Monocyte adhesion to human vein grafts: A marker for occult intraoperativeinjury?

dObjective: Monocyte adhesion to the vessel wall is believed to be an impor tant initiating event in atherosclerosis and intimal hyperplasia. We hypoth esized that occult intraoperative vein injury induces an immediate increase in monocyte adhesion that may be critical to the development of vein graft disease. Methods: Vein segments were obtained from patients (n = 23) undergoing lowe r extremity bypass. The initial segment (V1, n = 17) was excised immediatel y at the time of conduit harvest. A second segment (V2, n = 23) was obtaine d from the distal conduit just before performing the distal anastomosis. Se gments were incubated with radiolabeled THP-1 cells (monocytoid cell line) for 1 hour at 37 degreesC, then rinsed and solubilized for determination of bound radioactivity. In a subset of grafts (n = 4), THP-1 cells were prein cubated with monoclonal antibody (mAB) 7E3 (which binds to the monocyte int egrin Mac-1 at its fibrinogen [Fg]-binding site) or control (mAB 14E11). Fg deposition and endothelial coverage were. evaluated by immunohistochemistr y (n = 10). Statistical analysis was performed using the paired t test and analysis of variance. Follow-up graft patency data were obtained and correl ated with adhesion values using an exact test (StatXact, Cytel Software, Ca mbridge, Mass). Results. Monocyte adhesion was significantly increased after surgical manip ulation (V1, 2400 +/- 770 versus V2, 7343 +/- 1555 cells/cm(2); P < .02). F g deposition was abundant in V2 sections and not seen in Vl. Monocyte adhes ion to V2 segments was significantly reduced (58% of control, P < .01) by 7 E3 treatment. Graft follow-up was complete with a mean interval of 11 month s. Higher V2 adhesion values were associated with occluded grafts (P = .07) . The median value for the six occluded grafts was 6234 cells/cm(2) versus 3892 cells/cm(2) for the 17 patent grafts. Conclusions. Monocyte adhesion to the vein wall is immediately increased af ter surgical manipulation and is inhibited by mAB 7E3. Early monocyte adhes ion to vein grafts is likely to involve interactions between Mac-1 and Pg. Heightened levels of monocyte adhesion at implantation may be a marker for subsequent vein graft failure.