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 beneficially by the effect of inducing hypercarbia or hypothermia. With use of 31P nuclear magnetic resonance spectroscopy, intracellular pH (pHi) and cellular energy metabolites in ex vivo neonatal rat cerebral cortex were measured before, during, and after substrate and oxygen deprivation in in vitro ischemia. Early postischemic hypothermia (fall in temperature -3.2 +/- 1.0 degrees C) delayed the normalization of pHi after ischemia by inducing an acid shift in pHi (P < 0.01). Postischemic hypercarbia (Krebs-Henseleit bicarbonate buffer equilibrated with 10% carbon dioxide in oxygen) and hypothermia induced separate, but potentially additive, reversible decreases in pHi, each of approximately -0.16 pH unit (P < 0.05). When these postischemic perturbations were applied in isolation, there was significant improvement of approximately 20% in the recovery of beta-ATP (P < 0.05). In combination, however, hypercarbia and hypothermia worsened recovery in ATP by approximately 20% (P < 0.05). In control tissue, which had not been exposed to ischemia, ATP content was also significantly reduced by co-administration of the two treatments (P < 0.05), an effect that persisted even after discontinuing the perturbing conditions. Therefore, in this vascular-independent neonatal preparation, early postischemic modulation of metabolism by hypercarbia or hypothermia appears to confer improved bioenergetic recovery, but only if they are not administered together.
Tasker
R C
RC
Department of Paediatrics, University of Cambridge School of Clinical Medicine, UK.
Sahota
S K
SK
Williams
S R
SR
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn / Q000502:physiology; D002545:Brain Ischemia / Q000378:metabolism* / Q000628:therapy*; D002245:Carbon Dioxide / Q000627:therapeutic use*; D004734:Energy Metabolism; D006863:Hydrogen-Ion Concentration; D007036:Hypothermia, Induced; D066298:In Vitro Techniques; D007425:Intracellular Membranes / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D010725:Phosphocreatine / Q000378:metabolism; D051381:Rats
D010725:Phosphocreatine; D002245:Carbon Dioxide; D000255:Adenosine Triphosphate