J Korean Soc Plast Reconstr Surg.  1998 Oct;25(7):1258-1265.

Effect of cd18 monoclonal antibody on the rat island skin flap survival after various ischemic times

Abstract

Leukocyte adhesion to endothelium is one of the causes of reperfusion injury in the tissue even though it is usually pathophysiological crucial event in host defence mechanism. Neutrophil adhesion can cause endothelial damage by release of toxic products, such as oxidants, proteases, and produce plugging, local edema, hemorrhage and thrombosis. Blockade of CD18, the subunit of the leukocyte adhesion receptor complex(CD11/CD18), by using CD18 monoclonal antibody(CD18 mAb) has shown the reduction of reperfusion tissue injury recently. However, the effects of the antibody in the various ischemic duration have never been studied. That is why we studied the effects after 4, 6 and 8 hours of ischemia in the rat epigastric flap model. The 6 x 3 cm sized island skin flaps were elevated on the left abdomen. The epigastric arteries were occluded for 4, 6, and 8 hours, respectively and the flaps were sutured back to the beds with insertion of silastic sheets beneath the flap to prevent the nutritional supply by plasmatic imbibition. Fifteen minutes before reperfusion, the flaps were perfused with CD18 mAb(1mg/kg) in the experimental group and saline in the control group. The percentage of flap survival was assessed by computerized imaging analyzer on the seventh day after reperfusion and tissue biopsies were obtained for measurement of myeloperoxidase(MPO) level and histological study at 24 hours after reperfusion. The results were as follows: 1. Percentage of the flap survival was significantly increased in CD18 mAb-treated group compared with the control in 6 hour-ischemic group. But there were no significant differences between the antibody-treated group and the control in 4 and 8 hour-ischemic groups. 2. MPO activity was significantly decreased in the CD18 mAb-treated group compared with the control in 6 hour-ischemic group. But there were no significant differences between the antibody-treated group and the control in 4 and 8 hour-ischemic groups. 3. Histological findings showed almost no vessel wall migration nor extravascular accumulation of the neutrophils in both the groups of 4 hour-ischemic group. In the 6 hour-ischemic group, neutrophil migration and accumulation were significantly less in the CD18 mAb-treated group than those in the control. In 8 the hour-ischemic group, both the antibody-treated and control groups showed very prominent migration and accumulation of neutrophils in the extravascular area, but no significant difference was found between them. Based on the present findings, the 4 to 8 hours-ischemia is thought to be the critical time, in which the maximal inhibitory effect of CD18 mAb can be achieved in the rat island skin flap model. In the we want to cry CD18 mAb in a clinical situation , we have to consider the critical ischemic duration before we try, and we have to study more about critical ischemic duration in various tissues and organs.


MeSH Terms

Abdomen
Animals
Biopsy
Edema
Endothelium
Epigastric Arteries
Hemorrhage
Ischemia
Leukocytes
Neutrophils
Oxidants
Peptide Hydrolases
Rats*
Receptors, Leukocyte-Adhesion
Reperfusion
Reperfusion Injury
Skin*
Thrombosis
Oxidants
Peptide Hydrolases
Receptors, Leukocyte-Adhesion
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