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    Ketamine immunomodulation during endotoxemia

    DeClue, Amy E.
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    [PDF] research.pdf (293.1Kb)
    Date
    2007
    Format
    Thesis
    Metadata
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    Abstract
    [ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT AUTHOR'S REQUEST.] Previous studies have shown that ketamine attenuates endotoxin (LPS)-induced production of tumor necrosis factor (TNF)-[alpha] in murine models. Because TNF-[alpha] is a key mediator of the systemic and pulmonary inflammatory response to infection, we hypothesized that ketamine would ameliorate LPS-induced acute lung injury (ALI) in rats and prevent the hemodynamic and immunologic alterations in dogs. Forty male CD rats were divided into 4 treatment groups: control, ketamine, LPS and LPS+ ketamine. Rats were euthanized at either 1 or 6 hours after LPS administration for determination of serum TNF-[alpha] activity or pulmonary evaluation. Ketamine treatment blunted LPSinduced serum TNF-[alpha] activity but did not ameliorate the pulmonary histopathologic changes associated with endotoxemia. For the second study, nine dogs were randomized to either ketamine or placebo treatment groups in a cross-over design. At 30 min, LPS was administered. Heart rate (HR), systolic arterial blood pressure (SAP), plasma TNF-[alpha] activity and white blood cell (WBC) counts were evaluated. Dogs in the ketamine group had significantly lower HR and peak plasma TNF-[alpha] activity after LPS administration versus placebo. There were no differences detected between treatment groups for SAP or white blood cell counts. Based on these data, while ketamine ameliorates TNF-[alpha] production in rats and dogs, it is unlikely to have a clinically important impact on the development of acute lung injury, perturbations in WBC count or SAP during Gram negative sepsis.
    URI
    https://hdl.handle.net/10355/6276
    https://doi.org/10.32469/10355/6276
    Degree
    M.S.
    Thesis Department
    Veterinary medicine and surgery (MU)
    Rights
    Access is limited to the campuses of the University of Missouri.
    Collections
    • 2007 MU theses - Access restricted to UM
    • Veterinary Medicine and Surgery electronic theses and dissertations (MU)

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