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Inhaled Carbon Monoxide Provides Cerebral Cytoprotection in Pigs

Authors: Vicki L. Mahan; David Zurakowski; Leo E. Otterbein; Frank A. Pigula;

Inhaled Carbon Monoxide Provides Cerebral Cytoprotection in Pigs

Abstract

Carbon monoxide (CO) at low concentrations imparts protective effects in numerous preclinical small animal models of brain injury. Evidence of protection in large animal models of cerebral injury, however, has not been tested. Neurologic deficits following open heart surgery are likely related in part to ischemia reperfusion injury that occurs during cardiopulmonary bypass surgery. Using a model of deep hypothermic circulatory arrest (DHCA) in piglets, we evaluated the effects of CO to reduce cerebral injury. DHCA and cardiopulmonary bypass (CPB) induced significant alterations in metabolic demands, including a decrease in the oxygen/glucose index (OGI), an increase in lactate/glucose index (LGI) and a rise in cerebral blood pressure that ultimately resulted in increased cell death in the neocortex and hippocampus that was completely abrogated in piglets preconditioned with a low, safe dose of CO. Moreover CO-treated animals maintained normal, pre-CPB OGI and LGI and corresponding cerebral sinus pressures with no change in systemic hemodynamics or metabolic intermediates. Collectively, our data demonstrate that inhaled CO may be beneficial in preventing cerebral injury resulting from DHCA and offer important therapeutic options in newborns undergoing DHCA for open heart surgery.

Subjects by Vocabulary

Library of Congress Subject Headings: lcsh:Medicine lcsh:Science lcsh:R lcsh:Q

Microsoft Academic Graph classification: law.invention law Medicine Neocortex Cytoprotection medicine.anatomical_structure Anesthesia Deep hypothermic circulatory arrest Ischemia Cardiopulmonary bypass business.industry Blood flow medicine.disease Blood pressure business Reperfusion injury

Keywords

Sus scrofa, Veterinary Anatomy and Physiology, Apoptosis, Cardiovascular, Molecular Cell Biology, Cellular Stress Responses, Neurons, Carbon Monoxide, Cardiovascular Surgery, Cardiopulmonary Bypass, Multidisciplinary, Cell Death, Brain, Animal Models, Neurology, Medicine, Female, Research Article, Animal Types, Large Animals, Animal Neuroanatomy, Model Organisms, Administration, Inhalation, In Situ Nick-End Labeling, Animals, Arterial Pressure, Lactic Acid, Biology, Oxygen, Glucose, Cytoprotection, Surgery, Veterinary Science

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    This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
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    influence
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    impulse
    This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
    Average
  • citations
    This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    21
    popularity
    This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
    Top 10%
    influence
    This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    Average
    impulse
    This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
    Average
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citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
21
Top 10%
Average
Average
Green
gold
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NIH| Endogenous Gas Molecules As Transcription Factors
Project
  • Funder: National Institutes of Health (NIH)
  • Project Code: 5R01GM088666-02
  • Funding stream: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
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NIH| HemeOxygenase-1 and Transplant Tolerance
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  • Funder: National Institutes of Health (NIH)
  • Project Code: 1R56AI092272-01A1
  • Funding stream: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
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