Reduction In Cerebral Blood Volume Research Articles

Alpha-2 agonists in neuroanesthesia

La dexmedetomidina se usó para sedación inicialmente en unidades de cuidados intensivos. Sin embargo, sus efectos sedantes, analgésicos y ansiolíticos sin alteración de la función ventilatoria, permiten ampliar su uso en cirugía como anestésico intravenoso. La literatura reporta su utilidad en poblaciones quirúrgicas definidas, pero aún faltan estudios que respalden su utilización en todos los escenarios de la anestesia total intravenosa (TIVA). El propósito de la actual revisión es describir el papel de la dexmedetomidina en la misma.Se realizó la búsqueda de literatura en las bases de datos referenciales de PubMed, Medline, EMBASE, Cochrane y LILACS. Fue ampliada según la bibliografía encontrada en los artículos inicialmente revisados y analizadosDexmedetomidine was used initially for sedation in intensive care units. However, because of its sedative, analgesic and anti-anxiety effects and the fact that it does not alter ventilatory function, its use may be expanded as an intravenous agent in surgery. There are reports in the literature about its effective use in specific surgical populations, although further studies are required in order to support its use in all situations where total intravenous anesthesia (TIVA) is applied. The purpose of this review is to describe the role of dexmedetomidine in this form of anesthesia.A literature search was conducted in PubMed, Medline, EMBASE, Cochrane and LILACS. The search was expanded based on the references found in the articles repor los autores; la búsqueda fue hecha bajo los términos MeSH incluidos en las palabras claves.

Determination of kinetic rate constants for 2-[18F]fluoro-2-deoxy-D-glucose and partition coefficient of water in conscious macaques and alterations in aging or anesthesia examined on parametric images with an anatomic standardization technique.

Kinetic rate constants for 2-[18F]fluoro-2-deoxy-d-glucose (FDG) and the tissue-blood partition coefficient of water were determined using dynamic positron emission tomography in conscious macaques, and alterations in these parameters in aging or anesthesia were also examined. The parameters were estimated on a pixel-by-pixel basis using an anatomic standardization technique; group differences were then examined on the parametric images from the young, aged, and anesthesia groups. For the conscious condition, seven young and seven aged male rhesus macaques were used; six young male rhesus macaques were used for the isoflurane anesthesia condition. H2 15O and FDG were used as tracers. The kinetic parameters were estimated by a nonlinear least-square fitting procedure with compartment models including terms for the cerebral blood volume (CBV) and time delay of the input function. Cerebral blood flow (CBF) and cerebral metabolic rate of glucose (CMRglc) were also calculated from the estimated parameters. In the aged group, glucose phosphorylation was decreased more than glucose transport, and the occipital cortex was the most affected region where reduction in CBV, CMRglc, and CBF were also observed. In the anesthesia group, glucose transport was decreased; however, glucose phosphorylation was not affected except for the occipital pole. The occipital cortex was also the most affected region. The tissue-blood partition coefficient of water was decreased globally.

Quantitative perfusion imaging by multi-slice CT in stroke patients

Evaluation of a parametric deconvolution algorithm (DA) in the diagnostic assessment of stroke patients by multi- slice spiral computed tomography (MS-CT). 52 patients (age range 34 - 89 years) with clinically suspected acute ischemia of one hemisphere and no infarct demarcation on plain cerebral CT underwent CT perfusion (CTP), performed on average 3.4 hours after the onset of symptoms by using MS-CT (4 x 8 mm scan volume). Using a DA-based software module, perfusion images of the cerebral blood perfusion (CBP), cerebral blood volume (CBV) and mean transit time (MTT) were calculated and assessed by two readers for visually apparent perfusion abnormalities. Amount and extension of perfusion disturbances were measured and correlated with the outcome. Of 44 patients, in whom perfusion maps could be generated, territorial infarction was confirmed by follow-up in 22 subjects. With a sensitivity of 95 % ischemia could be detected on MTT-maps (CBP 91 %, CBV 77 %). Specificity was highest (100 %) for CBV-maps. Patients with infarction showed significant (p < 0.001) reduction of CBP (10.7 vs. 38.3 ml/100 ml/min), CBV (1.3 vs. 2.3 ml/100 ml) and prolongation of MTT (12.3 vs. 4.3 s) compared to the contralateral hemisphere, whereas in patients without infarction no significant changes were found. Extension of CBV reduction showed the best correlation (r = 0.82) with final infarct volume. The DA-based CTP protocol evaluated in this study is a suitable tool for the early identification and quantification of acute cerebral ischemia.

Volume-targeted therapy of increased intracranial pressure.

Fluid exchange across the intact blood-brain barrier (BBB) is counteracted by the low permeability to crystalloids (mainly Na+ and Cl-) combined with the high osmotic pressure (5,700 mm Hg) on both sides of the BBB. If the BBB is disrupted transcapillary water transport will be determined by the differences in hydrostatic and colloid osmotic pressure between the intra- and extracapillary compartments. Under these pathological conditions pressure autoregulation of cerebral blood flow is likely to be impaired and intracapillary hydrostatic pressure will depend on variations in systemic blood pressure. The volume targeted "Lund concept" can be summarized under four headings: A. Reduction of stress response and cerebral energy metabolism: B. Reduction of capillary hydrostatic pressure; C. Maintenance of colloid osmotic pressure and control of fluid balance: D. Reduction of cerebral blood volume. The efficacy of the protocol has been evaluated in experimental and clinical studies regarding the physiological and biochemical (utilizing intracerebral microdialysis) effects and the clinical experiences have been favourable.

The Effects of Sustained Hyperventilation on Regional Cerebral Blood Volume in Thiopental-Anesthetized Rats

Sustained hyperventilation has a time-limited effect on cerebrovascular dynamics. We investigated whether this effect was similar among brain regions by measuring regional cerebral blood volume (CBV) with steady-state susceptibility contrast magnetic resonance imaging during 3 h of hyperventilation. Regional CBV was determined in nine thiopental-anesthetized, mechanically-ventilated rats every 30 min in the dorsoparietal neocortex, the corpus striatum, and the cerebellum. The corpus striatum was the only brain region showing a stable reduction in CBV during the hypocapnic episode (PaCO(2), 24 +/- 3 mm Hg). In contrast, neocortex and, to a lesser extent, cerebellum exhibited a progressive return toward normal values despite continued hypocapnia. No evidence of a rebound in CBV was found on return to normal ventilation in the three brain regions. We conclude that sustained hyperventilation can lead to an uneven change in the reduction of CBV, possibly because of differences of brain vessels in their sensitivity to extracellular pH. Our results in neocortex confirm the transient effect of sustained hyperventilation on cerebral hemodynamics. Sustained hyperventilation has a transient effect in decreasing cerebral blood volume (CBV). Using susceptibility contrast magnetic resonance imaging in thiopental-anesthetized rats, we found differences between brain regions in their transient CBV response to sustained hyperventilation.

Volume-targeted therapy of increased intracranial pressure: the Lund concept unifies surgical and non-surgical treatments.

Opinions differ widely on the various treatment protocols for sustained increase in intracranial pressure (ICP). This review focuses on the physiological volume regulation of the intracranial compartments. Based on these mechanisms we describe a protocol called 'volume-targeted' ('Lund concept') for treatment of increased ICP. The driving force for transcapillary fluid exchange is determined by the balance between effective transcapillary hydrostatic and osmotic pressures. Fluid exchange across the intact blood-brain barrier (BBB) is counteracted by the low permeability to crystalloids (mainly Na+ and Cl-) combined with the high osmotic pressure (5500 mmHg) on both sides of the BBB. This contrasts to most other capillary regions where the osmotic pressure is mainly derived from the plasma proteins (approximately 25 mmHg). Accordingly, the level of the cerebral perfusion pressure (CPP) is of less importance under physiological conditions. In addition cerebral intracapillary hydrostatic pressure (and cerebral blood flow) is physiologically tightly autoregulated, and variations in systemic blood pressure are generally not transmitted to these capillaries. If the BBB is disrupted, transcapillary water transport will be determined by the differences in hydrostatic and colloid osmotic pressure between the intra- and extracapillary compartments. Under these pathological conditions, pressure autoregulation of cerebral blood flow is likely to be impaired and intracapillary hydrostatic pressure will depend on variations in systemic blood pressure. The volume-targeted 'Lund concept' can be summarized under four headings: (1) Reduction of stress response and cerebral energy metabolism; (2) reduction of capillary hydrostatic pressure; (3) maintenance of colloid osmotic pressure and control of fluid balance; and (4) reduction of cerebral blood volume. The efficacy of the protocol has been evaluated in experimental and clinical studies regarding the physiological and biochemical (utilizing intracerebral microdialysis) effects, and the clinical experiences have been favorable.

Transient vasodilatory effects of adrenomedullin on cerebral parenchymal microvessels in cats

We studied the effects of adrenomedullin, structural homology of calcitonin gene-related peptide (CGRP), on the cerebral parenchymal microvessels in cats by our photoelectric method. Adrenomedullin significantly increased cerebral blood volume (CBV) at 0.5 and 1 min after intracarotid injection (0.01–1 nmol/kg, maximum; +0.71 vol% for 0.1 nmol/kg adrenomedullin). Adrenomedullin antagonist, adrenomedullin 22–52 (0.01–10 nmol/kg), caused no significant changes in CBV and mean arterial blood pressure. Preinjection of 10 nmol/kg adrenomedullin 22–52 blocked the vasodilatory effect of 0.01 nmol/kg adrenomedullin ( P<0.05). Pretreatment of 1 nmol/kg CGRP 8–37, which has antagonistic activity against CGRP, also inhibited the vasodilatation of adrenomedullin. The degree of CBV reduction after adrenomedullin 22–52 injection was greater than that after CGRP 8–37 injection. Adrenomedullin has no major role in the maintenance of resting tone of intracerebral parenchymal vessels. Intravascularly administered adrenomedullin dilates cortical microvessels mainly through the specific adrenomedullin receptor.

Comparative evaluation of the effects of indomethacin and ibuprofen on cerebral perfusion and oxygenation in preterm infants with patent ductus arteriosus

Objective: To compare the effects on cerebral perfusion and oxygenation of intravenous ibuprofen and indomethacin as treatment for patent ductus arteriosus in preterm infants. Study design: Sixteen infants receiving mechanical ventilation (< 31 weeks gestation) with patent ductus arteriosus received either 0.2 mg/kg indomethacin ( n = 8) or 10 mg/kg ibuprofen ( n = 8) infused over 1 minute. Near-infrared spectroscopy was used to measure changes in cerebral blood volume and in oxidized cytochrome oxidase concentration. Cerebral blood flow velocity in the pericallosal artery was measured using Doppler ultrasonography. Results: Indomethacin caused a significant reduction of CBV (maximal changes in cerebral blood volume: −320 ± 171 μL/100 gm) and, in four of eight patients, a fall in oxidized cytochrome oxidase concentration (maximal change in oxidized cytochrome oxidase concentration in the eight patients: −0.68 ± 0.98 μmol/L, NS). Cerebral blood flow velocity fell significantly. Ibuprofen caused no significant reduction of cerebral blood volume, oxidized cytochrome oxidase concentration, or cerebral blood flow velocity, whereas a significant increase of cerebral blood volume (+207 ± 200 μL/100 gm) was observed after 60 minutes. Ductus closure was seen in six of eight infants after the first dose of indomethacin and in five of eight infants after the first dose of ibuprofen. The therapeutic cycle involved administration of a second and third dose, provided no side effects occurred. Treatment was effective in all infants. Conclusion: Compared with indomethacin, treatment with ibuprofen does not significantly reduce cerebral perfusion and oxygen availability; the observed increase in cerebral blood volume requires further investigation. ( J Pediatr 1997;131:549-54)

Influence of various ventilatory parameters on NIR reflexion spectroscopy based cerebral oxygen measurements. An experimental animal study.

Sustained elevation of intracranial pressure (ICP) is commonly found as a sequel to severe head injury and has been demonstrated to adversely affect both cerebral metabolism (Bouma 91, Cruz 90), hemodynamics (Obrist 84) and outcome (Gopinath 94, Marshall 79) in this group of patients. Hyperventilation is in wide use as one of the immediate therapeutic measures in the treatment of head injury to control intracranial hypertension by reduction of cerebral blood volume (CBV) (Cruz 90, Greenberg 78, Owen-Reece 94, Pryds 90, Thoresen 79). However, questions still remain regarding the effects of carbon dioxide tension on cerebral oxydative metabolism in brain injured patients, especially with potential impairment of cerebrovascular reactivity and altered hemodynamics (Cruz 90, Harper 65, Langfitt 65, Muizelaar 91, Obrist 84, Sutton 90). The benefits of lowering raised ICP may sometimes be compromised by adverse effects on cerebral oxygenation (Cruz 90, Muizelaar 91, Sutton 90). The value of NIRS based monitoring of cerebral hemodynamics and oxygenation has already been demonstrated (Höper 94, McCormick 91, Owen-Reece 94, Steinberg 96, Wray 88). However, no conclusive data exist from a controlled experimental study addressing the effects of pCO2 variation on cerebral tissue oxygenation during intracranial hypertension. Quantification of these effects is of importance, since clinical decision making would be greatly facilitated by definition of a therapeutic range, within which pCO2 can be safely varied according to individual requirements without causing cerebral desaturation. We therefore designed this experimental study to elucidate the impact of different ventilatory parameters on cerebral tissue oxygen saturation using a new reflectance spectroscopic system (Multiscan OS 10 (Steinberg 96)) under controlled baseline conditions and during ICP elevation.KeywordsIntracranial HypertensionMean Standard DeviationCerebral Blood VolumeCerebral OxygenationSevere Head InjuryThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Effects of ventricular arrhythmia on the cerebral microcirculation in cats.

To test the widely believed but poorly proved hypothesis that the cerebral symptoms observed during ventricular arrhythmia are caused by a reduced cerebral blood supply, we examined the effects of single and multiple ectopic ventricular beats (or ventricular tachycardia of short duration) on the cerebral microcirculation. Six anesthetized cats were used. Ectopic ventricular systoles of various sequences were produced by electrically stimulating the ventricle through a bipolar needle-type electrode for 1 to 50 times at a rate of 300/min. The local cerebral blood volume (CBV) and blood flow (CBFLD) in the cortex were measured continuously employing the photoelectric and laser Doppler methods. CBV reflects the cumulative dimensions of the cerebrocortical microvessels. Ectopic ventricular contractions, as confirmed by electrocardiograms, always reduced the CBV and arterial blood pressure in a total of 104 attempts. The CBV reductions ranged from 0.20 +/- 0.03 vol% for a single ectopic beat to approximately 0.6-0.8 vol% for runs of 8 or more beats. The CBFLD reductions measured with the laser Doppler flowmeter were 10-35%. The reductions in CBV and CBFLD during the ventricular arrhythmia could be attributed to the abrupt and marked reductions in arterial blood pressure. Runs of ectopic ventricular beats have significant effects on the cerebral microcirculation, whether clinically apparent or not.

Y a-t-il encore une place pour l'hypocapnie profonde de routine en chirurgie intracrânienne ?

Deliberate hypocapnia during the anaesthetic management of the patient undergoing craniotomy has become an accepted standard of care. However there has been a resurgence of interest, in how hypocapnia should be applied in intra- and extra-operative settings. There are three possible therapeutic effects of hypocapnia, namely, (a) reduction of brain bulk through a reduction in cerebral blood volume, with a decrease cerebral blood flow; (b) developing an « inverse stealby redistribution of blood from normal to ischaemic regions and (c) acting to offset cerebral acidosis by increasing pH in the extracellular space. In anaesthetic intraoperative practice, hypocapnia is used as a specific treatment of, or prophylaxis against, intracranial hypertension during induction of anaesthesia and the period before dural exposure. More commonly, hypocapnia is used for intraoperative brain relaxation (intracranial pressure = 0). Severe hypocapnia (< 20 mmHg) may result in cerebral production of lactate; however no studies have shown that a Pa co 2 in the range of 23–28 mmHg has deleterious effects. Recent studies in head-injured patients suggest that routine long-term hyperventilation, without an objective index of cerebral flow/metabolism coupling, may place the brain at risk for adverse outcome. The few data available for intraoperative management suggest that Pa co 2 figures of 30–35 mmHg result in acceptable operating conditions. Unless otherwise specifically indicated by surgical conditions or cerebral flow/metabolism coupling (e.g. jugular O2 saturation), routine application of profound (Pa co 2 < 28–30 mmHg) hyperventilation should probably be avoided and its use needs reevaluation.

CEREBRAL OXYGENATION AND CEREBRAL BLOOD VOLUME DURING AMINOPHYLLINE TREATMENT IN PREMATURE NEWBORNS: QUANTITATIVE MEASUREMENT BY NEAR INFRARED SPECTROSCOPY

Aminophylline is commonly used for treatment of apnea and to permit weaning from ventilation in preterm newborns. Previous reports have indicated that it may cause cerebral vasoconstriction and reduction in cerebral blood flow (CBF) and cerebral blood volume (CBV). It is not known whether such reduction in CBF/CBV results in significant reduction in cerebral oxygenation. The purpose of this study was to evaluate the effect of aminophylline therapy on CBV and cerebral oxygenation using near infrared spectroscopy (NIRS Hamamatsu 500), Aminophyllinc (6.5 mg/kg) was given intravenously prior to weaning from the ventilator to 19 stable preterm infants (mean g.a.: 32 wks) with hyaline membrane disease. CBV, Hb diff (HbO2-Hb), deoxyhemoglobin (Hb) and cytochrome oxidase (CtO2) were measured using NIRS before and after aminophylline infusion. Continuous recordings of mean arterial pressure (MAP), tcpCO2 and tcpO2 were correlated with NIRS data. There was a marked fall in CBV after aminophylline infusion in 15 newborns with no significant reduction in tcpCO2. Despite reduction in CBV, cerebral oxygenation (HbD, CtO2) improved in stable preterm newborns.

Constriction/Dilatation of the Cerebral Microvessels by Intravascular Endothelin-1 in Cats

The effects of intracarotidly injected endothelin (ET)-1 (0.01-3 nmol) on the local cerebral blood volume (CBV) in the parietotemporal cortex were examined by the photoelectric method in 17 anesthetized cats. CBV reflects the cumulative dimensions of the cerebral microvessels. Low doses of ET-1 (0.01 and 0.1 nmol) elicited mild but significant reductions in CBV without changes in the systemic arterial blood pressure (SABP). High doses of ET-1 (3 nmol) initially induced marked declines of CBV, which were attributable to the significant falls in SABP. CBV subsequently exhibited significant increases. The CBV increases were not secondary to the accompanying elevations of SABP, since they were unaffected by inhibition of the SABP changes after preinjection of BQ-123 (1 mg/kg), an ET antagonist specific to the ETA receptors. The CBV increases, however, were prevented by continuous administration of NG-mono-methyl-L-arginine (0.35 mg/kg/min), an inhibitor of nitric oxide synthesis, plus BQ-123. We conclude that while low doses of intravascular ET-1 constrict the cerebral microvessels, high doses of ET-1 dilate the cerebral microvessels through the induction of nitric oxide probably in the cerebrovascular endothelium.

Effects of sumatriptan on the cerebral intraparenchymal microcirculation in the cat.

1. Sumatriptan, a 5-hydroxytryptamine (5-HT)1-like receptor agonist, is effective against the headache of migraine. The effects of sumatriptan injected via the carotid artery on the cerebral microcirculation were studied in 10 anaesthetized cats. 2. The local cerebral blood volume (CBV), mean transit time of blood (MTT) and cerebral blood flow (CBF) in the parieto-temporal cortex were measured by a photoelectric method. CBV represents the cumulative dimensions of the cerebral microvessels. 3. Sumatriptan at 5 and 50 micrograms kg-1 had no significant effects on the CBV, MTT, CBF, and mean arterial blood pressure (MABP); 500 micrograms kg-1 of sumatriptan reduced the CBV, prolonged the MTT, and decreased the CBF (approximately -20%) without affecting the MABP. Sumatriptan, 5 mg kg-1, elicited transient reductions in CBV and CBF, which were attributable to the rapid and marked falls of MABP seen with this dose. 4. Thus, while a high dose of sumatriptan (500 micrograms kg-1) exhibits direct vasoconstrictor actions on the cerebral vessels, low doses of sumatriptan, within the therapeutic range, elicit no vasoconstriction. The data do not support a vasoconstrictor action of sumatriptan playing a primary role in reversing the headache of migraine.

Capillary Recruitment for Preservation of Cerebral Glucose Influx in Hypoglycemic, Preterm Newborns: Evidence for a Glucose Sensor?

Changes in cerebral blood volume (CBV) were investigated by means of near-infrared spectroscopy in 18 preterm newborns during treatment with intravenous bolus glucose. All newborns were breathing spontaneously, and their postnatal age was 2 hours. Blood glucose concentration ranged between 0.3 and 2.2 mmol/L. Cerebral blood volume began to decrease shortly after the glucose infusion was terminated, and steady state was obtained after approximately 3 minutes. The decrease in CBV averaged 0.15 mL/100 g (range 0.02 to 0.40 mL/100 g). Thereafter, CBV remained constant. Individual reductions in CBV were inversely related to the pretreatment concentration of glucose, whereas there was no relation between changes in CBV and alterations in blood gas values or in mean arterial blood pressure. It is suggested that previously unperfused capillaries are recruited to maintain the glucose transport into neurons of hypoglycemic, preterm newborns. The rapidity whereby vessels adjust to alterations in glucose levels indicates the existence of a cerebral glucose sensor.

Bilateral hemispheric reduction of cerebral blood volume and blood flow immediately after experimental cerebral hemorrhage in cats.

Acute cerebral circulatory changes following experimental cerebral hemorrhage were investigated in eight cats. The cerebral hemorrhage was produced in the right basal ganglia by introducing arterial blood via a thin catheter, using the systemic arterial blood pressure of the cat as a driving force. Local cerebral blood volume was measured continuously in the bilateral parietotemporal cortexes employing photoelectric apparatuses. Carbon black dilution curves were recorded from the regions, and the mean transit time of blood was calculated. Local cerebral blood flow was estimated from mean transit time and cerebral blood volume. Intracranial pressure was monitored continuously in the right parietal epidural space. Five minutes after cerebral hemorrhage, intracranial pressure increased by 24.0 +/- 6.1 mm Hg, while mean arterial blood pressure increased by only 2.9 +/- 2.0 mm Hg. Cerebral blood volume decreased by 1.60 +/- 0.24 vol% in the hemorrhagic and 1.14 +/- 0.30 vol% in the nonhemorrhagic hemisphere. Cerebral blood flow decreased by 30.0 +/- 4.5 ml/100 g brain/min in the hemorrhagic (initially 64.5 +/- 13.6) and by 30.3 +/- 7.5 ml/100 g brain/min in the nonhemorrhagic (initially 60.9 +/- 6.9) hemisphere. Increased intracranial pressure appeared to be the main cause of the observed cerebral blood volume/flow reduction shortly after experimental hemorrhage in the basal ganglia. Several other factors and mechanisms involved are discussed.

Cerebral perfusion pressure: a hemodynamic mechanism of mannitol and the postmannitol hemogram.

Sixteen patients each received infusions of 1 g of mannitol per kg over 5 to 10 minutes, and serial determinations of intracranial pressure (ICP), systemic arterial blood pressure (SABP), central venous pressure, cerebral perfusion pressure (CPP), hematocrit, hemoglobin, serum Na+, K+, osmolarity, and fluid balance were carried out for 4 hours. Urine output was replaced volume for volume with 5% dextrose in 0.45% NaCl solution. We tested the hypothesis that patients with high (greater than or equal to 70 torr) CPP would respond less well to mannitol by either ICP or CPP criteria than patients with low (less than 70 torr) CPP. The rationale for this hypothesis was based upon the association of low CPP with autoregulatory vasodilatation, whereas high CPP is associated with vasoconstriction. If mannitol should work by a vasoconstriction mechanism, the ICP effects should be most apparent under conditions of low CPP. Those patients with CPP greater than or equal to 70 torr responded relatively poorly to mannitol, with ICP decreasing from 25 +/- 4 to 17 +/- 5 (SE) mm Hg at 45 minutes postinfusion. Patients with CPP less than 70 responded with ICP declining from 35 +/- 5 to 13 +/- 4 mm Hg. The initial SABP was 81 +/- 5 mm Hg in the CPP less than 70 group and immediately rose to 90 +/- 7 at 15 minutes postmannitol. The SABP increase correlated with ICP (r = -0.40, P less than 0.01), but not when CPP greater than or equal to 70. SABP was significantly higher in the latter group (105 +/- 6) and increased to 107 +/- 8 postmannitol. The ICP decrease began immediately with the SABP increase. No mannitol "rebound" occurred in these patients. Measures of acute volume expansion all correlated with ICP (Na+, r = -0.67, P less than 0.001; hematocrit, r = -0.27, P less than 0.01; serum osmolarity, r = 0.32, P less than 0.05) when CPP less than 70 torr. None correlated with ICP when CPP greater than or equal to 70. These data suggest that mannitol infusion is at least partly dependent upon hemodynamic mechanisms that allow vasoconstriction to occur with reduction in cerebral blood volume and that little may be gained by using mannitol when CPP greater than or equal to 70 either by SABP, ICP, or CPP criteria because vasoconstriction is already nearly maximal. This mechanism is not exclusive of other potential mechanisms of action. Mannitol "rebound" may be a function of net dehydration, hemoconcentration, and SABP decline.

Mannitol causes compensatory cerebral vasoconstriction and vasodilation in response to blood viscosity changes.

There is no proof that osmotic agents such as mannitol lower intracranial pressure (ICP) by decreasing brain water content. An alternative mechanism might be a reduction in cerebral blood volume through vasoconstriction. Mannitol, by decreasing blood viscosity, would tend to enhance cerebral blood flow (CBF), but the cerebral vessels would constrict to keep CBF relatively constant, analogous to pressure autoregulation. The cranial window technique was used in this study to measure the pial arteriolar diameter in cats, together with blood viscosity and ICP changes after an intravenous bolus of 1 gm/kg of mannitol. Blood viscosity decreased immediately; the greatest decrease (23%) occurred at 10 minutes, and at 75 minutes there was a "rebound" increase of 10%. Vessel diameters decreased concomitantly, the largest decrease being 12% at 10 minutes, which is exactly the same as the 12% decrease in diameter associated with pronounced hyperventilation (PaCO2 30 to 19 mm Hg) in the same vessels; at 75 minutes vessel diameter increased by 12%. With hyperventilation, ICP was decreased by 26%; 10 minutes after mannitol was given, ICP decreased by 28%, and at 75 minutes it showed a rebound increase of 40%. The correlation between blood viscosity and vessel diameter and between vessel diameter and ICP was very high. An alternative explanation is offered for the effect of mannitol on ICP, the time course of ICP changes, "rebound effect," and the absence of influence on CBF, all with one mechanism.

LOCAL CEREBRAL BLOOD VOLUME IN HEAD-INJURED PATIENTS. DETERMINATION BY EMISSION COMPUTED TOMOGRAPHY OF 99mTc-LABELED RED CELLS

✓ Local cerebral blood volume (CBV) was mapped in 10 normal subjects and in 30 patients after head injury. In normal subjects, the mean CBV was 4.34 ml/100 gm. The coefficient of variation was 12% for the group mean, and 3% for values obtained in duplicate studies of individuals. Patients with head injuries were divided into three groups according to the stage of their illness: acute illness, early recovery, and later recovery. Averages of mean CBV were within one standard deviation of normal. In contrast, consistent changes were found in serial studies of the mean CBV in the same patient. Compared to recovery values, levels of mean CBV measured soon after injury were reduced, largely at the expense of the gray-matter compartment. In five adults with predominantly unilateral lesions, there was an average early reduction in mean CBV and cerebral blood flow of 15% and 36%, respectively. In three children with diffuse brain swelling, there was an average early mean CBV reduction of 12%; a single child had ea...

Local cerebral blood volume in head-injured patients. Determination by emission computed tomography of 99mTc-labeled red cells.

Local cerebral blood volume (CBV) was mapped in 10 normal subjects and in 30 patients after head injury. In normal subjects, the mean CBV was 4.34 ml/100 gm. The coefficient of variation was 12% for the group mean, and 3% for values obtained in duplicate studies of individuals. Patients with head injuries were divided into three groups according to the stage of their illness: acute illness, early recovery, and later recovery. Averages of mean CBV were within one standard deviation of normal. In contrast, consistent changes were found in serial studies of the mean CBV in the same patient. Compared to recovery values, levels of mean CBV measured soon after injury were reduced, largely at the expense of the gray-matter compartment. In five adults with predominantly unilateral lesions, there was an average early reduction in mean CBV and cerebral blood flow of 15% and 36%, respectively. In three children with diffuse brain swelling, there was an average early mean CBV reduction of 12%; a single child had early increased mean CBV at a time when intracranial pressure was high. Greater changes were seen in local CBV on individual sections. There were mixed zones of hypervolemia and hypovolemia in regions of infarction and intracerebral hematoma. Subdural hematomas had consistent medial margins of increased local CBV, representing dilated blood vessels of the underlying cortex. The presence and displacement of this hypervolemic zone were sensitive indicators of persistent subdural collection and mass effect, even when the collection was lucent to x-ray computed tomography.