EFFECT OF INTRALUMINAL APPLICATION OF TISSUE-TYPE PLASMINOGEN-ACTIVATOR ON THE FIBRINOLYTIC-ACTIVITY OF EXPERIMENTAL VEIN GRAFTS

Objective: The aim was to quantify the effect of intraluminally applie d tissue-type plasminogen activator (tPA) on the fibrinolytic activity of experimental vein grafts and assess the effect of pretreatment of the vein on early platelet and thrombus formation using histological t echniques. Methods: A pig model of bilateral saphenous venin - carotid artery grafts was used. In each animal one side of the neck was graft ed using vein distended to 230 mm Hg and pretreated with tPA (1 mg.ml( -1)) for a period of 15 min before grafting (treated graft). The other side of the neck was grafted using distended vein treated with Krebs buffer (control graft). All grafts were perfused in situ for 2 h after implantation and before analysis. Changes in local fibrinolytic activ ity were quantified using fibrin plate techniques and specific chromog enic assays for tPA and urokinase (uPA) in tissue extract (n = 6 anima ls). Histological assessment was made using light and scanning microsc opy (n = 4 animals). Results: Surgical preparation and distention sign ificantly reduced the fibrinolytic activity of pig saphenous vein in t erms of areas of lysis produced on fibrin plates (P < 0.05), tPA activ ity (P < 0.05), and uPA activity (P < 0.05). Pretreatment of distended vein with tPA before grafting significantly enhanced its fibrinolytic activity after 2 h perfusion compared to control (untreated) grafts, as assessed by areas of lysis on fibrin plates (P < 0.05) and specific tPA activity (P < 0.05). Treated grafts also showed qualitatively les s platelet and thrombus formation on histological examination. Conclus ions: Pretreatment of surgically harvested vein by intraluminal applic ation of tPA before grafting enhances its fibrinolytic activity after exposure to 2 h perfusion in vivo. This technique requires further inv estigation to validate its potential as a means of providing local ant icoagulation to veins implanted as arterial grafts thereby reducing th e incidence of early graft thrombosis.