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 glyco lytic rates and brain lactate accumulation after complete ischemia ind uced by cardiac arrest. Before cardiac arrest, the blood plasma glucos e concentration in seven newborn (113 d postconception; normal gestati on, 115 d) and seven 1-mo-old (144 d postconception) piglets was adjus ted to a specific value (range, 1 to 64 mM), and then inspired ventila tion gases were changed to 10:50:40 CO2:O2:N2 for 20 min. The agonal g lycolytic rate was measured by monitoring the rate of cerebral lactate formation in vivo using proton nuclear magnetic resonance spectroscop y, and postmortem brain lactate concentrations were measured biochemic ally in tissue extracts obtained 40 to 45 min after cardiac arrest. Th ese data were compared with 21 normocarbic piglets of similar age, nin e examined as part of the present study and 12 examined previously (Co rbett RJT, Laptook AR, Ruley JI, Garcia D: Pediatr Res 30:579-586, 199 1). There was a nonlinear relationship between the final postmortem br ain lactate concentration and preischemia blood plasma glucose concent ration that was most prominent in newborn piglets and previously had g one unnoticed. When analyzed using a steady-state model for glucose tr ansport, this relationship revealed that normocarbic newborns had a lo wer preischemia affinity constant for the transport mechanism for gluc ose (2.8 +/- 1.5 mM) and lower cerebral glucose utilization rate relat ive 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 hypercar bia, these differences diminish, suggesting that newborn and 1-mo-olds had nearly identical affinity constants of transport mechanism for gl ucose (3.7 +/- 0.8 and 4.0 +/- 0.4 mM, respectively) and identical cer ebral glucose utilization rate relative to transport rate (0.21 +/- 0. 03 and 0.23 +/- 0.01, respectively). For 1-mo-olds, hypercarbia substa ntially 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 conc entration of plasma glucose (6.86 +/- 3.00 to 1.27 +/- 0.41 mM) at whi ch the half maximal rate of utilization occurs, whereas in newborns th e 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 decr eases agonal glycolytic rate in 1-mo-olds.