Hypercarbia and mild hypothermia, only when not combined, improve postischemic bioenergetic recovery in neonatal rat brain slices

In the immature brain, postischemic metabolism may be influenced beneficial ly by the effect of inducing hypercarbia or hypothermia. With use of P-31 n uclear magnetic resonance spectroscopy, intracellular pH (pH,) and cellular energy metabolites in ex vivo neonatal rat cerebral cortex were measured b efore, during, and after substrate and oxygen deprivation in in vitro ische mia. Early postischemic hypothermia (fall in temperature -3.2 +/- 1.0 degre es C) delayed the normalization of pi-Ii after ischemia by inducing an acid shift in pH(i) (P < 0.01). Postischemic hypercarbia (Krebs-Henseleit bicar bonate buffer equilibrated with 10% carbon dioxide in oxygen) and hypotherm ia induced separate, but potentially additive, reversible decreases in pH,, each of approximately -0.16 pH unit (P < 0.05). When these postischemic pe rturbations were applied in isolation, there was significant improvement of similar to 20% in the recovery of beta-ATP (P < 0.05). In combination, how ever, hypercarbia and hypothermia worsened recovery in ATP by similar to 20 % (P < 0.05). In control tissue, which had not been exposed to ischemia, AT P content was also significantly reduced by co-administration of the two tr eatments (P < 0.05), an effect that persisted even after discontinuing the perturbing conditions. Therefore, in this vascular-independent neonatal pre paration, early postischemic modulation of metabolism by hypercarbia or hyp othermia appears to confer improved bioenergetic recovery, but only if they are not administered together.