This study investigated the influence of temperature or
glutamate antagonism on the immediate outcome of perinatal
asphyxia. Perinatal
asphyxia was produced by water immersion of fetus-containing uterus horns removed by
cesarean section from ready to deliver rats. The uterus horns were kept in a water bath for different time periods, before the pups were delivered and stimulated to breathe. After delivery, the pups were assessed for behavior and for systemic
glutamate,
aspartate,
lactate and
pyruvate levels measured with in vivo microdialysis, or ex vivo for energy-rich
phosphates, including
adenosine triphosphate (
ATP), in brain, heart and kidney. In a series of experiments,
asphyxia was initiated in a water bath at 37 degrees C, before the pup-containing uterus horns were moved for different time intervals to a 15 degrees C bath. In another series of experiments, the mothers were treated with
N-methyl-D-aspartate (
NMDA) antagonist,
dizocilpine (MK-801), or alpha-amino-3-hydroxy-methylisoxazole-4-propionic
acid (
AMPA) antagonist,2,3-dihydroxy-6-nitro-7-sulfamoyl benzo(f) quinoxalin
NBQX) 1 h before
hysterectomy and
asphyxia at 37 degrees C. The rate of survival rapidly decreased following exposure to more than 16 min of
asphyxia, and no survival could be observed after 22 min of
asphyxia. An LD50 was estimated to occur at approximately 19 min of
asphyxia. The outcome was paralleled by a decrease in
ATP in kidney, followed by a decrease in heart and brain. A maximal decrease in
ATP was observed after 20 min of
asphyxia in all tissues. Systemic microdialysis revealed that
glutamate,
aspartate and
pyruvate levels were increased with a peak after 5 min of
asphyxia. In contrast,
lactate levels increased along with the length of the insult. Survival was increased when the pup-containing uterus horns were moved from a 37 degrees C to a 15 degrees C bath, at 15 min of
asphyxia (the LD50 was thus increased to 30 min). If the shift occurred
at 10 or 5 min of
asphyxia, the LD50 increased to 80 or 110 min, respectively. The effect of
glutamate antagonism was minor compared to
hypothermia; the best effect (an increase in the LD50 to approximately 22 min) was observed after combining
AMPA and
NMDA antagonists.