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Evaluation of hemodilution and hypothermia in a rat model of global cerebral ischemia



Evaluation of hemodilution and hypothermia in a rat model of global cerebral ischemia



Proceedings of the Oklahoma Academy of Science 80: 7-16



Cerebrovascular disease and trauma are major causes of death and disability in the United States. Studies have shown that hypothermia can reduce neuronal damage and improve recovery from cerebral ischemia or trauma in animal models, but the optimal use of hypothermia in combination with other treatment modalities has not been established. We studied the combined effect of hemodilution and hypothermia in a rat model of global cerebral ischemia based on the hypothesis that hypothermia may reduce neuronal oxygen requirements, whereas hemodilution may increase cerebral blood flow. Hemodilution was accomplished by intravenous injection of saline. Rats were randomly assigned to three experimental groups: normothermic with a sham injection (sham control), normothermic with a saline injection (normothermic), and hypothermic with a saline injection (hypothermic). Cerebral ischemia was produced by cauterization of the vertebral arteries followed by ligation of the carotid arteries for 10 min. Body and cerebral temperature, cerebral blood flow, and electroencephalographic activity were monitored during ischemia and a 2-h post-ischemic treatment. Cerebral ischemia was followed by a 15-min period of reactive hyperemia, and then a sustained period of hypoperfusion in all treatment groups. Mortality in the hypothermic group (0%) was significantly less than in sham animals (32%). The total number of viable hippocampal CA 1 neurons 21 d after ischemia was greater in the normothermic and hypothermic rats than in the sham group, but the differences were not significant. Motor function improved in all treatment groups between 7 and 21 d post-ischemia. The foot-fault test failed to show significant differences between groups at any time, though there was a trend toward a lower foot-fault rate in hypothermic animals at 7 d. Hypothermia significantly decreased mortality, but this improvement was not reflected by the total number of viable hippocampal neurons or by a motor function test.

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