Glutamate release from the ovine fetal brain during maternal hemorrhage. A study using chronic in utero cerebral microdialysis.
BACKGROUND
Glutamate has been implicated in the pathophysiology of neuronal injury associated with cerebral hypoxia-ischemia. A model using chronic in utero microdialysis was developed to sample the extracellular space of the fetal brain. Using this model, we tested the hypothesis that glutamate efflux from the parasagittal parietal cortex of near-term fetuses would increase during maternal hemorrhage.


METHODS
Twelve near-term fetal sheep were instrumented with vascular catheters, and a microdialysis probe(s) was implanted into the parasagittal parietal cortex. After a 3-day recovery period, the animals were subjected to maternal hemorrhage until either the fetal pH was < 7.00 or the fetus died. The extracellular glutamate concentration in the collected dialysate was determined by high pressure liquid chromatography (HPLC).


RESULTS
Maternal hemorrhage resulted in an 80-90% decrease in uterine blood flow, a decrease fetal po2, and a mixed metabolic and respiratory fetal acidosis. There were two groups of fetuses, survivors (n = 5) and nonsurvivors (n = 7). The nonsurvivor group showed a large increase (10-30-fold) in peak glutamate release (P = 0.0015). Survivors demonstrated a small (threefold) increase that was not statistically significant (P = 0.065), unless one animal with very low probe recovery was excluded (P = 0.0048).


CONCLUSIONS
Extracellular glutamate release from the fetal brain can occur during maternal hemorrhage with fetal acidemia. The pathophysiologic role (if any) of glutamate release in the survivors remains to be elucidated. Our results are consistent with the hypothesis that in utero release of glutamate occurs during periods of fetal asphyxia. This experimental preparation of chronic fetal brain microdialysis can be used to monitor the brain extracellular concentration of any dialyzable substance in response to stress, including maternal hemorrhage.
Department of Anesthesia, University of Iowa College of Medicine, Iowa City 52242-1079.
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Penning
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Chestnut
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Dexter
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Hrdy
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Poduska
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Atkins
D000818:Animals; D016063:Blood Loss, Surgical; D001921:Brain / Q000196:embryology*; D005260:Female; D005313:Fetal Death; D005971:Glutamates / Q000378:metabolism*; D006439:Hemodynamics; D006863:Hydrogen-Ion Concentration; D000860:Hypoxia / Q000378:metabolism*; D017551:Microdialysis; D011247:Pregnancy; D012756:Sheep
D005971:Glutamates