Impaired energy metabolism in the brains of newborn infants with increased cerebral echodensities

on the intact dura, in order to determine intracellular pH (pH,) and the relative concentrations of phosphorus energy metabolites. In three animals, brain lactate concentration was estimated by high resolution proton NMRS. Following baseline observations, the carotid arteries were occluded bilaterally and hypoxia and hypotension induced while NMR spectra were recorded continuously. After a variable period of hypoxia-ischaemia, the carotid clamps were released, normoxia and blood volume restored, and measurements continued for another 2-4 hours. During hypoxia-ischaemia, phosphocreatine (PCr) concentration fell to 41% and adenosine triphosphate (ATP) to 60% of control values with a corresponding increase of inorganic phosphate concentration. Anaerobic glycolysis was demonstrated by glucose consumption in excess of oxygen, and pHi fell from 7.13 + 0.02 (S.E.M.) in the baseline period to 6.28 & 0.09 during hypoxia-ischaemia. The severity of intracellular acidosis was related to the blood glucose concentration, but calculated lactate accumulations could not account entirely for the magnitude of pH, changes seen, assuming previously reported estimates of brain buffering capacity. During the recovery period, PCr, ATP concentrations and pHi returned to baseline values, but in one animal proton NMRS showed a persistent elevation of brain lactate at a time when pH, had returned to normal.

Impaired energy metabolism in the brains of newborn infants with increased cerebral echodensities. P.A. Hamilton, P.L. Hope, E. Cady, D.T. Delpy, J.S. Wyatt and E.O.R. Reynolds, Department of Paediatrics, University College London, London, U.K. Areas of increased echodensity detected in the brains of newborn infants by ultrasound scanning are often attributed to hypoxic-ischaemic injury. In surviving infants these echoes may evolve into cystic periventricular leucomalacia or other forms of cerebral atrophy, or they may disappear, apparently without adverse sequelae. We have used phosphorus nuclear magnetic resonance spectroscopy to determine whether cerebral energy metabolism was impaired in infants with increased echodensities and to see if the severity of impairment was related to subsequent cerebral atrophy. Twenty-eight preterm and term infants with increased echodensities and 18 comparable normal infants were studied. In the normal infants the phosphocreatine (PCr)/inorganic orthophosphate (Pi) ratio, an index of the energy state of the tissue, increased from 0.77 f 0.24 (95% confidence limits) at 28 weeks of gestational plus postnatal age to 1.09 + 0.24 at 42 weeks (r = 0.72 P < 0.001). All 13 infants with increased echodensities whose PCr/P, ratios remained within the normal range survived, although 3 with ratios towards the lower limit of normal developed cerebral atrophy. Nine of the 15 infants whose ratios fell below the normal range died and cerebral atrophy developed in the other 6. It is concluded that some but not all increased cerebral echodensities are associated with impaired energy metabolism, and that those infants with abnormal energy status are more likely to die or subsequently to develop cerebral atrophy.

Transport of amino acids in the blood-brain barrier in the newborn iamb. R.M. Gardiner, F. Brewster, P. Garrod and D.P. Brenton, Departments of Paediatrics and Human Metabolism, University College London, The Rayne Institute, University Street, London WClE 655, U.K. The transport of amino acids from blood to brain has been extensively investigated in the adult rat, and the existence of a facilitated transport system for large neutral amino acids is well established. Conflicting evidence exists concerning the existence of an alanine preferring