Hyperoxic reperfusion after global ischemia decreases hippocampal energy metabolism.
OBJECTIVE
Previous reports indicate that compared with normoxia, 100% ventilatory O(2) during early reperfusion after global cerebral ischemia decreases hippocampal pyruvate dehydrogenase activity and increases neuronal death. However, current standards of care after cardiac arrest encourage the use of 100% O(2) during resuscitation and for an undefined period thereafter. Using a clinically relevant canine cardiac arrest model, in this study we tested the hypothesis that hyperoxic reperfusion decreases hippocampal glucose metabolism and glutamate synthesis.


METHODS
After 10 minutes of cardiac arrest, animals were resuscitated and ventilated for 1 hour with 100% O(2) (hyperoxic) or 21% to 30% O(2) (normoxic). At 30 minutes reperfusion, [1-(13)C]glucose was infused, and at 2 hours, brains were rapidly removed and frozen. Extracted metabolites were analyzed by (13)C nuclear magnetic resonance spectroscopy.


RESULTS
Compared with nonischemic controls, the hippocampi from hyperoxic animals had elevated levels of unmetabolized (13)C-glucose and decreased incorporation of (13)C into all isotope isomers of glutamate. These findings indicate impaired neuronal metabolism via the pyruvate dehydrogenase pathway for carbon entry into the tricarboxylic acid cycle and impaired glucose metabolism via the astrocytic pyruvate carboxylase pathway. No differences were observed in the cortex, indicating that the hippocampus is more vulnerable to metabolic changes induced by hyperoxic reperfusion.


CONCLUSIONS
These results represent the first direct evidence that hyperoxia after cardiac arrest impairs hippocampal oxidative energy metabolism in the brain and challenge the rationale for using excessively high resuscitative ventilatory O(2).
Richards
Erica M
EM
Program in Neuroscience, the Department of Anesthesiology, University of Maryland School of Medicine, Baltimore, MD, USA.
Fiskum
Gary
G
Rosenthal
Robert E
RE
Hopkins
Irene
I
McKenna
Mary C
MC
D000818:Animals; D002545:Brain Ischemia / Q000209:etiology / Q000503:physiopathology*; D016887:Cardiopulmonary Resuscitation; D004285:Dogs; D004734:Energy Metabolism / Q000502:physiology*; D005260:Female; D005947:Glucose / Q000378:metabolism; D018698:Glutamic Acid / Q000096:biosynthesis; D006323:Heart Arrest / Q000150:complications / Q000628:therapy*; D006624:Hippocampus / Q000378:metabolism*; D018384:Oxidative Stress; D010102:Oxygen Inhalation Therapy / Q000379:methods*; D015427:Reperfusion Injury / Q000209:etiology / Q000503:physiopathology* / Q000517:prevention & control; D012121:Respiration, Artificial
D018698:Glutamic Acid; D005947:Glucose