Hyperoxic reperfusion after global ischemia decreases hippocampal energy metabolism

Erica M. Richards, Gary Fiskum, Robert E. Rosenthal, Irene Hopkins, Mary C. McKenna

Research output: Contribution to journalArticlepeer-review

Abstract

BACKGROUND AND PURPOSE - Previous reports indicate that compared with normoxia, 100% ventilatory O2 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% O2 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% O2 (hyperoxic) or 21% to 30% O2 (normoxic). At 30 minutes reperfusion, [1-C]glucose was infused, and at 2 hours, brains were rapidly removed and frozen. Extracted metabolites were analyzed by C nuclear magnetic resonance spectroscopy. RESULTS - Compared with nonischemic controls, the hippocampi from hyperoxic animals had elevated levels of unmetabolized C-glucose and decreased incorporation of 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 O2.

Original languageEnglish (US)
Pages (from-to)1578-1584
Number of pages7
JournalStroke
Volume38
Issue number5
DOIs
StatePublished - May 2007
Externally publishedYes

Keywords

  • C-glucose
  • Cardiac arrest
  • Energy metabolism
  • Glutamate
  • Mitochondria
  • Pyruvate dehydrogenase

ASJC Scopus subject areas

  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine
  • Advanced and Specialized Nursing

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