Significant Decrease In Cerebral Blood Flow Research Articles

O-15]H2O Positron Emission Tomography Determination of Cerebral Blood Flow Reserve after Intravenous Acetazolamide during Balloon Test Occlusion of the Internal Carotid Artery

The purpose of this paper was to evaluate the effects of acetazolamide on cerebral blood flow (CBF) measured by [O-15]H2O positron emission tomography (PET) during balloon test occlusion (BTO) of the internal carotid artery (ICA). [O-15]H2O PET cerebral blood flow studies were completed in 20 patients undergoing BTO CBF determinations were obtained without carotid occlusion as a baseline, following balloon occlusion, and as a third scan with balloon occlusion after an intravenous acetazolamide bolus. The balloon was left deflated between scans, and was only inflated immediately before and during the 90 second period of time needed for CBF determination. Significance was determined at the P < 0.05 level. Two of twenty studies were technical failures. Prior to acetazolamide there was a significant decrease in CBF (P < 0.0007) ipsilateral to the occlusion. After acetazolamide administration there was no statistically significant change in flow on the occluded side (P < 0.3047); however, there was a significant increase in cerebral blood flow (P < 0.0002) on the non-occluded side. In this patient population, there was no acetazolamide-induced CBF decompensation (steal) phenomenon or haemodynamically significant risk in CBF ipsilateral to the occlusion.

Society of Neurosurgical Anesthesia and Critical Care

Society of Neurosurgical Anesthesia and Critical Care

Reduced cerebral blood flow, oxygen delivery, and electroencephalographic activity after traumatic brain injury and mild hemorrhage in cats.

The authors investigated the effects of transient, mild hemorrhagic hypotension after fluid-percussion traumatic brain injury on intracranial pressure, cerebral blood flow (CBF), cerebral oxygen delivery (CBF x arterial O2 content), and electroencephalographic (EEG) activity. Adult mongrel cats were anesthetized with 1.6% isoflurane in N2O:O2 (70:30) and prepared for trauma and for radioactive microsphere CBF measurement. Isoflurane concentration was decreased to 0.8%, and the cats were randomly assigned to one of four control groups or to an experimental group. Animals in the four control groups underwent either mild hemorrhage (18 ml.kg-1) immediately followed by resuscitation with equal volumes of 10% Hetastarch (eight cats), mild hemorrhage followed by replacement of shed blood (six cats), isovolemic hemodilution with 18 ml.kg-1 of Hetastarch (six cats), or moderate (2.2 atm) trauma alone (eight cats). The experimental group received a combination of trauma and mild hemorrhage followed by resuscitation with Hetastarch (eight cats). Mild hemorrhage produced no significant changes in CBF, renal blood flow, or cardiac output. Following resuscitation from mild hemorrhage, mean arterial blood pressure, cardiac output, renal blood flow, and CBF were not significantly different from baseline; cardiac output and renal blood flow did not differ significantly from baseline 2 hours after Hetastarch resuscitation. Neither hemorrhage nor trauma alone produced significant decreases in CBF or in EEG activity, but trauma followed by hemorrhage and resuscitation produced significant (p less than 0.01) decreases in CBF, cerebral oxygen delivery, and EEG score. These data demonstrate that, following traumatic brain injury, even mild hemorrhagic hypotension is associated with significant deficits in cerebral oxygen availability and neurological function.

Intravenous fluid tonicity: effect on intracranial pressure, cerebral blood flow, and cerebral oxygen delivery in focal brain injury

An investigation into the role of intravenous fluid tonicity in determining intracranial pressure (ICP) after brain injury is described. The authors compare the results of infusion of a hypotonic fluid (Ringer's lactate, 270 mOsm/liter) to those of a hypertonic fluid (hypertonic sodium lactate, 500 mOsm/liter) in a porcine model of focal cryogenic brain injury. Hemodynamic parameters (ICP, regional cerebral blood flow (CBF), and oxygen delivery) and serum osmolarity were measured every 3 hours for 24 hours after injury. At sacrifice, the water content of the lesioned and nonlesioned cortex was determined by specific gravity. The cryogenic injury produced a significant increase in ICP and a significant decrease in CBF in all experimental groups. Maintenance infusion of hypertonic sodium lactate for 24 hours resulted in significantly lower ICP, higher CBF and oxygen delivery, and higher serum osmolarity than Ringer's lactate infusion. Cortical water content in the area of the lesion was similar in both groups, but in the uninjured hemisphere it was significantly lower in the hypertonic group. These data suggest that hypertonic maintenance fluid improves intracranial compliance by dehydrating uninjured cortex. Improved CBF in the hypertonic group may be due to dehydration of cerebrovascular endothelium and erythrocytes. By reducing ICP and improving CBF, hypertonic fluid administration may thus reduce secondary brain injury after head trauma.

Simultaneous transcranial Doppler sonography and cerebral blood flow measurements of cerebrovascular CO2-reactivity in patients with aneurysmal subarachnoid haemorrhage

Transcranial Doppler sonography (TCD) flow velocities and cerebral blood flow (CBF) measurements were evaluated in 14 patients who had suffered a major aneurysmal subarachnoid hemorrhage (SAH). Cerebrovascular reactivity to hypocapnia was evaluated simultaneously by the two methods. The measurements were performed under general anaesthesia preoperatively, within 72 hours after the bleed, during normocapnia and hypocapnia. There was poor correlation between absolute values of hemispheric CBF and corresponding TCD mean flow velocity. Controlled hyperventilation was associated with a significant decrease in CBF as well as TCD flow velocity (p less than 0.001). In terms of reactivity indices the correlation between the two methods was poor and not significant (r = 0.33, p = 0.09). The principal differences between the methods are discussed as well as the application of TCD in the evaluation of cerebrovascular reactivity.

Behavioral and cerebrovascular effects of caffeine in patients with anxiety disorders

Caffeine is believed to induce anxiety in normal people and anxiety disorder patients and panic attacks in panic disorder patients. The drug is also known to reduce cerebral blood flow (CBF). Findings suggesting an anxiety-related cerebral vasoconstrictive factor have been reported. We examined the relationship between changes in anxiety and CBF induced by intravenously injecting 250 mg of caffeine (comparable to 2 cups of coffee) in 8 patients with generalized anxiety disorder, 9 patients with panic disorder and 9 normal controls. CBF measurements were also obtained before and after an injection of normal saline in another group of 9 normal volunteers. The anxiety disorder patients did not show any evidence of increase in anxiety and panic after caffeine. Both patients and controls who received caffeine but not normal controls who received saline showed significant CBF decrease. The CBF changes were unrelated to changes in mood, autonomic activity and carbon dioxide levels.

Intracranial and Spinal Cord Hemodynamics in the Sitting Position in Dogs in the Presence and Absence of Increased Intracranial Pressure

The effect of the sitting position on cerebral blood flow (CBF), spinal cord blood flow (SCBF), and cerebral metabolic rate for oxygen (CMRo2) was studied in anesthetized dogs with and without increased intracranial pressure. Blood flow measurements were made at four time periods: (a) initial supine; (b) after 5 min in the sitting position; (c) after 60 min in the sitting position; and (d) 15 min after resuming the supine position. Six dogs (group 1) served as a control group with a normal intracranial pressure (ICP). In five dogs (group 2) ICP was elevated with a parietal epidural balloon 1 h before the first measurements of blood flows were made. Saline was injected incrementally into the balloon so as to reach a steady-state ICP of 30 mm Hg for 1 h. Elevation of ICP in group 2 resulted in significantly lower CBF, SCBF, and CMRo2 compared with group 1. Postural changes in group 1 did not result in any significant change in blood flow measurements whereas in group 2, after 1 h in the sitting position, there were significant decreases in CBF and SCBF compared with the initial supine measurements. There was, however, no corresponding decrease in CMRo2 in group 2 with change in position. These data suggest that both the brain and spinal cord may be at risk for ischemia during sitting position procedures under general anesthesia in the presence of elevated ICP.

Effect of Indomethacin on the Regulation of Cerebral Blood Flow during Respiratory Alkalosis in Newborn Piglets

The effect of cyclooxygenase inhibition by indomethacin on regional cerebral blood flow (CBF) during hypocapnia induced by hyperventilation and during hypercapnia induced by CO2 inhalation was examined. CBF was measured in 27 anesthetized, ventilated piglets (2-8 d) using microspheres in control and indomethacin treated animals (5 mg/kg) after hyperventilation or inhalation of 6% CO2. In the control group (n = 6), CBF decreased significantly (p less than 0.05) to all regions of the brain after hyperventilation with a 32% decrease in the cerebral cortex. In the indomethacin-treated group (n = 6), blood flow significantly decreased by 35 to 49% in all regions of the brain, except the cerebral white matter, during normocapnia with no further decrease in flow during subsequent hypocapnia. Although CBF increased significantly after indomethacin treatment during hypercapnia the response was markedly attenuated with blood flow to the cerebral gray matter, hippocampus and pons rising only 42, 25, and 42% in contrast to 108, 75, and 225% in the control group. Since indomethacin decreased resting CBF, unilateral sympathetic nerve stimulation at 15 Hz was used to test the specificity of indomethacin on hypocapnic vasoconstriction (n = 5). Unilateral sympathetic nerve stimulation caused a further statistically significant decrease in CBF on the stimulated side after hyperventilation with indomethacin (12%), which was comparable to that which occurred during normocapnia (16%). The data demonstrate that indomethacin attenuates the cerebrovascular sensitivity to both increases and decreases in CO2/H+ and implicate a possible role for vasoactive prostanoids in mediating the response of CBF to fluctuations in CO2 in newborn piglets.

Cerebral blood flow and interstitial fluid adenosine during hemorrhagic hypotension

This study was designed to assess the role of adenosine in autoregulation of cerebral blood flow (CBF) with the use of the brain dialysis technique to sample cerebral interstitial fluid (ISF) and hydrogen clearance to measure local CBF in ketamine-anesthetized rats. In group 1 (n = 11), animals were hemorrhaged to reduce mean arterial blood pressure (MABP) from control levels (MABP = 101.1 +/- 2.6) to 80, 70, 60, 50, 40, and 30 mmHg. Cerebral autoregulation was evidenced by no significant decrease in CBF until MABP decreased to 60 mmHg. However, dialysate adenosine concentration did not increase until MABP decreased to 50 mmHg. In group 2 (bilateral dialysis; n = 11), in which the left carotid artery was ligated before reductions in MABP, left-side dialysate adenosine concentration increased at a MABP of 70 mmHg. In group 3 (bilateral dialysis; n = 6), one dialysis probe was perfused with artificial cerebrospinal fluid containing 10(-3) M 8(p-sulfophenyl)theophylline (8-SPT), an adenosine receptor antagonist, during reduction of MABP to 50 mmHg. Although there were similar reductions in CBF with or without adenosine receptor blockade, dialysate adenosine concentration was greater on the side of locally infused 8-SPT at a MABP of 50 mmHg. These data suggest that adenosine is not responsible for cerebral autoregulation at blood pressures greater than 50 mmHg but may contribute to the decrease in cerebral vascular resistance observed at arterial pressures below the autoregulatory range.

Theophylline Effect on the Cerebral Blood Flow Response to Hypoxemia

Cerebral oxygen delivery (CO2D) remains nearly constant over a wide range of cerebral perfusion pressure and arterial oxygen content. In response to a decrease in arterial oxygen content secondary to hypoxemia, cerebral blood flow (CBF) increases, a response likely mediated by the release of adenosine. We studied the effect of theophylline, a potent adenosine antagonist, on CBF and cerebral oxygen delivery (CO2D) during hypoxemia in five healthy adult male volunteers. The CBF was measured using 133Xe clearance under conditions of (1) normoxemia (O2 saturation greater than 95 percent); (2) hypoxemia (O2 saturation = 80 percent); (3) normoxemia following aminophylline (the ethylene diamine salt of theophylline) 6 mg/kg intravenously; and (4) hypoxemia following aminophylline. Aminophylline decreased CBF and CO2D during both normoxemia and hypoxemia, but did not prevent the increase in CBF accompanying hypoxemia, suggesting that the increase in CBF in response to hypoxemia may not be mediated by adenosine or that customary doses of aminophylline are insufficient to inhibit adenosine-mediated cerebral vasodilation in response to hypoxemia. The significant decrease in CBF and CO2D observed following aminophylline is potentially clinically important and should be considered in the selection of bronchodilator therapy.

Beagle pup model of perinatal asphyxia: nimodipine studies.

Calcium antagonists may be of significant benefit in the pharmacotherapy of cerebral ischemia, possibly by improving postischemic cerebral blood flow (CBF). This study evaluated the effects of the calcium antagonist nimodipine on CBF in a newborn beagle pup model of perinatal asphyxia lasting 5 minutes. Immediately after the asphyxial episode, nimodipine (2 micrograms/kg/min) or saline was infused for 10 minutes, following which [14C]iodoantipyrine determinations of CBF were performed. In noninsulted pups, nimodipine caused both significant decreases in CBF to cortical and deep gray structures as well as a decrease in mean arterial blood pressure (MABP) (p less than 0.05). In insulted pups, nimodipine similarly decreased MABP (p less than 0.001) and CBF to cortical and deep gray matter regions. Nimodipine appeared to have no effect on arterial blood gases and EEG tracings in either insulted or noninsulted pups. Although nimodipine may be shown to improve neurologic outcome in asphyxiated newborn infants, the limits of this study do not show the mechanism to be that of improving CBF.

Effect of lidoflazine on cerebral blood flow and neurologic outcome when administered after complete cerebral ischemia in dogs.

This study tested the hypothesis that lidoflazine, a calcium entry blocking drug, will improve post-ischemic neurologic outcome when administered after a period of complete cerebral ischemia, and that the improvement in outcome is related to an increase in post-ischemic cerebral blood flow (CBF). Complete cerebral ischemia was produced in 31 dogs by temporary ligation of the aorta and venae cavae. In six dogs, 10 min of complete cerebral ischemia was followed by an infusion of lidoflazine 1.0 mg X kg-1 iv over 10 min. CBF and cerebral metabolic rate for oxygen (CMRO2) were measured pre-ischemia, and for 90 min post-ischemia. The results from these six dogs were compared with results previously obtained from eight untreated dogs under similar, but not identical, conditions. The CBF measured post-ischemia in the dogs administered lidoflazine did not differ from the CBF measured post-ischemia in the untreated dogs. Both groups showed an initial hyperemia post-ischemia, followed by significant decreases in CBF from control values by 35 min post-ischemia. The post-ischemic CMRO2 also did not differ between lidoflazine treated and untreated groups. In 25 dogs, 11 min of complete cerebral ischemia was followed by an iv infusion of either lidoflazine 1.0 mg X kg-1 or saline placebo. The same iv infusions were repeated at 8 and 16 h post-ischemia. Seven dogs were excluded from data analysis for failure to meet pre-established protocol criteria. Neurologic injury was evaluated in the remaining dogs at 48 h post-ischemia by an observer blinded to the treatment groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Reversibility of hemodynamic hypofrontality in schizophrenia.

Regional cerebral blood flow (CBF) was studied in 51 young schizophrenics. A significant decrease of CBF was seen in frontal and prefrontal regions (hypofrontal pattern) in chronic patients whose disease had evolved for more than 2 years and who were in remission. This hypofrontal pattern was reversible, as it disappeared during exacerbation of the disease. In 10 patients who had not been treated with neuroleptics for several weeks, we found a dopaminergic hypersensitivity in the frontal lobes, as a weak dose of piribedil restored near-normal frontality. This may reflect either the role of neuroleptic washout or a primitive dopaminergic depletion, as proposed by some authors in the chronic form of schizophrenia.

Influence of sufentanil on cerebral metabolism and circulation in the rat.

The authors examined the effects of large intravenous doses of sufentanil (5-160 micrograms/kg) on cerebral blood flow (CBF) and cerebral metabolic rate for oxygen (CMRO2) in rats. CBF and CMRO2 were measured by a modified Kety-Schmidt technique using 133Xenon washout. Progressive decreases in CBF and CMRO2 occurred in animals receiving sufentanil. The maximum decrease was 53% and 40% for CBF and CMRO2 respectively, at a dose of 80 micrograms/kg. The values for CBF and CMRO2 in this group were 105 +/- 10 ml X 100 g-1 X min-1 (mean +/- SEM) and 6.5 +/- 0.5 ml X 100 g-1 X min-1, respectively, compared with 226 +/- 28 ml X 100 g-1 X min-1 and 10.9 +/- 1 ml X 100 g-1 X min-1 in the control group, which received N2O 70% in oxygen. Larger doses of sufentanil did not cause further significant changes in CBF and CMRO2. Sharp waves appeared on the electroencephalogram (EEG) of all the animals following sufentanil injection, and some animals had EEG changes develop consistent with seizure activity. This seizure-like activity appeared to consist of a single episode of short duration in the groups receiving 5, 10, and 20 micrograms/kg sufentanil. The incidence and frequency of seizure activity increased in the groups receiving higher doses of sufentanil, although the duration of seizures was still short. The results of this study indicate that sufentanil causes a significant decrease in CBF and CMRO2 similar to that previously reported for fentanyl, and high doses of sufentanil may cause frequent seizure-like patterns appearing on EEG.

Cerebral blood flow and ICP patterns in patients with communicating hydrocephalus after aneurysm rupture.

Cerebral blood flow (CBF) was measured, the intracranial pressure (ICP) was continuously recorded, and the ventricular system size was evaluated on serial computerized tomography scans in 43 patients. These patients all had communicating hydrocephalus after subarachnoid hemorrhage (SAH) from rupture of an intracranial aneurysm. The studies were carried out both in the acute stage (within 7 days after SAH) and in the communicating hydrocephalus stage. In patients in the acute stage who had no ventricular dilatation, but who later developed communicating hydrocephalus, the mean CBF was reduced; lower CBF was associated with poorer clinical grades and a higher resting pressure range. Communicating hydrocephalus produced a significant decrease in CBF. The ICP tracing showed continuing plateau waves in conjunction with B-waves in patients in whom recordings were begun within 63 days after SAH. In general, patients with more dilated ventricular systems, with less frequent ICP irregularities, and with lower resting pressure ranges had a more marked decrease in CBF. A significant decrease in CBF was also found in patients with diffuse vasospasm in comparison to those without vasospasm. Patients with communicating hydrocephalus in whom ICP recordings were started more than 6 months after SAH showed no ICP irregularities. In these patients, a mean CBF of less than 25 ml/100 gm/min and a markedly low resting pressure range were observed. Shunting procedures were never effective in any of these patients. The results suggest that, in patients with communicating hydrocephalus, a mean CBF below this level may cause irreversible damage to the brain tissue in the terminal stage, and may inhibit the cerebral vasomotor reaction that participates in the development of ICP irregularities.

The influence of antihypertensive therapy on cerebral autoregulation in aged hypertensive rats.

Cerebrovascular responses to hemorrhage induced hypotension were tested in aged (24 month) spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto (WKY) after ten weeks of antihypertensive drug or sham treatment. Antihypertensive drug treatment consisted of 1 mg/kg/day minoxidil, 4 mg/kg/day hydralazine and 4 mg/kg/day propranolol given in the drinking water. Antihypertensive therapy produced a 30% decrease in systolic blood pressure in aged SHR to levels not significantly different from sham treated WKY. Cerebral blood flow (CBF), measured under control conditions using ketamine anesthesia, was not significantly different between sham and drug treated SHR and WKY. Cerebral oxygen metabolic rate (CMRO2) was significantly decreased in drug treated SHR and WKY compared to sham treated rats. Lowering blood pressure to a level between 80 and 95 torr produced no significant change in CBF or CMRO2 in sham or drug treated WKY or antihypertensive treated SHR, but a produced a significant decrease it both CBF and CMRO2 in sham treated SHR. Decreasing mean blood pressure to 50-60 torr produced a significant decrease in CBF but not CMRO2 in both WKY treatment groups and in hypertensive treated SHR, but again in sham treated SHR both CBF ana CMRO2 were significantly decreased. These results indicate that aged hypertensive rats are unable to maintain CBF or CMRO2 under even moderate hypotensive test conditions, and that cerebral autoregulation can be improved with antihypertensive therapy.

Effects of prostaglandins on the cerebral circulation in the goat

The role of prostaglandins in producing cerebrovasodilation during hypercapnia was tested in goats. Cerebral blood flow (CBF) changes with increasing arterial PCO2 were measured before and after prostaglandin synthesis inhibition with indomethacin or ibuprofen. Both drugs produced significant decreases in CBF under control anesthetized conditions but had no significant effect on the cerebrovascular response to increased arterial PCO2. The effects of direct intracerebrovascular infusion of prostaglandin E 2 (PGE2), prostaglandin F2α (PGF2α) and prostacyclin were also measured. In the dose range tested (0.1–1 ug/min) PGF2α had no significant effect on cerebral blood flow (CBF). Both PGE2 and PGI2 produced an increase in CBF and the increase produced by PGI2 was significantly greater than that produced by PGE2. The effectiveness of each compound in producing cerebrovascular changes is consistent with the endogenous distribution of prostaglandins within the brain. These results suggest that prostaglandins, particularly PGI1, may be important in modulating cerebrovascular tone but have no role in increasing CBF during hypercapnia.

Effects of indomethacin on cerebral blood flow and oxygen consumption in barbiturate-anesthetized Normocapnic and hypercapnic rats.

Although results obtained in baboons and rats have demonstrated that the fatty acid cyclo-oxygenase inhibitor indomethacin reduces cerebral blood flow (CBF) under control conditions and markedly attenuates the CBF response to hypercapnia, nonconfirmatory results have been obtained in rabbits and cats. Since these latter studies were carried out under barbiturate anesthesia, we tested the effect of indomethacin (10 mg kg-1) on CBF and cerebral oxygen consumption in rats anesthetized with 150 mg kg-1 of phenobarbital. At normocapnia the barbiturate reduced CBF, measured with a 133Xe modification of the Kety-Schmidt technique, to about 50% of nitrous oxide control values as previously determined with a similar technique. At this CBF level, indomethacin induced a small, albeit highly significant decrease in CBF. We suggest that a reduction of this magnitude will escape detection with some CBF techniques in current use. Indomethacin induced a highly significant decrease in CBF during hypercapnia, demonstrating that the barbiturate does not eliminate the effect of indomethacin on CO2 responsiveness. The magnitude of the reduction in CO2 response was so large that is should be detected with most methods for measuring CBF. A comparison with previous data on animals under 70% N2O demonstrated that phenobarbital reduced the CO2 responsiveness. defined as the ratio deltaCBF/deltaPCO2, to 39% of that observed under nitrous oxide analgesia. With both types of anesthesia, indomethacin curtailed the CO2 responsiveness 4- to 5-fold.

Cerebrovascular reactivity and metabolism after subarachnoid hemorrhage in baboons.

Subarachnoid hemorrhage (SAH) was induced in baboons by puncturing the middle cerebral artery. Four to seven days later cerebral blood flow (CBF) responses to changing PaCO2 and to intracarotid infusion of 1.0, 2.5 and 5.0 micrograms of 5-hydroxytryptamine (5-HT)/kg/min were studied using the intracarotid 133xenon clearance technique. Indices of cerebral metabolism were determined by measuring arterio-venous differences for oxygen, pyruvate, lactate and glucose. The results were compared with those from sham-operated baboons. In the sham-operated group normal CO2 reactivity was seen, and 5-HT infusion did not produce any significant change in CBF or cerebral metabolism. By contrast, the group in which SAH was induced showed a significant decrease in CBF and cerebral oxygen utilization, and attenuated CO2 reactivity.

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.