Comparison between hypothermia and glutamate antagonism treatments on the immediate outcome of perinatal asphyxia

This study investigated the influence of temperature or glutamate antagonis m on the immediate outcome of perinatal asphyxia. Perinatal asphyxia was pr oduced by water immersion of fetus-containing uterus horns removed by cesar ean section from ready to deliver rats. The uterus horns were kept in a wat er bath for different time periods, before the pups were delivered and stim ulated to breathe. After delivery, the pups were assessed for behavior and for systemic glutamate, aspartate, lactate and pyruvate levels measured wit h in vivo microdialysis, or ex vivo for energy-rich phosphates, including a denosine triphosphate (ATP), in brain, heart and kidney. In a series of exp eriments, asphyxia was initiated in a water bath at 37 degreesC, before the pup-containing uterus horns were moved for different time intervals to a 1 5 degreesC bath. In another series of experiments, the mothers were treated with N-methyl-D-aspartate (NMDA) antagonist, dizocilpine (MK-801), or alph a -amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) antagonist, 2, 3-dihydroxy-6-nitro-7-sulfamoyl benzo(f) quinoxaline (NBQX) 1 h before hyst erectomy and asphyxia at 37 degreesC. The rate of survival rapidly decrease d 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 si milar to 19 min of asphyxia. The outcome was paralleled by a decrease in AT P 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 micro dialysis revealed that glutamate, aspartate and pyruvate levels were increa sed with a peak after 5 min of asphyxia. In contrast, lactate levels increa sed along with the length of the insult. Survival was increased when the pu p-containing uterus horns were moved from a 37 degreesC to a 15 degreesC ba th, at 15 min of asphyxia (the LD50 was thus increased to 30 min). If the s hift occurred at 10 or 5 min of asphyxia, the LD50 increased to 80 or 110 m in, respectively. The effect of glutamate antagonism was minor compared to hypothermia; the best effect (an increase in the LD50 to similar to 22 min) was observed after combining AMPA and NMDA antagonists.