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    The effect of clomethiazole on plasma concentrations of interleukin-6, -8, -1beta, tumor necrosis factor-alpha, and neutrophil adhesion molecule expression during experimental extracorporeal circulation.

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    Authors
    Harmon, D
    Coleman, E
    Marshall, C
    Lan, W
    Shorten, G
    Affiliation
    Department of Anaesthesia & Intensive Care Medicine, Cork University Hospital,, University College Cork, Ireland.
    Issue Date
    2012-02-03T15:09:26Z
    MeSH
    Acid-Base Equilibrium
    Antigens, CD18/blood
    Blood Gas Analysis
    Cell Adhesion Molecules/*biosynthesis
    Chlormethiazole/*therapeutic use
    Extracorporeal Circulation/*adverse effects
    Humans
    Interleukin-1/blood
    Interleukin-6/blood
    Interleukin-8/blood
    Interleukins/*blood
    L-Selectin/biosynthesis
    Neuroprotective Agents/*therapeutic use
    Neutrophils/drug effects/*metabolism
    Tumor Necrosis Factor-alpha/*metabolism
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    Citation
    Anesth Analg. 2003 Jul;97(1):13-8, table of contents.
    Journal
    Anesthesia and analgesia
    URI
    http://hdl.handle.net/10147/208994
    PubMed ID
    12818935
    Abstract
    Clomethiazole (CMZ), a neuroprotective drug, has antiinflammatory actions. We investigated the effects of CMZ administration on plasma concentrations of interleukin (IL)-6, IL-8, IL-1beta, tumor necrosis factor-alpha, and neutrophil adhesion molecule expression during experimental extracorporeal circulation. Five healthy volunteers each donated 500 mL of blood, which was subsequently divided into equal portions. Identical extracorporeal circuits were simultaneously primed with donated blood (250 mL) and circulated for 2 h at 37 degrees C. CMZ was added to 1 of the circuits of each pair to achieve a total plasma concentration of 40 micro mol/L. Blood samples were withdrawn at (i) donation, (ii) immediately after addition of CMZ, and at (iii) 30, 60, 90, and 120 min after commencing circulation. Plasma concentrations of IL-6, IL-8, and tumor necrosis factor-alpha were less in the CMZ group compared with control after 60 min of circulation (2.2 [0.3] versus 3.2 [0.4], 14.9 [4.8] versus 21.9 [18.4], 63.3 [43.5] versus 132.2 [118.9] pg/mL, respectively, P < 0.05). After 120 min of circulation, neutrophils from CMZ-treated circuits showed significantly less CD18 expression compared with control (237.5 [97.4] versus 280.5 [111.5], P = 0.03). The addition of CMZ to experimental extracorporeal circuits decreases the inflammatory response. This effect may be of clinical benefit by decreasing inflammatory-mediated neurological injury during cardiopulmonary bypass. IMPLICATIONS: Enhancement of gamma-aminobutyric acid(A)-mediated effects by clomethiazole (CMZ) and associated neuroprotection has been established in animal models of cerebral ischemia. In an ex vivo study, we demonstrated antiinflammatory activity of CMZ in experimental extracorporeal circulation. This represents a potential neuroprotective mechanism of CMZ in patients undergoing coronary artery bypass surgery.
    Language
    eng
    ISSN
    0003-2999 (Print)
    0003-2999 (Linking)
    Collections
    Cork University Hospital

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