Treatment of experimental focal cerebral ischemia with mannitol

Assessment by intracellular brain pH, cortical blood flow, and electroencephalography

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✓ 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.

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Address reprint requests to: Fredric B. Meyer, M.D., Department of Neurosurgery, Mayo Clinic, Rochester, Minnesota 55905.

© AANS, except where prohibited by US copyright law.

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    Graph of intracellular brain pH and cortical blood flow (CBF) in severely ischemic sites in 10 control animals (solid lines) and severely ischemic sites in 10 animals treated with an intravenous (IV) bolus of mannitol (dashed lines). Pooling data from all 20 animals, CBF obtained before middle cerebral artery (MCA) occlusion was 46.4 ± 3.6 ml/100 gm/min and intracellular brain pH was 7.01 ± 0.04. Immediately postocclusion, CBF was 12.0 ± 2.5 ml/100 gm/min in the control group and 13.2 ± 1.6 ml/100 gm/min in the treated group, and brain pH was 6.65 ± 0.05 in the control group and 6.58 ± 0.05 in the treated group. The control group demonstrated a progressive decline in CBF and brain pH over the ensuing 4 hours. Although mannitol treatment stabilized CBF, this improvement was not sufficient to significantly alter intracellular brain pH. Three animals without MCA occlusion (dotted lines) served as time controls,

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    Graph of intracellular brain pH and cortical blood flow (CBF) in moderately ischemic sites in 10 control animals (solid lines) and moderately ischemic sites in 10 animals treated with an intravenous (IV) bolus of mannitol (dashed lines). After occlusion of the middle cerebral artery (MCA), CBF was 21.0 ± 2.0 ml/100 gm/min in the control group and 23.8 ± 1.0 ml/100 gm/min in the treated group while brain pH was 6.95 ± 0.05 and 6.85 ± 0.04, respectively. With infusion of mannitol, there was a progressive improvement in CBF: flow at the 4th hour postocclusion was 31.8 ± 5.2 ml/100 gm/min as compared to 14.3 ± 3.5 ml/100 gm/min in the control group (p < 0.001). This resulted in gradual improvement in intracellular brain pH as opposed to the gradual decline observed in controls: at the 4th hour postocclusion, brain pH was 6.89 ± 0.09 in the treated group as compared to 6.75 ± 0.06 in the control group (p < 0.01). Three animals without MCA occlusion (dotted lines) served as time controls.

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