MONOCYTE INFILTRATION INTO VENOUS VALVES

Purpose: Greater saphenous veins removed at surgery for correction of venous dysfunction have few valves. Those that are present may be shru nken, deformed, or monocuspid. This study was carried out to determine whether leukocyte infiltration is associated with valve damage. Metho ds: Seventeen specimens were removed at surgery front five men and eig ht women (age, 29 to 80 years). These consisted of the proximal 15 cm of the duplex-confirmed, refluxing proximal greater saphenous vein, on e proximal lesser saphenous vein, and one midportion of greater saphen ous vein. The severity of venous stasis in each patient limb was class ified by the CLAP formula.(1) Twelve were class 2, two were class 3, a nd three were class 4. Control specimens were obtained from patients w ho underwent coronary artery bypass grafting. These were two men and t wo women, ages 72, 66, 62, and 60 years, free of venous insufficiency, with the specimens obtained from the proximal saphenous vein. Two of the control specimens contained venous valves corresponding to the tes t specimens. Longitudinal 10 mu m paraffin sections were labeled with anti-CD64 monoclonal antibody, specific for tissue monocytes and macro phages, and studied by light microscopy. Five regions were chosen for quantification of the leukocyte infiltrate. Cells were categorized and counted directly. Volume proportions were calculated using stereologi c techniques. Results: Three of seven specimens studied for morphologi c changes had clearly shortened valve leaflets. Collagen degeneration was noted in all seven specimens. Leaflets had essentially disappeared in three and were shortened to 100 to 2100 mu m in five. Specific leu kocyte staining was accomplished on 10 additional specimens. All speci mens showed monocyte/macrophage infiltration in valve leaflets and ven ous wall. These were more numerous in the valve sinus and proximal wal l both on and under the endothelium. Control specimens showed no monoc yte/macrophage infiltration. Conclusions: These observations suggest t hat venous valve damage in refluxing saphenous veins is associated wit h a leukocyte (monocyte/macrophage) infiltrate. Cell activation and fl uid dynamic factors, such as eddies recirculation, and stasis in the v alve sinus may be a part of the process of leukocyte penetration of th e endothelium. The magnitude of leukocyte infiltration in the vein wal l and in the base of the valve leaflet may be important in the genesis of primary venous dysfunction.