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.

Hdl Handle:
http://hdl.handle.net/10147/208994
Title:
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.
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.
Citation:
Anesth Analg. 2003 Jul;97(1):13-8, table of contents.
Journal:
Anesthesia and analgesia
Issue Date:
3-Feb-2012
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added to 1 of the circuits of each pair to achieve a total plasma concentration of 40 micro mol/L. Blood samples were withdrawn at (i) donation, (ii) immediately after addition of CMZ, and at (iii) 30, 60, 90, and 120 min after commencing circulation.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
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
ISSN:
0003-2999 (Print); 0003-2999 (Linking)

Full metadata record

DC FieldValue Language
dc.contributor.authorHarmon, Den_GB
dc.contributor.authorColeman, Een_GB
dc.contributor.authorMarshall, Cen_GB
dc.contributor.authorLan, Wen_GB
dc.contributor.authorShorten, Gen_GB
dc.date.accessioned2012-02-03T15:09:26Z-
dc.date.available2012-02-03T15:09:26Z-
dc.date.issued2012-02-03T15:09:26Z-
dc.identifier.citationAnesth Analg. 2003 Jul;97(1):13-8, table of contents.en_GB
dc.identifier.issn0003-2999 (Print)en_GB
dc.identifier.issn0003-2999 (Linking)en_GB
dc.identifier.pmid12818935en_GB
dc.identifier.urihttp://hdl.handle.net/10147/208994-
dc.description.abstractClomethiazole (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.en_GB
dc.language.isoengen_GB
dc.subject.meshAcid-Base Equilibriumen_GB
dc.subject.meshAntigens, CD18/blooden_GB
dc.subject.meshBlood Gas Analysisen_GB
dc.subject.meshCell Adhesion Molecules/*biosynthesisen_GB
dc.subject.meshChlormethiazole/*therapeutic useen_GB
dc.subject.meshExtracorporeal Circulation/*adverse effectsen_GB
dc.subject.meshHumansen_GB
dc.subject.meshInterleukin-1/blooden_GB
dc.subject.meshInterleukin-6/blooden_GB
dc.subject.meshInterleukin-8/blooden_GB
dc.subject.meshInterleukins/*blooden_GB
dc.subject.meshL-Selectin/biosynthesisen_GB
dc.subject.meshNeuroprotective Agents/*therapeutic useen_GB
dc.subject.meshNeutrophils/drug effects/*metabolismen_GB
dc.subject.meshTumor Necrosis Factor-alpha/*metabolismen_GB
dc.titleThe effect of clomethiazole on plasma concentrations of interleukin-6, -8, -1beta, tumor necrosis factor-alpha, and neutrophil adhesion molecule expression during experimental extracorporeal circulation.en_GB
dc.contributor.departmentDepartment of Anaesthesia & Intensive Care Medicine, Cork University Hospital,, University College Cork, Ireland.en_GB
dc.identifier.journalAnesthesia and analgesiaen_GB
dc.description.provinceMunster-

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