EVALUATION OF POTENTIAL EFFECTORS OF AGONAL GLYCOLYTIC RATE IN DEVELOPING BRAIN MEASURED IN-VIVO BY P-31 AND H-1 NUCLEAR-MAGNETIC-RESONANCESPECTROSCOPY
Rjt. Corbett et al., EVALUATION OF POTENTIAL EFFECTORS OF AGONAL GLYCOLYTIC RATE IN DEVELOPING BRAIN MEASURED IN-VIVO BY P-31 AND H-1 NUCLEAR-MAGNETIC-RESONANCESPECTROSCOPY, Journal of neurochemistry, 64(1), 1995, pp. 322-331
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.