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  • By Author: Meyer, Fredric B. x
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Treatment of experimental focal cerebral ischemia with mannitol

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

Fredric B. Meyer, Robert E. Anderson, Thoralf M. Sundt Jr. and Tony L. Yaksh

✓ 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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Fredric B. Meyer, Robert E. Anderson, Tony L. Yaksh and Thoralf M. Sundt Jr.

✓ 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.