THE EFFECT OF AGE ON GLUCOSE-MODULATED CEREBRAL AGONAL GLYCOLYTIC RATES MEASURED INVIVO BY H-1-NMR SPECTROSCOPY

The purpose of this study was to investigate the effect of plasma glucose concentration on cerebral agonal glycolytic rates in piglets of different ages. Twenty-four piglets were divided into four different age groups corresponding to 113, 121, 128, and 145 d postconception (normal gestation = 115 d). For each group the agonal glycolytic rate was measured by monitoring the rate of cerebral lactate accumulation after total ischemia. Ischemia was induced by cardiac arrest, and the rate of lactate formation was measured in vivo using proton nuclear magnetic resonance spectroscopy. Before cardiac arrest, the blood plasma glucose concentration for individual piglets was adjusted to a specific value in the range 1-30 mM. The dependence of agonal glycolytic rate upon blood glucose concentration was analyzed for each age group, using the Michaelis-Menten equation to evaluate V(max), the maximal rate of glucose utilization, and Km the concentration of plasma glucose at which the half maximal rate of utilization occurs. V(max) for the two youngest age groups of piglets had significantly different (p < 0.05) values compared with each other (1.38 +/- 0.17 and 1.92 +/- 0.64-mu-mol.g-1.min-1, respectively) and with the two older groups of animals (2.99 +/- 0.52 and 3.42 +/- 0.65-mu-mol.g-1.min-1, respectively). The Km values determined for the two youngest age groups (0.79 +/- 0.70 and 1.79 +/- 0.33 mM, respectively) also were significantly lower than for the two older age groups (4.96 +/- 2.90 and 4.82 +/- 2.96 mM, respectively). We conclude that throughout the first 2 wk of life there are marked increases in the cerebral glycolytic capacity. It follows, therefore, that rates of lactate formation in newborns are not as strongly accelerated by increased blood glucose compared with older piglets. During combined hyperglycemia and severe ischemia, newborns will not be exposed to harmful levels of cerebral lactate as rapidly as 2- to 4-wk-old piglets. However, despite the differences in glycolytic rates, all four age groups showed similar potentials to generate high cerebral lactate concentrations. Furthermore, the final brain lactate concentration showed the same linear correlation with preischemia plasma glucose concentration for all four age groups. The implications of this study are that piglets of any age have the same potential to generate high concentrations of brain lactate, although newborns will reach this level more slowly than older animals.