title: Boundary layer infusion of heparin prevents thrombosis and reduces neointimal hyperplasia in venous polytetrafluoroethylene grafts without systemic anticoagulation.
abstract: OBJECTIVE
  Recently, we designed and characterized a novel polytetrafluoroethylene-based local drug delivery device that selectively concentrates infused pharmacologic agents specifically within those blood layers adjacent to the graft wall and at downstream anastomotic sites. In this study we locally administered heparin with this approach and evaluated its effect on graft patency and neointimal hyperplasia formation in a rabbit model of inferior vena cava replacement.
  
  
  METHODS
  Twelve animals were evenly assigned either to a control group infused with saline solution or to a treatment group infused with heparin for 14 days. Bromodeoxyuridine labeling was used to assess vascular cell proliferation.
  
  
  RESULTS
  All grafts in the control group were occluded at 14 days. All grafts in the heparin-treated group remained patent, although there was no significant difference in systemic activated partial thromboplastin time measurements taken before and during the infusion of heparin (p > 0.5). In the treatment group, heparin reduced neointimal thickness, neointimal area, and the bromodeoxyuridine labeling index by 88%, 95%, and 72%, respectively (p < 0.01), at the locally treated downstream anastomosis as compared with the untreated upstream anastomosis.
  
  
  CONCLUSIONS
  These data demonstrate that the local boundary layer infusion of heparin significantly increases overall inferior vena cava graft patency (p = 0.014) and markedly reduces downstream anastomotic neointimal hyperplasia and cell proliferation. This approach may represent an attractive strategy for antithrombotic therapy in venous replacement with synthetic graft materials.
authors.affiliation: Department of Surgery, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: C
authors.initials: C
authors.lastname: Chen
authors.forename: S R
authors.initials: SR
authors.lastname: Hanson
authors.forename: A B
authors.initials: AB
authors.lastname: Lumsden
mesh_terms: D000818:Animals; D001807:Blood Vessel Prosthesis; D002455:Cell Division / Q000187:drug effects; D016503:Drug Delivery Systems; D006493:Heparin / Q000008:administration & dosage*; D006965:Hyperplasia / Q000517:prevention & control; D015918:Infusion Pumps, Implantable; D008297:Male; D011138:Polytetrafluoroethylene; D011817:Rabbits; D013927:Thrombosis / Q000517:prevention & control*; D017539:Tunica Intima / Q000473:pathology*; D014654:Vascular Patency; D014682:Vena Cava, Inferior / Q000473:pathology / Q000601:surgery*
chemical_list: D011138:Polytetrafluoroethylene; D006493:Heparin