Vasoactive effects of fibrinogen on saphenous vein.

Normal plasma fibrinogen concentrations are critical to haemostasis. Higher fibrinogen concentrations are associated with increasing risk of atherosclerotic disease and with graft stenosis and occlusion after saphenous vein bypass surgery. Vein graft stenosis is characterized by the localized proliferation of intimal smooth muscle cells, causing narrowing of the graft with increased risk of thrombotic occlusion. In rabbit arteries, fibrinopeptide B is reported to have both vasoconstrictor and mitogenic properties. We report here that fibrinopeptides had no vasoactive effects on saphenous vein rings; however, fibrinogen (0-2 microM) affected an endothelium-dependent relaxation, followed by recontraction at higher concentrations. The fibrinogen-mediated relaxation was inhibited by K+-channel blockers and antibodies to ICAM-1. Coupled signalling pathways for the synthesis of vasoactive mediators and mitogens could underlie the association between fibrinogen and the development of vein graft pathology.

The influence of fibrinogen concentration on the development of vein graft stenoses.

OBJECTIVE: The aim of this study was to identify factors associated with the development of graft stenoses in the first year after bypass. DESIGN AND SETTING: Between January 1992 and April 1993, 75 consecutive patients undergoing distal vein bypass surgery were entered into a graft surveillance programme at Charing Cross Hospital. The grafts (n = 79) were surveyed by colour flow Doppler ultrasonography at 7 days, 3, 6, 9 and 12 months and the site of stenoses (> 50%) recorded. Position of the distal anastomosis, graft type (in situ or reverse) and clinical history were recorded. At the 3-month surveillance a blood sample was taken for the estimation of smoking markers, lipids and fibrinogen. RESULTS: The site of the distal anastomosis was to the suprageniculate popliteal in nine, infrageniculate popliteal in 32 and tibio/peroneal vessels in 38 cases. In the first month following bypass there were six deaths, giving a 30 day mortality of 7.5%, three patients were lost to follow up, seven grafts occluded, three were replaced by PTFE, four patients underwent amputation and one patient had a redo vein graft. In the remaining grafts 20/63 (32%) developed stenoses within the first year after bypass. The development of a graft stenosis was not associated with sex, diabetic status, site of distal anastomosis, graft type or serum lipids. Multiple regression analysis identified only one factor associated significantly with the development of vein graft stenosis: fibrinogen concentration (p = 0.003). Life table analysis showed that after 1 year only 46% of grafts remained free of stenoses in patients with above median fibrinogen concentrations compared with 84% of grafts in patients with below median fibrinogen concentrations, p = 0.009. CONCLUSIONS: Increased plasma fibrinogen concentration is a potent risk factor for the development of vein graft stenosis. These results prompt consideration of the role of fibrinogen in stimulating smooth muscle cell proliferation in the stenotic lesion.