title: Effect of intraluminal application of tissue-type plasminogen activator on the fibrinolytic activity of experimental vein grafts.
abstract: OBJECTIVE
  The aim was to quantify the effect of intraluminally applied 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 techniques.
  
  
  METHODS
  A pig model of bilateral saphenous venin-carotid artery grafts was used. In each animal one side of the neck was grafted 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 perfused in situ for 2 h after implantation and before analysis. Changes in local fibrinolytic activity were quantified using fibrin plate techniques and specific chromogenic assays for tPA and urokinase (uPA) in tissue extract (n = 6 animals). Histological assessment was made using light and scanning microscopy (n = 4 animals).
  
  
  RESULTS
  Surgical preparation and distention significantly reduced the fibrinolytic activity of pig saphenous vein in terms of areas of lysis produced on fibrin plates (P < 0.05), tPA activity (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 less platelet and thrombus formation on histological examination.
  
  
  CONCLUSIONS
  Pretreatment of surgically harvested vein by intraluminal application of tPA before grafting enhances its fibrinolytic activity after exposure to 2 h perfusion in vivo. This technique requires further investigation to validate its potential as a means of providing local anticoagulation to veins implanted as arterial grafts thereby reducing the incidence of early graft thrombosis.
authors.affiliation: Bristol Royal Infirmary, United Kingdom.
authors.forename: M J
authors.initials: MJ
authors.lastname: Underwood
authors.forename: G
authors.initials: G
authors.lastname: Cooper
authors.forename: R
authors.initials: R
authors.lastname: More
authors.forename: A
authors.initials: A
authors.lastname: Coumbe
authors.forename: C
authors.initials: C
authors.lastname: Toner
authors.forename: P
authors.initials: P
authors.lastname: Reynolds
authors.forename: D
authors.initials: D
authors.lastname: de Bono
mesh_terms: D000818:Animals; D002339:Carotid Arteries / Q000601:surgery; D005342:Fibrinolysis / Q000187:drug effects; D010477:Perfusion; D012501:Saphenous Vein / Q000187:drug effects* / Q000637:transplantation*; D013552:Swine; D013927:Thrombosis / Q000517:prevention & control; D010959:Tissue Plasminogen Activator / Q000494:pharmacology*
chemical_list: D010959:Tissue Plasminogen Activator