Previous studies have shown that hypoxia results in modification of the N-methyl-D-aspartate (NMDA) receptor/ion channel complex and a decrease in the concentrations of high energy phosphate compounds in the cerebral cortices of newborn piglets. The present study investigates the effect of reoxygenation with either 21% or 100% oxygen following hypercapnic hypoxia on the glutamate site of the NMDA receptor. 6 anesthetized and ventilated newborn piglets were exposed to 60-80 minutes of hypercapnic hypoxia followed by a 45 minute period of reoxygenation in 21% (n=3) or 100% (n=3) oxygen. Hypercapnic hypoxia was achieved by the slow addition of CO2 to the inhalational gases followed by a reduction in the FiO2 to 0.05-0.07. Prior to reoxygenation, values for pH, PaCO2 and PaO2 (mean ± SD) in the 21% and 100% groups were: 7.07±0.02 vs. 7.04±0.01, 84±3 vs. 80±5 mmHg and 20±2 vs. 21±0 mmHg, respectively. After the period of reoxygenation, brain tissue was removed for analysis. Concentrations in the 21% and 100% groups for ATP (mean±SD): 5.28±0.22 vs. 4.60±0.21 μmoles/g, and phosphocreatine: 3.64±0.08 vs. 3.11±0.09 μmoles/g, respectively, were similar to normoxic controls.3 H-glutamate binding assays were performed in a concentration range from 25 to 1000 nM. The numbers of NMDA-specific glutamate sites (Bmax) in the 21% and 100% groups were 737±213 and 607±86 fmol/mg protein(mean±SD), and Kd values were 406±192 and 301±128 nM, respectively. While there are no differences in the concentrations of high energy phosphate compounds or 3H-glutamate binding between the two groups immediately after reoxygenation, we speculate that delayed neuronal injury may still occur since in previous studies we have demonstrated more free radical production following post-hypoxic reoxygenation with 100% oxygen.

(Funded by AAP/AHA/Neonatal Resuscitation Program; NIH# HD-20337).