EVALUATION OF POTENTIAL EFFECTORS OF AGONAL GLYCOLYTIC RATE IN DEVELOPING BRAIN MEASURED IN-VIVO BY P-31 AND H-1 NUCLEAR-MAGNETIC-RESONANCESPECTROSCOPY

Previously we have shown that hypercarbia produces a larger decrease i n agonal glycolytic rate in 1-month-old swine than in newborns. In an effort to understand the mechanism responsible for this difference, we tested the hypothesis that hypercarbia produces age-related changes i n the concentration of one or more effecters of phosphofructokinase ac tivity. Specifically, in vivo P-31 and H-1 NMR spectroscopy was used t o compare changes in lactate levels, intracellular pH, free magnesium concentration, and content of phosphorylated metabolites for these two age groups at three intervals during the first 1.5 min of complete is chemia in the presence or absence of hypercarbia (PaCO2 = 102-106 mm H g). Hypercarbia produced the same drop in intracellular brain pH for b oth age groups, but the decrease in phosphocreatine level and increase in inorganic phosphate content were greater in I-month-olds compared with newborns. During ischemia there was no difference between the mag nitude of change in intracellular pH and levels of phosphocreatine and inorganic phosphate in hypercarbic I-month-olds versus newborns. Unde r control conditions, i.e., normocarbia and normoxia, the free Mg2+ co ncentration was lower and the fraction of magnesium-free ATP was highe r for newborns than I-month-olds. However, there was no change in thes e variables for either age group during hypercarbia and early during i schemia. Thus, age-related differences in the relative decrease in ago nal glycolytic rate during hypercarbia could not be explained by diffe rences in intracellular pH, inorganic phosphate content, or free magne sium concentration. The [ADP](free) at control was higher in newborns compared with I-month-olds, and there was no age-related difference in [AMP](free). These variables did not change for newborns when exposed to hypercarbia, but for 1-month-olds [ADP](free) and [AMP](free) incr eased during hypercarbia relative to control values. High-energy phosp hate utilization during ischemia for hypercarbic 1-month-olds was redu ced by 74% compared with normocarbic I-month-olds during ischemia, whe reas the reduction in energy utilization (14%) was not significant for hypercarbic versus normocarbic newborns during ischemia. Because hype rcarbia reduces the rate of ATP depletion during ischemia in I-month-o lds to a greater extent than in newborns, the increase in [ADP](free) and [AMP](free) will be slower in the former age group. It follows the refore that for 1-month-olds, the agonal glycolytic rate would not be accelerated by ADP and AMP to the same degree during hypercarbia plus ischemia compared with normocarbic plus ischemia, whereas for newborns hypercarbia has relatively little impact on agonal glycolytic rate.