Hypercarbia and Mild Hypothermia, Only When Not Combined, Improve Postischemic Bioenergetic Recovery in Neonatal Rat Brain Slices

• Published in: Journal of cerebral blood flow and metabolism Vol. 20; no. 3; pp. 612 - 619
• Main Authors: Tasker, Robert C., Sahota, Sati K., Williams, Stephen R.
• Format: Journal Article
• Language: English
• Published: London, England SAGE Publications 01-03-2000; Lippincott Williams & Wilkins; Sage Publications Ltd
• Subjects: Adenosine Triphosphate - metabolism; Animals; Animals, Newborn - physiology; Biological and medical sciences; Brain Ischemia - metabolism; Brain Ischemia - therapy; Carbon Dioxide - therapeutic use; Energy Metabolism; Hydrogen-Ion Concentration; Hypothermia, Induced; In Vitro Techniques; Intracellular Membranes - metabolism; Magnetic Resonance Spectroscopy; Medical sciences; Neurology; Phosphocreatine - metabolism; Rats; Vascular diseases and vascular malformations of the nervous system; Development; Neuroprotection; Nuclear magnetic resonance spectroscopy; Cerebral ischemia; Carbon dioxide; Hypothermia; Nervous system diseases; Rat; Rodentia; General anesthesia; Cardiovascular disease; Induced hypothermia; NMR spectrometry; Cerebral disorder; Vascular disease; Vertebrata; Experimental disease; Mammalia; Ischemia; Newborn animal; Central nervous system disease; Evolution; Induced hypercapnia; Cerebrovascular disease; Brain (vertebrata)
• ISSN: 0271-678X; 1559-7016
• DOI: 10.1097/00004647-200003000-00019

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°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 ∼20% in the recovery of β-ATP (P < 0.05). In combination, however, hypercarbia and hypothermia worsened recovery in ATP by ∼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.