Effect of nimodipine on intracellular brain pH, cortical blood flow, and EEG in experimental focal cerebral ischemia

1986 ◽  
Vol 64 (4) ◽  
pp. 617-626 ◽  
Author(s):  
Fredric B. Meyer ◽  
Robert E. Anderson ◽  
Tony L. Yaksh ◽  
Thoralf M. Sundt
Keyword(s):  
Blood Flow ◽  
Cerebral Ischemia ◽  
Focal Cerebral Ischemia ◽  
Adjunctive Treatment ◽  
Control Group ◽  
Cortical Blood Flow ◽  
Content Type ◽  
Mca Occlusion ◽  
Brain Ph ◽  
Major Branch

✓ Intracellular brain pH, cortical blood flow, and electroencephalograms (EEG's) were recorded in severely and moderately ischemic regions in 10 control and 10 nimodipine-treated rabbits prior to and following major branch occlusion of the middle cerebral artery (MCA). Preocclusion cortical blood flow was 51 ml/100 gm/min and intracellular brain pH was 7.01 in both the control and the treated animals. After MCA occlusion, the severely ischemic regions in the control group showed initial and 4-hour postocclusion flows of 12.7 and 5.2 ml/100 gm/min with a brain pH of 6.64 and 6.08, respectively. In animals given nimodipine after MCA occlusion, blood flow increased from 10.5 to 18.8 ml/100 gm/min, with an associated elevation in intracellular brain pH from 6.57 to 6.91. Comparable findings were observed in areas of moderate ischemia. Improvements in cortical blood flow, intracellular brain pH, and EEG attenuations produced by nimodipine were all statistically significant. Inspection of the cortex revealed reversal of cortical pallor and small-vessel spasm following treatment with nimodipine. It is hypothesized that nimodipine exerts its effects through reversal of ischemia-induced secondary vasoconstriction, and that this drug may be an important adjunctive treatment for patients with focal cerebral ischemia.

Thresholds of focal cerebral ischemia in awake monkeys

1981 ◽  
Vol 54 (6) ◽  
pp. 773-782 ◽  
Author(s):  
Thomas H. Jones ◽  
Richard B. Morawetz ◽  
Robert M. Crowell ◽  
Frank W. Marcoux ◽  
Stuart J. FitzGibbon ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cerebral Ischemia ◽  
Middle Cerebral Artery ◽  
Cerebral Artery ◽  
Focal Cerebral Ischemia ◽  
Neurological Function ◽  
Local Flow ◽  
Content Type ◽  
Mca Occlusion ◽  
Fine Print

✓ An awake-primate model has been developed which permits reversible middle cerebral artery (MCA) occlusion during physiological monitoring. This method eliminates the ischemia-modifying effects of anesthesia, and permits correlation of neurological function with cerebral blood flow (CBF) and neuropathology. The model was used to assess the brain's tolerance to focal cerebral ischemia. The MCA was occluded for 15 or 30 minutes, 2 to 3 hours, or permanently. Serial monitoring evaluated neurological function, local CBF (hydrogen clearance), and other physiological parameters (blood pressure, blood gases, and intracranial pressure). After 2 weeks, neuropathological evaluation identified infarcts and their relation to blood flow recording sites. Middle cerebral artery occlusion usually caused substantial decreases in local CBF. Variable reduction in flow correlated directly with the variable severity of deficit. Release of occlusion at up to 3 hours led to clinical improvement. Pathological examination showed microscopic foci of infarction after 15 to 30 minutes of ischemia, moderate to large infarcts after 2 to 3 hours of ischemia, and in most cases large infarcts after permanent MCA occlusion. Local CBF appeared to define thresholds for paralysis and infarction. When local flow dropped below about 23 cc/100 gm/min, reversible paralysis occurred. When local flow fell below 10 to 12 cc/100 gm/min for 2 to 3 hours or below 17 to 18 cc/100 gm/min during permanent occlusion, irreversible local damage was observed. These studies imply that some cases of acute hemiplegia, with blood flow in the paralysis range, might be improved by surgical revascularization. Studies of local CBF might help identify suitable cases for emergency revascularization.

Treatment of experimental focal cerebral ischemia with mannitol

1987 ◽  
Vol 66 (1) ◽  
pp. 109-115 ◽  
Author(s):  
Fredric B. Meyer ◽  
Robert E. Anderson ◽  
Thoralf M. Sundt ◽  
Tony L. Yaksh
Keyword(s):  
Blood Flow ◽  
Focal Cerebral Ischemia ◽  
Gradual Decline ◽  
Vessel Occlusion ◽  
Content Type ◽  
Ph Values ◽  
Brain Ph ◽  
Major Branch ◽  
Severe Ischemia ◽  
Fine Print

✓ Intracellular brain pH, cortical blood flow (CBF), and electrocorticograms were recorded in regions of severe and moderate ischemia in 10 control rabbits and 10 rabbits given mannitol, 1 gm/kg, after occlusion of a major branch of the middle cerebral artery. Pooling the data from all 20 animals, preocclusion CBF was 46.4 ±3.6 ml/100 gm/min and intracellular brain pH was 7.01 ± 0.04 (means ± standard error of the means). Although mannitol administration mildly improved CBF in regions of severe ischemia, this increase was not sufficient to prevent metabolic deterioration as assessed by brain pH. However, in regions of moderate ischemia, CBF improved significantly with mannitol and the gradual decline in brain pH observed in control animals was prevented. For example, in the treated moderate ischemia sites 4-hour postocclusion CBF and pH values were 31.8 ml/100 gm/min and 6.89 ± 0.09, respectively, as compared to control values of 14.3 ml/ 100 gm/min and 6.75 ± 0.06. These results suggest that mannitol may be of benefit in stabilizing regions of moderate, but not severe, ischemia after vessel occlusion.

scholarly journals Nitric Oxide Synthase Inhibition by L-NAME Prevents Brain Acidosis during Focal Cerebral Ischemia in Rabbits

1996 ◽  
Vol 16 (5) ◽  
pp. 988-995 ◽  
Author(s):  
Luca Regli ◽  
Mark C. Held ◽  
Robert E. Anderson ◽  
Fredric B. Meyer
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Cerebral Ischemia ◽  
Focal Cerebral Ischemia ◽  
Dependent Manner ◽  
Cortical Blood Flow ◽  
Nadh Fluorescence ◽  
Brain Ph ◽  
Ischemic Period

This experiment examined the effects of nitric oxide (NO) synthase inhibition on brain intracellular pH, regional cortical blood flow, and NADH fluorescence before and during 3 h of focal cerebral ischemia using in vivo fluorescence imaging. Thirty fasted rabbits under 1% halothane were divided into four treatment groups receiving Nω-nitro-L-arginine methyl ester (L-NAME) intravenously at 20 min prior to ischemia (0.1, I, and 10 mg/kg and 1 mg/kg + 5 mg/kg L-arginine) and two control groups (nonischemic and ischemic). In ischemic controls, brain pHi declined to 6.73 ± 0.03 at 30 min and remained acidotic through the remainder of the ischemic period. In the 0.1 mg/kg group, brain pHi fell after 30 min of ischemia to 6.76 ± 0.05 ( p < 0.05), but then improved progressively despite occlusion. In the 1 mg/kg group, brain pHi remained normal despite middle cerebral artery (MCA) occlusion. In the 10 mg/kg group and in the combined L-NAME + L-arginine group, pHi fell after 30 min of ischemia to 6.81 ± 0.03 ( p < 0.05) and remained acidotic. During occlusion, regional cortical blood flow dropped in a dose-dependent manner. After 3 h of ischemia, regional cortical blood flow was 33.9 ± 10.9 and 25.1 ± 8.9 ml/100 g/min at doses of 0.1 and 10.0 mg/kg, respectively. L-NAME treatment did not significantly alter the increased NADH fluorescence that accompanied occlusion. This study shows that L-NAME can prevent intracellular brain acidosis during focal cerebral ischemia independent from regional cortical blood flow changes. This experiment suggests that NO is involved in pHi regulation during focal cerebral ischemia.

Effect of hyperglycemia on brain pH levels in areas of focal incomplete cerebral ischemia in monkeys

1986 ◽  
Vol 65 (5) ◽  
pp. 693-696 ◽  
Author(s):  
W. Richard Marsh ◽  
Robert E. Anderson ◽  
Thoralf M. Sundt
Keyword(s):  
Adverse Effect ◽  
Cerebral Ischemia ◽  
Cell Damage ◽  
Treated Group ◽  
Squirrel Monkeys ◽  
Control Group ◽  
Content Type ◽  
Brain Ph ◽  
Fine Print ◽  
Incomplete Ischemia

✓ The adverse effect of a minimal cerebral blood flow (CBF) in models of global ischemia has been noted by many investigators. One factor believed important in this situation is the level of blood glucose, since a continued supply of this metabolite results in increased tissue lactate, decreased brain pH, and increased cell damage. The authors have extended these observations to a model of focal incomplete ischemia. Brain pH was measured in fasted squirrel monkeys in regions of focal incomplete ischemia after transorbital occlusion of the middle cerebral artery (MCA). In both control and hyperglycemic animals, CBF was reduced to less than 30% of baseline. At 3 hours after MCA occlusion, brain pH in the control group was 6.66 ± 0.68 as compared to 6.27 ± 0.26 in the glucose-treated group. This difference was statistically significant by Student's unpaired t-test (p < 0.05). Thus, hyperglycemia results in decreased tissue pH in regions of focal incomplete cerebral ischemia in monkeys.

Nonhyperemic blood flow restoration and brain edema in experimental focal cerebral ischemia

1989 ◽  
Vol 70 (1) ◽  
pp. 73-80 ◽  
Author(s):  
Toshihiko Kuroiwa ◽  
Makoto Shibutani ◽  
Riki Okeda
Keyword(s):  
Blood Flow ◽  
Cerebral Ischemia ◽  
Brain Edema ◽  
Focal Cerebral Ischemia ◽  
Reactive Hyperemia ◽  
Diffusion Method ◽  
Left Middle Cerebral Artery ◽  
Content Type ◽  
Bbb Opening ◽  
Fine Print

✓ The effect of suppression of postischemic reactive hyperemia on the blood-brain barrier (BBB) and ischemic brain edema after temporary focal cerebral ischemia was studied in cats under ketamine and alpha-chloralose anesthesia. Regional cerebral blood flow (rCBF) was measured by a thermal diffusion method and a hydrogen clearance method. The animals were separated into three groups. In Group A, the left middle cerebral artery (MCA) was occluded for 6 hours. In Group B, the MCA was occluded for 3 hours and then reperfused for 3 hours; postischemic hyperemia was suppressed to the preischemic level by regulating the degree of MCA constriction. In Group C, the MCA was occluded for 3 hours and reperfused for 3 hours without suppressing the postischemic reactive hyperemia. The brain was removed and cut coronally at the site of rCBF measurement. The degree of ischemic edema was assessed by gravimetry in samples taken from the coronal section and correlated with the degree of BBB disruption at the corresponding sites, evaluated by densitometric determination of Evans blue discoloration. The findings showed that 1) ischemic edema was significantly exacerbated by postischemic hyperemia during reperfusion in parallel with the degree of BBB opening to serum proteins, and 2) suppression of postischemic hyperemia significantly reduced the exacerbation of ischemic edema and BBB opening. These findings indicate that blood flow may be restored without significant exacerbation of postischemic edema by the suppression of postischemic hyperemia in focal cerebral ischemia.

Decompressive craniectomy in a rat model of “malignant” cerebral hemispheric stroke: experimental support for an aggressive therapeutic approach

1996 ◽  
Vol 85 (5) ◽  
pp. 853-859 ◽  
Author(s):  
Arnd Doerfler ◽  
Michael Forsting ◽  
Wolfgang Reith ◽  
Christian Staff ◽  
Sabine Heiland ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Decompressive Craniectomy ◽  
Control Group ◽  
Acute Ischemia ◽  
Vessel Occlusion ◽  
Content Type ◽  
Time Points ◽  
Infarction Size ◽  
Mca Occlusion ◽  
Fine Print

✓ Acute ischemia in the complete territory of the carotid artery may lead to massive cerebral edema with raised intracranial pressure and progression to coma and death due to uncal, cingulate, or tonsillar herniation. Although clinical data suggest that patients benefit from undergoing decompressive surgery for acute ischemia, little data about the effect of this procedure on experimental ischemia are available. In this article the authors present results of an experimental study on the effects of decompressive craniectomy performed at various time points after endovascular middle cerebral artery (MCA) occlusion in rats. Focal cerebral ischemia was induced in 68 rats using an endovascular occlusion technique focused on the MCA. Decompressive cranioectomy was performed in 48 animals (in groups of 12 rats each) 4, 12, 24, or 36 hours after vessel occlusion. Twenty animals (control group) were not treated by decompressive craniectomy. The authors used the infarct volume and neurological performance at Day 7 as study endpoints. Although the mortality rate in the untreated group was 35%, none of the animals treated by decompressive craniectomy died (mortality 0%). Neurological behavior was significantly better in all animals treated by decompressive craniectomy, regardless of whether they were treated early or late. Neurological behavior and infarction size were significantly better in animals treated very early by decompressive craniectomy (4 hours) after endovascular MCA occlusion (p < 0.01); surgery performed at later time points did not significantly reduce infarction size. The results suggest that use of decompressive craniectomy in treating cerebral ischemia reduces mortality and significantly improves outcome. If performed early after vessel occlusion, it also significantly reduces infarction size. By performing decompressive craniectomy neurosurgeons will play a major role in the management of stroke patients.

Microregional blood flow changes in experimental cerebral ischemia

1971 ◽  
Vol 35 (2) ◽  
pp. 155-166 ◽  
Author(s):  
Y. Lucas Yamamoto ◽  
Kathryne M. Phillips ◽  
Charles P. Hodge ◽  
William Feindel
Keyword(s):  
Blood Flow ◽  
Cerebral Ischemia ◽  
Fluorescein Angiography ◽  
Focal Cerebral Ischemia ◽  
Gamma Activity ◽  
Collateral Flow ◽  
Silicon Detectors ◽  
Content Type ◽  
Perfusion Flow ◽  
The Brain

✓ A branch of the middle cerebral artery on the convexity of the dog brain was occluded to produce an area of focal cerebral ischemia which could then be defined by fluorescein angiography of the brain. Repeated fluorescein angiography and measurement of microregional cerebral blood flow by xenon133 injected into the carotid artery and monitored by miniature lithium-drifted silicon detectors for gamma activity demonstrated that the ischemic zone was reduced in size by better collateral flow when the animals were allowed to breathe 5% carbon dioxide and 95% oxygen. Conversely, hyperventilation reducing the pCO2 made the ischemic zone larger by reducing collateral flow. No evidence was found to indicate that hypercapnia preferentially deprived the ischemic zone of perfusion flow. Retrograde collateral flow in the surface arteries appeared effective in terms of microcirculatory perfusion.

Impaired microvascular filling after focal cerebral ischemia in monkeys

1972 ◽  
Vol 36 (3) ◽  
pp. 303-309 ◽  
Author(s):  
Robert M. Crowell ◽  
Yngve Olsson
Keyword(s):  
Cerebral Ischemia ◽  
Focal Cerebral Ischemia ◽  
Cerebrovascular Diseases ◽  
Subcortical Structures ◽  
Content Type ◽  
Microsurgical Technique ◽  
Small Vessels ◽  
Mca Occlusion ◽  
Vascular Channels ◽  
Fine Print

✓ Impairment of microvascular filling was demonstrated in relation to focal cerebral ischemia in the monkey. Temporary or sustained middle cerebral artery (MCA) clipping was achieved with a microsurgical technique. Animals were sacrificed by perfusion with a carbon black suspension. Brains were fixed in formalin, and the extent of microvascular carbon filling was estimated grossly and microscopically. In most animals, MCA occlusion of 2 hours to 7 days produced diminished filling in small vessels in the MCA territory of supply. The impairment of filling was most pronounced in the deep subcortical structures but also affected the cortex in some animals. Temporary and sustained occlusion of equal duration produced roughly equivalent areas of abnormal filling. The impairment of vascular filling tended to be more extensive with increasing duration of occlusion. Hypotension during MCA occlusion caused almost total non-filling of the microvasculature in the entire MCA territory. Impaired filling of vascular channels may play a role in the pathogenesis of some clinical cerebrovascular diseases.

scholarly journals The Novel Dihydronaphthyridine Ca2+ Channel Blocker CI-951 Improves CBF, Brain pHi, and EEG Recovery in Focal Cerebral Ischemia

1990 ◽  
Vol 10 (1) ◽  
pp. 97-103 ◽  
Author(s):  
Fredric B. Meyer ◽  
Robert E. Anderson ◽  
Thoralf M. Sundt
Keyword(s):  
Cerebral Ischemia ◽  
Therapeutic Agent ◽  
Channel Blocker ◽  
Focal Cerebral Ischemia ◽  
The Novel ◽  
Halothane Anesthesia ◽  
Mca Occlusion ◽  
Brain Ph ◽  
To Receive

The effects of the novel dihydronaphthyridine Ca2+ antagonist CI-951 on focal cerebral ischemia were assessed during MCA occlusion in 30 white New Zealand rabbits under 1.0% halothane anesthesia. In vivo brain pHi and focal CBF were measured with umbelliferone fluorescense. Baseline normocapnic brain pHi and CBF were 7.02 ± 0.02 and 48.4 ± 2.9 ml/100 g/min, respectively. In the severe ischemic regions, 15 min postocclusion brain pHi, and CBF were 6.62 ± 0.04 and 14.4 ± 0.7 ml/100 g/min in controls vs. 6.60 ± 0.02 and 12.9 ± 2.3 ml/100 g/min, respectively, in animals destined to receive CI-951. Twenty minutes after MCA occlusion, CI-951 was administered at 0.5 μg/kg/min and brain pHi and CBF were determined in both regions of severe and moderate ischemia for 4 h postocclusion. Control severe ischemic sites demonstrated no significant improvement in brain pHi and only mild increases in CBF over the next 4 h. CI-951 caused significant improvement in both of these parameters. Postocclusion 4 h brain pHi and CBF measured 6.69 ± 0.04 and 18.5 ± 3.2 ml/100 g/min in controls vs. 7.01 ± 0.04 and 41.7 ± 5.3 ml/100 g/min, respectively, in CI-951 animals ( p < 0.001). Similar improvements were observed in moderate ischemic sites. In animals that demonstrated postocclusion EEG attenuation, 75% of CI-951 animals had EEG recovery as compared to 18% in controls. CI-951 may be a useful therapeutic agent for focal cerebral ischemia if histological and outcome studies verify these data.

Spinal cord stimulation reducing infarct volume in a model of focal cerebral ischemia in rats

2003 ◽  
Vol 99 (1) ◽  
pp. 131-137 ◽  
Author(s):  
Oren Sagher ◽  
Dah-Luen Huang ◽  
Richard F. Keep
Keyword(s):  
Spinal Cord ◽  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Cerebral Ischemia ◽  
Spinal Cord Stimulation ◽  
Focal Cerebral Ischemia ◽  
Doppler Flowmetry ◽  
Content Type ◽  
Baseline Values ◽  
Fine Print

Object. The authors previously showed that spinal cord stimulation (SCS) increases cerebral blood flow in rats, indicating that this technique may be useful in the treatment of focal cerebral ischemia. In the present study, the neuroprotective potential of SCS in the setting of middle cerebral artery occlusion (MCAO) was investigated. Methods. The authors induced permanent, focal cerebral ischemia by using either suture-induced occlusion or direct division of the MCA in Sprague—Dawley rats. Electrical stimulation of the cervical spinal cord was performed during cerebral ischemia. Cerebral blood flow was assessed using both laser Doppler flowmetry (LDF) and quantitative radiotracer analysis. Stroke volumes were analyzed after 6 hours of ischemia. Spinal cord stimulation resulted in a 52.7 ± 13.3% increase in LDF values (nine animals). Following MCAO, LDF values decreased by 64.1 ± 3.6% from baseline values (10 animals). Spinal cord stimulation subsequently increased LDF values to 30.9 ± 13.5% below original baseline values. These findings were corroborated using radiotracer studies. Spinal cord stimulation in the setting of transcranial MCAO significantly reduced stroke volumes as well (from 203 ± 33 mm3 [control] to 32 ± 8 mm3 [MCAO plus SCS], seven animals in each group, p < 0.001). Similarly, after suture-induced MCAO, SCS reduced stroke volumes (from 307 ± 29 mm3 [control] to 78 ± 22 mm3 [MCAO plus SCS], 10 animals in each group, p < 0.001). Conclusions. A strategy of performing SCS for the prevention of critical ischemia is feasible and may have the potential for the treatment and prevention of stroke.

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