THE EFFECT OF HYPERCARBIA ON AGE-RELATED-CHANGES IN CEREBRAL GLUCOSE-TRANSPORT AND GLUCOSE-MODULATED AGONAL GLYCOLYTIC RATES

This study examined the effect of hypercarbia on cerebral agonal glycolytic rates and brain lactate accumulation after complete ischemia induced by cardiac arrest. Before cardiac arrest, the blood plasma glucose concentration in seven newborn (113 d postconception; normal gestation, 115 d) and seven 1-mo-old (144 d postconception) piglets was adjusted to a specific value (range, 1 to 64 mM), and then inspired ventilation gases were changed to 10:50:40 CO2:O2:N2 for 20 min. The agonal glycolytic rate was measured by monitoring the rate of cerebral lactate formation in vivo using proton nuclear magnetic resonance spectroscopy, and postmortem brain lactate concentrations were measured biochemically in tissue extracts obtained 40 to 45 min after cardiac arrest. These data were compared with 21 normocarbic piglets of similar age, nine examined as part of the present study and 12 examined previously (Corbett RJT, Laptook AR, Ruley JI, Garcia D: Pediatr Res 30:579-586, 1991). There was a nonlinear relationship between the final postmortem brain lactate concentration and preischemia blood plasma glucose concentration that was most prominent in newborn piglets and previously had gone unnoticed. When analyzed using a steady-state model for glucose transport, this relationship revealed that normocarbic newborns had a lower preischemia affinity constant for the transport mechanism for glucose (2.8 +/- 1.5 mM) and lower cerebral glucose utilization rate relative to transport rate (0.12 +/- 0.04), compared with 1-mo-olds (4.5 +/- 1.4 mM and 0.30 +/- 0.03, respectively). In the presence of hypercarbia, these differences diminish, suggesting that newborn and 1-mo-olds had nearly identical affinity constants of transport mechanism for glucose (3.7 +/- 0.8 and 4.0 +/- 0.4 mM, respectively) and identical cerebral glucose utilization rate relative to transport rate (0.21 +/- 0.03 and 0.23 +/- 0.01, respectively). For 1-mo-olds, hypercarbia substantially decreased the maximal rate of agonal glucose utilization (3.93 +/- 0.55 to 1.75 +/- 0.11 mumol . g-1 . min-1) and decreased the concentration of plasma glucose (6.86 +/- 3.00 to 1.27 +/- 0.41 mM) at which the half maximal rate of utilization occurs, whereas in newborns the relative decrease produced by hypercarbia was not as prominent (1.46 +/- 0.14 to 1.12 +/-0.22 mumol.g-1.min-1 and 0.93 +/- 0.66 to 0.80 +/- 1.14 mM, respectively). To the extent that lactic-acidosis enhances irreversible tissue damage, hypercarbia could be beneficial for either age group because hypercarbia reduces both agonal glycolytic rate and brain tissue glucose concentration in newborns and substantially decreases agonal glycolytic rate in 1-mo-olds.