Abstract
Definition of the elements governing leukocyte adhesion to the microvascular endothelium may lead to new forms of treatment for reperfusion injury. The objectives of this study, employing a porcine latissimus dorsi flap reperfusion model, were (1) to characterize the expression of E- and L-selectin adhesion molecules and (2) to test for a possible benefit of E- and L-selectin blockade in the preceding experimental setting. In experiment 1, full-thickness biopsies were collected sequentially over an 8-hour ischemia and subsequent 6-hour reperfusion period. Immunocytochemistry was performed with monoclonal antibody EL-246, an antibody that crossreacts with both E- and L-selectin. In experiment 2, the binding of EL-246 to L-selectin on circulating porcine neutrophils was determined by flow cytometric analysis. In experiment 3, in situ hybridization was performed using complementary RNA probes for detection of endothelial E-selectin mRNA. In experiment 4, bilateral flaps were elevated in six pigs and subjected to 8 hours of arterial ischemia followed by 20 hours of reperfusion. Flaps on each animal were randomly assigned to receive either treatment with a continuous local intraarterial infusion of EL-246 (1 mg per flap) or solvent ...Continue Reading
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