Cerebral Metabolism during Cord Occlusion and Hypoxia in the Fetal Sheep: A Novel Method of Continuous Measurement Based on Heat Production

Abstract

This study was undertaken to validate a new method of measuring cerebral metabolic rate in the fetal sheep based on heat production in a local region of the brain. Heat production was compared to oxygen use in 20 near-term fetuses during basal conditions, moderate hypoxia and cord occlusion. Thermocouples were placed to measure core and brain temperature and a composite probe placed in the parietal cortex to measure changes in cortical blood flow (CBF) using laser Doppler flowmetry and tissue PO2 using fluorescent decay. Catheters were inserted in a brachiocephalic artery and sagittal sinus for blood sampling. With moderate hypoxia, induced by administering 10-12 % oxygen to the ewes, fetal arterial PO2 declined from 23 +/- 1 to 11 +/- 1 Torr and brain tissue PO2 fell from 7.6+/- 0.7 to a nadir of 0.8 +/- 0.4 Torr, while CBF increased to 139 +/- 5 % of baseline. Cortical heat production, calculated as the product of CBF, the temperature gain from artery to brain tissue, and the specific heat of blood, decreased by 45 +/- 11 % in parallel to similar declines in oxygen uptake. With severe asphyxia induced by complete cord occlusion for 10 min, fetal arterial PO2 declined from 23 +/- 1 to 9 +/- 2 Torr and brain tissue PO2 fell from 7.0 +/- 0.7 to essentially 0 Torr while CBF decreased 40 +/- 5 %. Cortical heat production decreased by 78 +/- 6 % while oxygen use declined by 90 +/- 3 %. Glucose uptake increased significantly relative to oxygen use and lactate concentration increased in sagittal sinus blood. We conclude that local measurements of heat production in the brain provide a useful index of overall metabolic rate, closely reflecting oxygen use in moderate hypoxia and indicating a significant contribution from anaerobic metabolism during severe asphyxia.