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.
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added to 1 of the circuits of each pair to achieve a total plasma concentration of 40 micro mol/L. Blood samples were withdrawn at (i) donation, (ii) immediately after addition of CMZ, and at (iii) 30, 60, 90, and 120 min after commencing circulation.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.


CONCLUSIONS
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.
Harmon
D
D
Department of Anaesthesia & Intensive Care Medicine, Cork University Hospital, University College Cork, Ireland.
Coleman
E
E
Marshall
C
C
Lan
W
W
Shorten
G
G
D000136:Acid-Base Equilibrium; D001784:Blood Gas Analysis; D018821:CD18 Antigens / Q000097:blood; D015815:Cell Adhesion Molecules / Q000096:biosynthesis*; D002719:Chlormethiazole / Q000627:therapeutic use*; D005112:Extracorporeal Circulation / Q000009:adverse effects*; D006801:Humans; D007375:Interleukin-1 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D016209:Interleukin-8 / Q000097:blood; D007378:Interleukins / Q000097:blood*; D019041:L-Selectin / Q000096:biosynthesis; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D018821:CD18 Antigens; D015815:Cell Adhesion Molecules; D007375:Interleukin-1; D015850:Interleukin-6; D016209:Interleukin-8; D007378:Interleukins; D018696:Neuroprotective Agents; D014409:Tumor Necrosis Factor-alpha; D002719:Chlormethiazole; D019041:L-Selectin