This Article Full Text Full Text (PDF) All Versions of this Article: 38/5/1578    most recent STROKEAHA.106.473967v1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Richards, E. M. Articles by McKenna, M. C. Search for Related Content PubMed PubMed Citation Articles by Richards, E. M. Articles by McKenna, M. C. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB GLUCOSE GLUTAMIC ACID HYDROCHLORIDE Related Collections Animal models of human disease CPR and emergency cardiac care Acute myocardial infarction Brain Circulation and Metabolism Neuroprotectors

(Stroke. 2007;38:1578.)
© 2007 American Heart Association, Inc.

Original Contributions

Hyperoxic Reperfusion After Global Ischemia Decreases Hippocampal Energy Metabolism

Erica M. Richards, PhD; Gary Fiskum, PhD; Robert E. Rosenthal, MD; Irene Hopkins, MS Mary C. McKenna, PhD

From the Program in Neuroscience (E.M.R., G.F.), the Departments of Anesthesiology (E.M.R., G.F.) and Surgery, Program in Trauma (R.E.R.), and the Department of Pediatrics (I.H., M.C.M.) University of Maryland School of Medicine, Baltimore, Md.

Correspondence to Mary C. McKenna, Department of Pediatrics, 655 W Baltimore St, Room 13-019, Baltimore, MD 21201. E-mail mmckenna{at}umaryland.edu

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, [1-¹³C]glucose was infused, and at 2 hours, brains were rapidly removed and frozen. Extracted metabolites were analyzed by ¹³C nuclear magnetic resonance spectroscopy.

Results— Compared with nonischemic controls, the hippocampi from hyperoxic animals had elevated levels of unmetabolized ¹³C-glucose and decreased incorporation of ¹³C 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.

Key Words: ¹³C-glucose • pyruvate dehydrogenase • mitochondria • cardiac arrest • glutamate • energy metabolism