Adaptive changes in cerebral blood flow and oxygen consumption during ethanol intoxication in the rat

Cerebral blood flow (CBF) and oxygen consumption (CMRO₂) were measured during acute and long-term ethanol intoxication in the rat. The purpose was to investigate whether the adaptive changes (development of tolerance) occurring in the CNS during ethanol intoxication were associated with changes in CBF and/or CMRO₂. Consistent with other studies we found that acute severe ethanol intoxication (median blood alcohol concentration (BAC=5.4 mg/ml)) caused a significant decrease in CBF and CMRO₂. After 3–4 days of severe intoxication (BAC of 6.6 mg/ml) these physiological variables were less affected indicating that functional tolerance had developed: CMRO₂ and CBF during acute ethanol intoxication were 9.3 ml/100 g/min and 60 ml/100 g/min respectively; after the long term intoxication period these variables reached 11.2 ml/100 g/min and 78 ml/100 g/min respectively, i.e. values not significantly lower than those of the control group. After induction of hypercapnia (PaCO₂ about 80 mmHg) CBF increased by 360% in the control group; in the acutely intoxicated group CBF increased by only 127% and in the long term intoxicated group by 203 % indicating that the cerebrovascular CO₂-reactivity had also adapted to the ethanol intoxication. It is concluded that adaptive changes of the CNS to chronic ethanol intoxication comprise alterations in CMRO₂, CBF and cerebrovascular reactivity.     

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.     

Effects of indomethacin on cerebral blood flow during hypercapnia in cats

To study the contribution of prostaglandins to cerebral vasodilatation during hypercapnia, we inhibited prostaglandin synthesis with indomethacin. We measured cerebral blood flow (CBF) in anesthetized cats with 15-micrometers microspheres during normocapnia (PCO2 approximately 33 Torr), moderate hypercapnia (PCO2 approximately 49 Torr), and severe hypercapnia (PCO2 approximately 65 Torr) before and after intravenous administration of vehicle or indomethacin (3 and 10 mg/kg). Hypercapnia produced graded increments in blood flow to all areas of the brain. Administration of indomethacin did not change control CBF or significantly attenuate increases in CBF during hypercapnia. We examined efficacy and specificity of inhibition of prostaglandin synthesis by indomethacin using the cranial window method. Arachidonic acid (100 and 200 micrograms/ml) and acetylcholine (10(-7) and 10(-6)M or 10(-6) and 10(-5) M), dissolved in artificial cerebrospinal fluid, dilated pial arteries in a dose-dependent fashion. Intravenous administration of indomethacin blocked vasodilatation produced by arachidonic acid but did not affect the response to acetylcholine. Thus indomethacin, at a dose that effectively blocks prostaglandin synthesis, did not alter resting CBF or attenuate the increase in CBF during hypercapnia. This study suggests that steady-state cerebral vasodilatation during hypercapnia is largely preserved after inhibition of prostaglandin synthesis.     

Redistribution of cardiac output after hypothalamic lesions and hemorrhage

Summary The effects of ablation of the anteroventral portion of the third cerebral ventricle (AV3V) on cardiac output and distribution of regional blood flows were determined in conscious rats using 15 m radiolabelled microspheres before, and 2 min and 15 min after hemorrhage (n=11 for each group). Prior to hemorrhage, cerebral blood flow was significantly greater (216±30 ml/min/100 g), and cerebral vascular resistance was lower (0.60±0.09 mm Hg/ml/min/ 100 g) in rats with AV3V lesions than in controloperated animals (132 ±16 ml/min/100 g; 0.92+0.1 mm Hg/ml/min/100 g, respectively), while mean arterial blood pressure, cardiac output, and regional blood flow to other organs were similar. Less blood was withdrawn from animals with AV3V lesions (4.4 ±0.6 ml) than from control-operated rats (6.0±0.5 ml) to reduce blood pressure to approximately 65 mm Hg. Hemorrhage decreased cerebral vascular resistance in control-operated animals (0.52±0.07 mm Hg/ml/min/100 g), but not in rats with AV3V lesions (0.48±0.1 mm Hg/ml/min/100 g). Cardiac output and regional blood flow to other organs were similar between rats with AV3V lesions and controloperated animals following hemorrhage. These data demonstrate that electrolytic ablation of the AV3V region results in a selective increase in cerebral blood flow and decreased cerebral vascular resistance, but does not alter the reflex changes in regional blood flow evoked by hemorrhage.     

Pancreatic blood flow in hemorrhagic shock

Pancreatic blood flow rates were determined using a¹³³Xe washout technique in a total of 40 dogs, 14 of which were used as a control group and the remaining 26 as the experimental group. The initial pancreatic blood flow rates of control group and of the experimental group were 85.1±10.1 ml/100g/min of pancreas/min and 81.1±5.4 ml/100g/min respectively. These values were not significantly different from each other (P>0.05). In the control group the blood flow was determined 3 times at 30 min intervals. These mean values were 73.0±9.4, 74.6±8.7, and 79.4 ±10.4 ml/100g/min respectively (P>0.05). The dogs in the experimental group were bled and the peripheral arterial blood pressure was reduced stepwise to 80, 50, and 30 mm Hg. At each level a 30 min of stabilization period the pancreatic blood flow rates were 49.8±3.7, 29.3±2.3 and 20.2±2.3 ml/100g/min respectively. These mean values were very significantly reduced compared to those of the control group, at 30 min (P<0.02), at 60 and 90 min (P>0.001). They were also very significantly different from their own initial values (P<0.001). the metabolic consequences of this reduction in pancreatic blood flow are discussed.This study was supported in part by grants No. 264 and 315 of Turkish Scientific and Technical Research Council     

Local blood flow in the thalamus and frontal cortex in alert and narcotized dogs

The magnitude of the local blood flow in the thalamus and cerebral cortex is studied on 22 sexually mature nonpedigree dogs. Mean values of local blood flow are obtained in alert animals, and the effect of narcosis (nitrous oxide) on the local cerebral blood flow is studied. The mean local blood flow in alert dogs is found to be 84.8±2.9 ml/100 g/min in the cerebral cortex and 68.7±1.6 ml/100 g/min in the thalamus. Insignificant fluctuations are found during a dynamic recording of the local blood flow during 7 days. Under narcosis (70% nitrous oxide) the local blood flow decreases 3–12%. According to the findings, nitrous oxide narcosis does not significantly affect the brain circulation, so that it is suitable for an experimental study of the latter.Translated from Fiziologicheskii Zhurnal SSSR imeni I. M. Sechenova, Vol. 73, No. 10, pp. 1321–1324, October, 1987.     

Regional cerebral blood flow during acute hypoxia in individuals susceptible to acute mountain sickness

Individuals susceptible to high altitude pulmonary edema show altered pulmonary vascular responses within minutes of exposure to hypoxia. We hypothesized that a similar acute-phase vulnerability to hypoxia may exist in the brain of individuals susceptible to acute mountain sickness (AMS). In established AMS and high altitude cerebral edema, there is a propensity for vasogenic white matter edema. We therefore hypothesized that increased cerebral blood flow (CBF) during acute hypoxia would also be disproportionately greater in white matter (WM) than grey matter (GM) in AMS-susceptible subjects. We quantified regional CBF using arterial spin labeling MRI during 30 min hypoxia (F(I)O(2) = 0.125) in two groups: AMS-susceptible (AMS-S, n = 6) who invariably experienced AMS at altitude, and AMS-resistant (AMS-R, n = 6) who never experienced AMS despite multiple rapid ascents to high altitude. SaO(2) during hypoxia did not differ between groups (AMS-S = 87+/-4%, AMS-R = 89+/-3%, p = 0.3). Steady-state whole-brain CBF increased in hypoxia (p<0.005), but did not differ between groups (normoxia: AMS-S = 42.7+/-14.0 ml/(100 g min), AMS-R = 41.7+/-10.1 ml/(100 g min); hypoxia: AMS-S = 47.8+/-19.5 ml/(100 g min), AMS-R = 48.2+/-10.1 ml/(100 g min), p = 0.65), and cerebral oxygen delivery remained constant. The percent change in CBF did not differ between brain regions or between groups (although absolute CBF change was greater in GM): (GM: AMS-S = 6.1+/-7.7 ml/(100 g min) (10+/-11%), AMS-R = 8.3+/-5.7 ml/(100 g min) (17+/-11%), p = 0.57; WM: AMS-S = 4.3+/-5.1 ml/(100 g min) (12+/-15%), AMS-R = 4.8+/-2.9 ml/(100 g min) (16+/-9%), p = 0.82). CONCLUSION: CBF increases in acute hypoxia, but is not different between WM and GM, irrespective of AMS susceptibility. Acute phase differences in regional CBF during acute hypoxia are not a primary feature of susceptibility to AMS.     

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.     

The effect of stepwise arterial hypotension on blood flow and oxidative metabolism of the brain

Summary With the Kety-Schmidt-technique in ten dogs anaesthetized with 0.5% halothane, blood flow and oxidative metabolism of the brain were studied during stepwise lowering of CPP due to arterial hypotension at 71 and 41 torr. CBF remained constant (65.6 and 64.1 ml/100 g min) when CPP dropped from 98 to 71 torr, but at a CPP of 41 torr CBF fell to 32.2 ml/100 g min, i. e. to about 50% of the resting value. The CMR-oxygen did not change (4.20 and 4.38 ml/100 g min) when CPP was reduced from about 100 to about 70 torr, but decreased to 2.90 ml/100 g min, i. e. about 70% of the resting value in deep arterial hypotension.The uptake of glucose changed from 4.62 to 6.19 mg/100 g min as well as the output of CO₂ and lactate (from 4.64 to 6.57 ml/100 g min and from 0.33 to 1.62 mg/100 g min) when CPP was decreased to 71 torr. It could be demonstrated that at this CPP range the oxidative metabolism was unchanged. It was assumed that the increased uptake of glucose was only to form lactate, and that this non-hypoxic lactate production was responsible for the elevated CO₂ release. At a CPP range of 41 torr the metabolic rates of glucose and CO₂ decreased to 3.33 mg/100 g min and to 3.37 ml/100 g min, respectively, while the output of lactate remained relatively high (1.14 mg/100 g min). These findings support the assumption that at a CPP range of 41 torr the oxidative metabolism of the brain becomes insufficient. All findings demonstrate close interactions between cerebral flow blood and oxidative brain metabolism in arterial hypotension. In deep arterial hypotension respiratory acidosis has an effect on CBF. The increase of CBF is accompanied by an improvement of CMR-oxygen but not of CMR-glucose. Although CMR-lactate is reduced, the lactate/glucose index remains high.     

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.     

Adaptive changes in cerebral blood flow and oxygen consumption during ethanol intoxication in the rat..

Cerebral blood flow (CBF) and oxygen consumption (CMRO2) were measured during acute and long-term ethanol intoxication in the rat. The purpose was to investigate whether the adaptive changes (development of tolerance) occurring in the CNS during ethanol intoxication were associated with changes in CBF and/or CMRO2. Consistent with other studies we found that acute severe ethanol intoxication (median blood alcohol concentration (BAC = 5.4 mg/ml)) caused a significant decrease in CBF and CMRO2. After 3-4 days of severe intoxication (BAC of 6.6 mg/ml) these physiological variables were less affected indicating that functional tolerance had developed: CMRO2 and CBF during acute ethanol intoxication were 9.3 ml/100 g/min and 60 ml/100 g/min respectively; after the long term intoxication period these variables reached 11.2 ml/100 g/min and 78 ml/100 g/min respectively, i.e. values not significantly lower than those of the control group. After induction of hypercapnia (PaCO2 about 80 mmHg) CBF increased by 360% in the control group; in the acutely intoxicated group CBF increased by only 127% and in the long term intoxicated group by 203% indicating that the cerebrovascular CO2-reactivity had also adapted to the ethanol intoxication. It is concluded that adaptive changes of the CNS to chronic ethanol intoxication comprise alterations in CMRO2, CBF and cerebrovascular reactivity.     

Cerebral circulatory responses to hypercapnia and hypoxia in the recovery period following complete and incomplete cerebral ischemia in the rat

In this study we examined the reactions of cerebral vessels to hypercapnia and hypoxia during the recovery period following cerebral ischemia. We used ventilated, lightly anesthetized rats and induced complete ischemia by CSF compression, incomplete ischemia by bilateral carotid occlusion combined with hypotension. After 15 min of ischemia and 60 min of recirculation the animals were rendered hypercapnic or hypoxic for 2–3 min and local CBF was then measured autoradiographically with ¹⁴C-iodoantipyrine. Following complete ischemia vascular CO₂ responsiveness was abolished or attenuated in most structures analysed. However, there was a considerable interstructural heterogeneity. For example, in the cerebellum and the red nucleus flow rates were observed which approached values obtained in hypercapnic control animals, whereas CO₂ responsiveness was abolished in several cortical areas and hippocampus. The response to CO₂ following incomplete (“forebrain”) ischemia varied considerably. In the cerebral cortices areas with low flow rates were often mixed with hyperemic zones, and in most structures that had very low flow rates during ischemia, CO₂ responsiveness was lost or grossly attenuated. Structures that had suffered moderate or only mild ischemia had better retained or completely preserved CO₂ response. The cerebrovascular reaction to hypoxia was found to be attenuated in most, but not abolished in any of the structures examined. In general, the vascular response to hypoxia was better preserved than that to hypercapnia. Reactivity was similar following complete and incomplete ischemia. As observed during hypercapnia, there were pronounced interstructural variations with considerable increases in flow rates e.g. in the substantia nigra and the cerebellum.     

Sympathetic Withdrawal Augments Cerebral Blood Flow During Acute Hypercapnia in Sleeping Lambs

Study Objectives:

Cerebral sympathetic activity constricts cerebral vessels and limits increases in cerebral blood flow (CBF), particularly in conditions such as hypercapnia which powerfully dilate cerebral vessels. As hypercapnia is common in sleep, especially in sleep disordered breathing, we tested the hypothesis that sympathetic innervation to the cerebral circulation attenuates the CBF increase that accompanies increases in PaCO₂ in sleep, particularly in REM sleep when CBF is high.

Design:

Newborn lambs (n = 5) were instrumented to record CBF, arterial pressure (AP) intracranial pressure (ICP), and sleep-wake state (quiet wakefulness (QW), NREM, and REM sleep). Cerebral vascular resistance was calculated as CVR = [AP-ICP]/CBF. Lambs were subjected to 60-sec tests of hypercapnia (FiCO₂ = 0.08) during spontaneous sleep-wake states before (intact) and after sympathectomy (bilateral superior cervical ganglionectomy).

Results:

During hypercapnia in intact animals, CBF increased and CVR decreased in all sleep-wake states, with the greatest changes occurring in REM (CBF 39.3% ± 6.1%, CVR −26.9% ± 3.6%, P < 0.05). After sympathectomy, CBF increases (26.5% ± 3.6%) and CVR decreases (−21.8% ± 2.1%) during REM were less (P < 0.05). However the maximal CBF (27.8 ± 4.2 mL/min) and minimum CVR (1.8 ± 0.3 mm Hg/ min/mL) reached during hypercapnia were similar to intact values.

Conclusion:

Hypercapnia increases CBF in sleep and wakefulness, with the increase being greatest in REM. Sympathectomy increases baseline CBF, but decreases the response to hypercapnia. These findings suggest that cerebral sympathetic nerve activity is normally withdrawn during hypercapnia in REM sleep, augmenting the CBF response.

Citation:

Cassaglia PA; Griffiths RI; Walker AM. Sympathetic withdrawal augments cerebral blood flow during acute hypercapnia in sleeping lambs. SLEEP 2008;31(12):1729–1734.     

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     

Role of tissue hypoxia in cerebrovascular regulation: a mathematical modeling study

This paper presents a mathematical model of cerebrovascular regulation, in which emphasis is given to the role of tissue hypoxia on cerebral blood flow (CBF). In the model, three different mechanisms are assumed to work on smooth muscle tension at the level of large and small pial arteries: CO₂reactivity, tissue hypoxia, and a third mechanism necessary to provide good reproduction of autoregulation to cerebral perfusion pressure (CPP) changes. Using a single set of parameters for the mechanism gains, assigned via a best fitting procedure, the model is able to reproduce the pattern of pial artery caliber and CBF under a large variety of physiological stimuli, either acting separately (hypoxia, CPP changes, CO₂ pressure changes) or in combination (hypercapnia+hypoxia; hypercapnia+hypotension). Furthermore, the model can explain the increase in CBF and the vasoconstriction of small pial arteries observed experimentally during hemodilution, ascribing it to the decrease in blood viscosity and to the antagonistic action of the flow-dependent mechanism (responsible for vasoconstriction) and of hypoxia (responsible for vasodilation). Finally, the interaction between hypoxia and intracranial pressure (ICP) has been analyzed. This interaction turns out quite complex, leading to different ICP time patterns depending on the status of the cerebrospinal fluid outflow pathways and of intracranial compliance. © 2001 Biomedical Engineering Society. PAC01: 8719Uv, 8719Tt, 8719Ff, 8380Lz     

Longitudinal MRI studies in the isoflurane-anesthetized rat: long-term effects of a short hypoxic episode on regulation of cerebral blood flow as assessed by pulsed arterial spin labelling

MRI is a powerful tool for measuring cerebral blood flow (CBF) longitudinally. However, most animal studies require anesthesia, potentially interfering with normal physiology. Isoflurane anesthesia was used here to study CBF regulation during repetitive scanning in rats. MR perfusion images were acquired using FAIR (flow-sensitive alternating inversion recovery) arterial spin labeling, and absolute CBF was calculated. CBF changes in response to a hypoxic (12% O2) and hypercapnic (5% CO2) gas stimulus were monitored. Hypercapnia led to a robust increase in CBF compared with baseline (195.5+/-21.5 vs 123.6+/-17.9 ml/100 g/min), and hypoxia caused a smaller non-significant increase in mean CBF values (145.4+/-13.4 ml/100 g/min). Strikingly, when measurements were repeated 5 days later, CBF was dramatically reduced in hypoxia (93.2+/-8.1 ml/100 g/min) compared with the first imaging session. Without application of the hypoxic and hypercapnic gases during the first MRI, baseline CBF and CBF changes in response to hypoxia at the second MRI were similar to naive rats. Blood gas analyses revealed a slight reduction in arterial oxygenation during the second period of anesthesia compared with the first. These findings indicate that, in isoflurane-anesthetized rats, even a short hypoxic episode can have long-lasting effects on cerebrovascular regulation.     

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.     

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.     

Caudal ventrolateral medullary depressor area controls cerebral circulation via rostral ventrolateral medullary pressor area

The cerebral blood flow (CBF) was determined by radiolabeled microsphere technique in urethane (1.1–1.5 g·kg^–1, i.p.) anesthetized Wistar rats. Microinjection of L-glutamate (1.7 nmol) into the ventrolateral medullary depressor area (VLDA) produced a significant (P<0.01) decrease in CBF from 64±9 (mean ± S.E.M.) to 48±9 ml·min^–1·(100g)^–1 and a significant (P<0.01) increase in cerebrovascular resistance (CVR) from 1.7±0.2 to 2.4±0.4 mmHg per [ml·min^–1(100g)^–1] in the cerebral cortex ipsilateral to the stimulated VLDA side but not in other structures such as brain stem and cerebellum (n=9). Cervical sympathectomy blocked the decrease in CBF and increase in CVR elicited by chemical stimulation of the VLDA (n=10). Depression of the ventrolateral medullary pressor area (VLPA) neurons induced by microinjection of muscimol into the VLPA blocked the CBF decrease and CVR increase following chemical stimulation of the VLDA (n=11). Microinjection of the vehicle solution into the VLDA had no effects on systemic and cerebral circulation (n=7). These results suggest that a vasoconstrictor pathway to control cerebral vessels involves an excitatory projection from the VLDA to the VLPA and the changes in cerebral circulation are mediated by the cervical sympathetic nerves.