title: Effect of locally applied tissue-type plasminogen activator on venous fibrinolytic activity: in vitro and in vivo investigations.
abstract: OBJECTIVE
  The aim was to see if topically applied tissue-type plasminogen activator (tPA) would enhance the fibrinolytic activity of saphenous vein prepared before coronary artery surgery, persist in the vessel wall after perfusion, and reduce thrombus formation after vascular injury.
  
  
  METHODS
  Varying doses of tPA were applied to the intimal surface of the saphenous vein obtained from patients before coronary artery surgery. After flushing, biopsies were incubated on fibrin plates and areas of lysis quantified. Samples treated with tPA (1 mg.ml-1) were perfused in vitro for 30 minutes. Fibrinolytic activity was assessed on fibrin plates and tPA activity (in tissue extract) measured with chromogenic assays. The effect of locally applied tPA on thrombus formation was quantified with a rat vena cava model based on vascular injury and stasis.
  
  
  RESULTS
  Local application of 1 mg.ml-1 tPA enhanced fibrinolysis under static conditions [median (interquartile range) of diameter of lysis.mm-1 (n = 8 both groups), treated vein 16.5 (14.1-17.9), control 8.5 (5.75-10.37) (p < 0.05)]. This enhanced activity was retained after in vitro perfusion [median (interquartile range) of areas of lysis.mm-2 (n = 8 all groups), treated vein 170.8 (132.8-205.1), control (unperfused) 69.5 (45.2-87.6), perfused (untreated) 76.7 (58.3-98.9) (p < 0.01)]. Specific tPA activity in these samples was also increased (p < 0.05). Local application of tPA (1 mg.ml-1) to damaged rat vena cava reduced subsequent thrombus formation [median thrombus weight.mg-1 (interquartile range) (n = 8), tPA treated 2.5 (0.25-5.75), control 38.5 (32-43) (p < 0.001)].
  
  
  CONCLUSIONS
  Locally applied tPA enhances the fibrinolytic activity of damaged vessel wall, persists after perfusion, and reduces thrombus formation after vascular injury. This method of treating conduits before their use as vascular grafts merits further study to see if it is effective in reducing early graft thrombosis while maintaining systemic haemostasis.
authors.affiliation: Academic Department of Cardiology, Glenfield General Hospital, Leicester, United Kingdom.
authors.forename: M J
authors.initials: MJ
authors.lastname: Underwood
authors.forename: R S
authors.initials: RS
authors.lastname: More
authors.forename: A H
authors.initials: AH
authors.lastname: Gershlick
authors.forename: D P
authors.initials: DP
authors.lastname: de Bono
mesh_terms: D000818:Animals; D001026:Coronary Artery Bypass; D046508:Culture Techniques; D005342:Fibrinolysis / Q000187:drug effects*; D006801:Humans; D010477:Perfusion; D051381:Rats; D017208:Rats, Wistar; D012501:Saphenous Vein / Q000187:drug effects / Q000293:injuries / Q000502:physiology* / Q000648:ultrastructure; D013927:Thrombosis / Q000517:prevention & control; D010959:Tissue Plasminogen Activator / Q000494:pharmacology*
chemical_list: D010959:Tissue Plasminogen Activator