Protective effect of the 5-lipoxygenase inhibitor AA-861 on cerebral edema after transient ischemia

1996 ◽  
Vol 85 (1) ◽  
pp. 112-116 ◽  
Author(s):  
Mustafa K. Baskaya ◽  
Yingan Hu ◽  
David Donaldson ◽  
Mary Maley ◽  
A. Muralikrishna Rao ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Specific Gravity ◽  
Cerebral Edema ◽  
Lipoxygenase Inhibitor ◽  
Transient Ischemia ◽  
Edema Formation ◽  
Content Type ◽  
Brain Levels ◽  
Significant Difference

✓ This study examined the effect of AA-861, a specific 5-lipoxygenase inhibitor, on brain levels of leukotriene C4 (LTC4) and correlated any changes with changes in edema formation and cerebral blood flow (CBF) after transient ischemia in gerbils. Brain levels of LTC4 were observed to be increased at 1, 2, and 6 hours of reperfusion following 20 minutes of occlusion. At 2 hours of reperfusion, a pretreatment dose of 1000 mg/kg of AA-861 was required to inhibit more than 90% of the reperfusion-induced increases in brain LTC4. At this dose, inhibition of LTC4 production was observed at 2 and 6 hours of reperfusion. The specific gravity of both the cortex and subcortex was decreased at 6 hours of reperfusion after 20 minutes of occlusion. At 2 hours of reperfusion, no significant difference was observed in the specific gravity of the cortex and subcortex regions of gerbils pretreated with AA-861 or with vehicle, but at 6 hours of reperfusion significant positive differences were observed. Cerebral blood flow decreased to approximately 10% of preocclusion values during occlusion and returned to near-preocclusion values after 10 minutes of reperfusion. No significant differences were observed in regional CBF in the AA-861- and vehicle-pretreated gerbils during reperfusion. These findings indicate that LTC4 production after transient cerebral ischemia may be an important contributor to the development of cerebral edema and that CBF does not mediate the LTC4-involved development of edema.

Influence of changes in arterial pCO2 on cerebral blood flow and metabolism during high-dose barbiturate therapy in dogs

1981 ◽  
Vol 54 (5) ◽  
pp. 615-619 ◽  
Author(s):  
Neal F. Kassell ◽  
Patrick W. Hitchon ◽  
Mary K. Gerk ◽  
Martin D. Sokoll ◽  
Todd R. Hill
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
High Dose ◽  
Sodium Thiopental ◽  
Arterial Pco2 ◽  
Content Type ◽  
Cerebral Vasoconstriction ◽  
Significant Difference ◽  
Before And After ◽  
High Doses

✓ In 13 dogs the response of the cerebral circulation to changes in PaCO2 ranging from 20 to 60 torr was studied before and after administration of high doses of sodium thiopental. Infusion of sufficient barbiturate to produce 30- to 60-second burst suppression in the electroencephalogram was associated with a profound degree of cerebral vasoconstriction, equivalent to that produced by hypocapnia with PaCO2 = 20 torr. Furthermore, once sodium thiopental was administered, no significant difference in cerebral blood flow (CBF) or vascular resistance (CVR) was noted between PaCO2 of 30 and 20 torr. However, changes of approximately 15% in CBF and 30% in CVR were noted between PaCO2 at 40 and 20 torr. These data suggest that hyperventilation of PaCO2 of less than 30 torr may not effectively increase the degree of cerebral vasoconstriction in these circumstances.

Cerebral effects of isovolemic hemodilution with a hypertonic saline solution

1985 ◽  
Vol 63 (6) ◽  
pp. 944-948 ◽  
Author(s):  
Michael M. Todd ◽  
Concezione Tommasino ◽  
Suzanne Moore
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Specific Gravity ◽  
Hypertonic Saline ◽  
Normal Saline ◽  
Hypertonic Saline Solution ◽  
Tissue Samples ◽  
Isovolemic Hemodilution ◽  
Content Type ◽  
Fine Print

✓ In view of a growing interest in the resuscitative use of hypertonic saline solutions, the authors have examined the cerebral effects of isovolemic hemodilution carried out over 1 hour (hematocrit decreased from 40% to 20%, stable arterial and right arterial pressures), using a hypertonic lactated Ringer's solution (HT-LR:Na+ 252 mEq/liter, osmolality 480 mOsm/liter). Experiments were carried out in anesthetized ventilated rabbits. Measured variables included cerebral blood flow (using the H2 clearance method), intracranial pressure (ICP), the electroencephalogram, spinal cord and skeletal muscle water content (%H2O), and the specific gravity of small (10- to 30-mg) tissue samples taken from different areas of the left hemisphere (including the cortex, thalamus, internal capsule, and hippocampus). The changes produced by HT-LR were compared with those seen in both undiluted control animals and in rabbits hemodiluted with normal saline (Na+ 155 mEq/liter, osmolality 310 mOsm/liter). The results demonstrate that hemodilution with HT-LR leads to the expected increases in serum Na+ and osmolality (158 ± 6 mEq/liter and 320 ± 5 mOsm/kg, respectively, mean ± standard deviation) and that these were accompanied by reductions in the %H2O of all cerebral and extracerebral tissues, increases in the specific gravity of all tissue regions studied, and a decrease in ICP (1.9 ± 0.7 mm Hg). By contrast, rabbits with hemodilution by normal saline showed no changes in either %H2O or specific gravity, but had significant increases in ICP (3.3 ± 1.3 mm Hg). Cerebral blood flow increased in all animals hemodiluted with either HT-LR or normal saline by a combined average of +29 ml/100 gm/min. Although these studies were performed in neurologically normal animals, the combination of cerebral changes seen with HT-LR (cerebral dehydration, less peripheral edema, decreased ICP but with increased cerebral blood flow) suggests that this approach may have some advantages over the use of isotonic fluids, and may have some utility in the resuscitation of head-injured patients.

Relationship between hemispheric cerebral blood flow, central conduction time, and clinical grade in aneurysmal subarachnoid hemorrhage

1985 ◽  
Vol 62 (1) ◽  
pp. 25-30 ◽  
Author(s):  
Jacob Rosenstein ◽  
Alexander Dah-Jium Wang ◽  
Lindsay Symon ◽  
Mikio Suzuki
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Subarachnoid Hemorrhage ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Initial Slope ◽  
Conduction Time ◽  
Clinical Grade ◽  
Content Type ◽  
Significant Difference ◽  
Fine Print

✓ The relationship between central conduction time (CCT) and hemispheric cerebral blood flow (CBF) has been examined in 20 patients presenting with subarachnoid hemorrhage. A total of 63 combined CCT/CBF recordings were performed at various times throughout the hospital course of these patients, and the findings were correlated to clinical status. The initial-slope index of the CBF (CBFisi) was found to correlate well with clinical grade, and a gradation in flow was noted between the different neurological grades. Patients in Grades I and II (Hunt and Hess classification) had the highest flows (mean CBFisi = 47.2 ± 8.1); Grade III patients had intermediate flows (mean CBFisi = 39.6 ± 7.8); and Grade IV patients had the lowest flows (mean CBFisi = 32.0 ± 6.4). While CCT tended to become increasingly prolonged with worsening grade, a significant difference could not be demonstrated between Grade I, II, and III patients. Only when Grade IV status was reached was the CCT significantly prolonged. When CBFisi and CCT were examined, a threshold relationship was noted between CBFisi and CCT prolongation. At flow values above 30, little change was noted in CCT, and CCT remained in the normal range. However, at flow values below 30, CCT became increasingly prolonged as blood flow diminished. The degree of CCT prolongation appeared to be directly proportional to the degree of blood flow diminution at flows below threshold.

Experimental intracerebral hemorrhage: relationship between brain edema, blood flow, and blood-brain barrier permeability in rats

1994 ◽  
Vol 81 (1) ◽  
pp. 93-102 ◽  
Author(s):  
Guo-Yuan Yang ◽  
A. Lorris Betz ◽  
Thomas L. Chenevert ◽  
James A. Brunberg ◽  
Julian T. Hoff
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Basal Ganglia ◽  
Brain Edema ◽  
Time Course ◽  
Mass Effect ◽  
Edema Formation ◽  
Content Type ◽  
Bbb Permeability ◽  
Fine Print

✓ There have been few investigations of brain edema formation after intracerebral hemorrhage (ICH), despite the fact that mass effect and edema are important clinical complications. The present study was designed to investigate the time course for the formation and resolution of brain edema and to determine how changes in cerebral blood flow (CBF) and blood-brain barrier (BBB) permeability are temporally related to edema formation following ICH. Anesthetized adult rats received a sterile injection of 100 µl of autologous blood into the caudate nucleus. Water and ion contents were measured immediately, at 4 and 12 hours, and daily to Day 7 (10 time points, six rats at each time) after experimental ICH. The water content of the ipsilateral basal ganglia increased progressively (p < 0.002) over the first 24 hours, then remained constant until after Day 5, when the edema began to resolve. Edema was most severe in the tissue immediately surrounding the hemorrhage; however, it was also present in the ipsilateral cortex, the contralateral cortex, and the basal ganglia. Measurements of local CBF (using [14C]-iodoantipyrine) and BBB permeability (using [3H]-α-aminoisobutyric acid) were obtained in separate groups of six to eight rats at various time intervals between 1 and 48 hours after ICH. Cerebral blood flow was reduced to 50% of control at 1 hour, returned to control values by 4 hours, but then decreased to less than 50% of control between 24 and 48 hours after ICH. The BBB permeability increased significantly prior to the occurrence of significant edema in the tissue surrounding the clot. However, BBB permeability in the more distant structures remained normal despite the development of edema. These results demonstrate a time course for the formation and resolution of brain edema following ICH similar to that observed during focal ischemia. Brain edema forms in the immediate vicinity of the clot as a result of both BBB disruption and the local generation of osmotically active substances and then spreads to adjacent structures. While local ischemia, due to the mass effect of the hemorrhage, may play a role in producing cytotoxic and vasogenic edema, the release of toxic substances from the clot should also be considered. Since edema is nearly maximal by 24 hours after ICH, therapy directed at reducing edema formation must be instituted within the 1st day.

Regional cerebral blood flow studies following superficial temporal-middle cerebral artery anastomosis

1975 ◽  
Vol 43 (6) ◽  
pp. 706-716 ◽  
Author(s):  
M. Peter Heilbrun ◽  
O. Howard Reichman ◽  
Robert E. Anderson ◽  
Theodore S. Roberts
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Middle Cerebral Artery ◽  
Cerebral Artery ◽  
Regional Cerebral Blood Flow ◽  
Internal Carotid ◽  
Superficial Temporal Artery ◽  
Regional Cerebral Blood ◽  
Content Type ◽  
Significant Difference

✓ Regional cerebral blood flow (rCBF) studies were performed during the postoperative period on 16 patients with internal carotid occlusions and inaccessible stenoses, and middle cerebral artery occlusion and stenoses, who underwent superficial temporal artery-middle cerebral artery (STA-MCA) anastomoses. The intra-arterial xenon method with selective application of the xenon bolus through the internal carotid and the newly established superficial temporal channel has allowed comparison of the flow provided by the pathological input with flow through the new input. The results show that initial rCBF (rCBF1) was globally reduced in all patients to a mean of 28.4 ± 11.9 ml/100 gm/min at a mean pCO2 of 29.6 ± 9.55 mm Hg. Patients with transient ischemic attacks (TIA) and minor strokes with minimal residua (RIND) had a mean rCBF1 of 30.4 ± 11.6 ml/100 gm/min at a mean pCO2 of 30 ± 10 mm Hg, while patients with completed strokes had a mean rCBF1 of 25.0 ± 12.4 ml/100 gm/min at a mean pCO2 of 29.1 ± 8.8 mm Hg. There was no significant difference between these two groups. This finding suggests that in this small group of patients with TIA's and RIND's, the cause of the stroke is probably related more to decreased perfusion than embolus, and may explain why these patients' symptoms improve after STA-MCA anastomosis. The results of this study suggest that in addition to an inaccessible lesion, global or focal decreased rCBF is a necessary criterion in the definition of indications for intracranial revascularization procedures.

Early changes measured by magnetic resonance imaging in cerebral blood flow, blood volume, and blood-brain barrier permeability following dexamethasone treatment in patients with brain tumors

1999 ◽  
Vol 90 (2) ◽  
pp. 300-305 ◽  
Author(s):  
Leif Østergaard ◽  
Fred H. Hochberg ◽  
James D. Rabinov ◽  
A. Gregory Sorensen ◽  
Michael Lev ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Magnetic Resonance ◽  
Brain Tumors ◽  
Mr Imaging ◽  
Blood Volume ◽  
Cerebral Blood Volume ◽  
Clinical Effects ◽  
Content Type ◽  
Fine Print

Object. In this study the authors assessed the early changes in brain tumor physiology associated with glucocorticoid administration. Glucocorticoids have a dramatic effect on symptoms in patients with brain tumors over a time scale ranging from minutes to a few hours. Previous studies have indicated that glucocorticoids may act either by decreasing cerebral blood volume (CBV) or blood-tumor barrier (BTB) permeability and thereby the degree of vasogenic edema.Methods. Using magnetic resonance (MR) imaging, the authors examined the acute changes in CBV, cerebral blood flow (CBF), and BTB permeability to gadolinium-diethylenetriamine pentaacetic acid after administration of dexamethasone in six patients with brain tumors. In patients with acute decreases in BTB permeability after dexamethasone administration, changes in the degree of edema were assessed using the apparent diffusion coefficient of water.Conclusions. Dexamethasone was found to cause a dramatic decrease in BTB permeability and regional CBV but no significant changes in CBF or the degree of edema. The authors found that MR imaging provides a powerful tool for investigating the pathophysiological changes associated with the clinical effects of glucocorticoids.

Transcorneal stimulation of trigeminal nerve afferents to increase cerebral blood flow in rats with cerebral vasospasm: a noninvasive method to activate the trigeminovascular reflex

2002 ◽  
Vol 97 (5) ◽  
pp. 1179-1183 ◽  
Author(s):  
Basar Atalay ◽  
Hayrunnisa Bolay ◽  
Turgay Dalkara ◽  
Figen Soylemezoglu ◽  
Kamil Oge ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Cerebral Vasospasm ◽  
Trigeminal Nerve ◽  
Nerve Endings ◽  
Noninvasive Method ◽  
Direct Stimulation ◽  
Content Type ◽  
Fine Print ◽  
Stimulation Of

Object. The goal of this study was to investigate whether stimulation of trigeminal afferents in the cornea could enhance cerebral blood flow (CBF) in rats after they have been subjected to experimental subarachnoid hemorrhage (SAH). Cerebral vasospasm following SAH may compromise CBF and increase the risks of morbidity and mortality. Currently, there is no effective treatment for SAH-induced vasospasm. Direct stimulation of the trigeminal nerve has been shown to dilate constricted cerebral arteries after SAH; however, a noninvasive method to activate this nerve would be preferable for human applications. The authors hypothesized that stimulation of free nerve endings of trigeminal sensory fibers in the face might be as effective as direct stimulation of the trigeminal nerve. Methods. Autologous blood obtained from the tail artery was injected into the cisterna magna of 10 rats. Forty-eight and 96 hours later (five rats each) trigeminal afferents were stimulated selectively by applying transcorneal biphasic pulses (1 msec, 3 mA, and 30 Hz), and CBF enhancements were detected using laser Doppler flowmetry in the territory of the middle cerebral artery. Stimulation-induced changes in cerebrovascular parameters were compared with similar parameters in sham-operated controls (six rats). Development of vasospasm was histologically verified in every rat with SAH. Corneal stimulation caused an increase in CBF and blood pressure and a net decrease in cerebrovascular resistance. There were no significant differences between groups for these changes. Conclusions. Data from the present study demonstrate that transcorneal stimulation of trigeminal nerve endings induces vasodilation and a robust increase in CBF. The vasodilatory response of cerebral vessels to trigeminal activation is retained after SAH-induced vasospasm.

Effect of continuous postive-pressure ventilation (CPPV) on edema formation in dog lung

1975 ◽  
Vol 39 (4) ◽  
pp. 672-679 ◽  
Author(s):  
P. Caldini ◽  
J. D. Leith ◽  
M. J. Brennan
Keyword(s):  
Blood Flow ◽  
Pulmonary Arterial Pressure ◽  
Venous Pressure ◽  
Arterial Oxygen Tension ◽  
Lung Parenchyma ◽  
Arterial Oxygen ◽  
Morphometric Measurements ◽  
Edema Formation ◽  
Significant Difference ◽  
Pulmonary Arterial

The effect of CPPV on edema formation in lungs perfused at constant blood flow was studied in whole dogs and in isolated dog lungs. In intact animals, subjected to an increase in left atrial pressure relative to pleural pressure of 40 Torr, pulmonary shunts correlate inversely (r = -0.82) with the level of end-expiratory pressure (PEE). CPPV had no significant effect on total extravasation of liquid even though PEE higher than 20 Torr was effective in preventing liquid from accumulating in the airways. In isolated lobes, perfused at constant blood flow and at a venous pressure of zero, accumulation of liquid occurred when PEE was increased above 8–10 Torr. At comparable levels of pulmonary arterial pressure, an increase in PEE resulted in lesser accumulation of liquid than when pulmonary venous pressure was elevated. Morphometric measurements revealed no significant difference in the distribution of accumulated liquid within the lung parenchyma between lobes made edematous either by raising venous pressuure or by raising PEE. It would appear that CPPV, while beneficial in improving arterial oxygen tension in pulmonary edema, does not prevent extravasation of liquid in lungs perfused at constant blood flow. High levels of PEE appear to damage the lung by favoring accumulation of liquid in the extravascular spaces of the lung.

Improvement in cerebral blood flow and metabolism following subarachnoid hemorrhage in response to prophylactic administration of the hydroxyl radical scavenger, AVS, (±)-N,N′-propylenedinicotinamide: a positron emission tomography study in rats

2000 ◽  
Vol 92 (6) ◽  
pp. 1009-1015 ◽  
Author(s):  
Seiji Yamamoto ◽  
Weiyu Teng ◽  
Shigeru Nishizawa ◽  
Takeharu Kakiuchi ◽  
Hideo Tsukada
Keyword(s):  
Positron Emission Tomography ◽  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Emission Tomography ◽  
Radical Scavenger ◽  
Content Type ◽  
Prophylactic Administration ◽  
Positron Emission ◽  
Hydroxyl Radical Scavenger ◽  
Fine Print

Object. The hydroxyl radical scavenger (±)-N,N′-propylenedinicotinamide (AVS) has been shown to ameliorate the occurrence of vasospasm following experimental subarachnoid hemorrhage (SAH) and to reduce the incidence of delayed ischemic neurological deficits (DINDs) in patients with SAH. The authors investigated whether prophylactic administration of AVS could improve cerebral blood flow (CBF) and cerebral glucose utilization (CGU) following SAH in rats.Methods. Anesthetized rats were subjected to intracisternal injection of blood (SAH group) or saline (control group). Either AVS (1 mg/kg/min) or saline (vehicle group) was continuously injected into the rat femoral vein. Forty-eight hours later, positron emission tomography scanning was used with the tracers 15O-H2O and 18F-2-fluoro-d-glucose to analyze quantitatively CBF and CGU, respectively, in the frontoparietal and occipital regions (12 regions of interest/group).In SAH rats receiving only vehicle, CBF decreased significantly (p < 0.05, Tukey's test) and CGU tended to decrease, compared with values obtained in control (non-SAH) rats receiving vehicle. In rats that were subjected to SAH, administration of AVS significantly (p < 0.05, Tukey's test) improved CBF and CGU in both the frontoparietal and occipital regions compared with administration of vehicle alone.Conclusions. Prophylactic administration of AVS improves CBF and CGU in the rat brain subjected to SAH, and can be a good pharmacological treatment for the prevention of DINDs following SAH.

Serial measurement of regional cerebral blood flow in patients with SAH using 133Xe inhalation and emission computerized tomography

1984 ◽  
Vol 60 (5) ◽  
pp. 916-922 ◽  
Author(s):  
Bruce Mickey ◽  
Sissel Vorstrup ◽  
Bo Voldby ◽  
Helle Lindewald ◽  
Aage Harmsen ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Computerized Tomography ◽  
Cerebral Arteries ◽  
Three Dimensional ◽  
Neurological Deficits ◽  
Content Type ◽  
Serial Measurement ◽  
Regional Flow ◽  
Delayed Neurological Deterioration

✓ A noninvasive three-dimensional method for measuring cerebral blood flow (CBF), xenon-133 inhalation and emission computerized tomography, was used to investigate the CBF changes accompanying delayed neurological deterioration following subarachnoid hemorrhage (SAH). A total of 67 measurements were performed on 20 patients in Hunt and Hess' clinical Grades I to III in the first 21 days post SAH. Five patients with normal CBF tomograms on admission developed delayed neurological deficits in the 2nd week after hemorrhage, at which time repeat CBF tomograms in four patients revealed large areas of well defined regional flow decrease in the vascular territories of the anterior or middle cerebral arteries. Severe vasospasm was noted in three of these patients in whom arteriography was performed in the 2nd week post SAH. Diffuse bihemispheric CBF decreases were noted later in the course of delayed neurological deficits; however, measurements obtained soon after the onset of focal symptoms suggest that the only CBF decreases directly produced by vasospasm in Grade III patients are regional changes.

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