CEREBRAL LACTATE METABOLISM IN NEAR-TERM FETAL SHEEP

The present study was designed to see if lactate can cross the blood-brain barrier of the near-term fetal sheep and replace glucose as an oxidative substrate during normoglycemia and acute insulin-induced hypoglycemia. Cerebral uptake of glucose, oxygen, lactate, and [C-14]lactate as well as cerebral production of (CO2)-C-14 were measured under three conditions: 1) normoglycemia-normolactemia, 2) acute hypoglycemia-normolactemia, and 3) hypoglycemia-steady-state hyperlactemia. Although uptake of tracer [C-14]lactate was consistent, there was no net uptake of unlabeled lactate during either normoglycemia or hypoglycemia. When arterial lactate concentration was raised from 2.2 +/- 0.5 to 3.3 +/- 0.4 (SE) mM by sodium lactate infusion, however, lactate was taken up. Comparison of cerebral [C-14]lactate uptake with (CO2)-C-14 production indicated that the principal metabolic fate of lactate is oxidation. At increased concentrations, exogenous lactate accounted for similar to 7% of cerebral oxygen consumption. This study demonstrates that lactate crosses the blood-brain barrier of the near-term fetal sheep, is oxidized, and at elevated concentrations can partially replace glucose as an oxidative substrate during acute hypoglycemia.