s) and 0.0392 s^–1 (95% CI: 0.0333 s^–1, 0.045 s^–1 ), respectively, for the hypoxic response, and 12 s (95% CI: 10 s, 13 s) and 0.0921 s^–1 (95% CI: 0.0744 s^–1, 0.1098 s^–1/) during the return to normoxia, confirming rapid changes in blood oxygenation with the end‐tidal forcing system. CBF and R₂* reactivity to hypoxia differed between subjects, but only R₂* reactivity to hypoxia differed significantly between brain regions. © 2013 The Authors. NMR in Biomedicine published by John Wiley & Sons, Ltd.