Early remodeling of saphenous vein grafts: Proliferation, migration and apoptosis of adventitial and medial cells occur simultaneously with changes in graft diameter and blood flow

Background: This study was designed to determine how migration and prolifer ation of adventitial and medial cells correlate temporally with hemodynamic characteristics including changes in diameter and blood flow in vein graft s. Methods: Male mongrel dogs underwent end-to-side reversed saphenous vein bypass grafting across a ligated femoral artery. Hemodynamic parameters we re assessed by duplex ultrasound. Proliferating cells were labeled 24-48 h after grafting with 5-bromo-2'-deoxyuridine (BrdU). Grafts were removed on postoperative days 2, 5, 7 and 14. Immunohistochemistry was performed on gr aft sections with antibodies to nuclear antigen Ki-67 (MIB-1), BrdU and smo oth muscle cell markers. Apoptosis was identified by modified TUNEL stainin g. Proliferating/apoptotic cells were quantified digitally. Results: Mean l uminal cross-sectional area, blood flow and velocity increased from day 2 t o 7. Cell proliferation was evident in adventitia and media on day 2, maxim um on day 5 and decreased significantly by day 14. Apoptosis was maximum on day 5. Early proliferating cells (BrdU labeled) localized in the adventiti a and media on day 2 were more prevalent in the neointima on days 5-14 sugg esting inward migration. On day 2, proliferating cells stained positive onl y for vimentin. By days 5-14, proliferating cells stained for alpha -smooth -muscle actin, a phenotype characteristic of myofibroblasts. Conclusion: Th ese results indicate that cell proliferation and apoptosis occur simultaneo usly within the adventitia and media of the vein during the first week foll owing grafting, when changes in diameter and blood flow are greatest. In ad dition, proliferating adventitial cells subsequently mig rate inwards to co ntribute to the formation of neointima. Copyright (C) 2000 S. Karger AG, Ba sel.