title: Silyl-heparin bonding improves the patency and in vivo thromboresistance of carbon-coated polytetrafluoroethylene vascular grafts.
abstract: OBJECTIVE
  Our purpose was to improve the performance of carbon-coated expanded polytetrafluoroethylene vascular grafts by bonding the grafts with silyl-heparin, a biologically active heparin analog, using polyethylene glycol as a cross-linking agent. Material and method Silyl-heparin-bonded carbon-coated expanded polytetrafluoroethylene vascular grafts (Bard Peripheral Vascular, Tempe, Ariz), were evaluated for patency and platelet deposition 2 hours, 7 days, and 30 days after graft implantation in a canine bilateral aortoiliac artery model. Platelet deposition was determined by injection of autologous, (111)Indium-radiolabeled platelets, followed by a 2-hour circulation period prior to graft explantation. Histologic studies were performed on a 2-mm longitudinal strip of each graft (7-day and 30-day groups). Heparin activity of the explanted silyl-heparin grafts was determined by using an antithrombin-III based thrombin binding assay.
  
  
  RESULTS
  Overall chronic graft patency (7-day and 30-day groups) was 100% for the silyl-heparin bonded (16/16) grafts versus 68.75% for control (11/16) grafts (P =.043). Acute 2-hour graft patency was 100% for the silyl-heparin bonded (6/6) grafts versus 83.3% for control (5/6) grafts. Radiolabeled platelet deposition studies revealed a significantly lower amount of platelets deposited on the silyl-heparin grafts as compared with control grafts in the 30-day group (13.8 +/- 7.18 vs 28.4 +/- 9.73, CPM per cm2 per million platelets, mean +/- SD, P =.0451, Wilcoxon rank sum test). In the 2-hour group of dogs, a trend towards a lower deposition of platelets on the silyl-heparin grafts was observed. There was no significant difference in platelet deposition between the two grafts in the 7-day group. Histologic studies revealed a significant reduction in intraluminal graft thrombus present on the silyl-heparin grafts as compared with control grafts in the 30-day group of animals. In contrast, there was no difference in amount of graft thrombus present on both graft types in the 7-day group of dogs. Pre-implant heparin activity on the silyl-heparin bonded grafts was 2.0 IU/cm(2) (international units[IU]/cm(2)). Heparin activity remained present on the silyl-heparin grafts after explantation at all 3 time points (2 hours: above upper limit of assay, upper limit = 0.57, n = 6; 7 days: 0.106 +/- 0.015, n = 5; 30 days: 0.007 +/- 0.001, n = 5; mean +/- SD, IU/cm(2)).
  
  
  CONCLUSIONS
  Silyl-heparin bonding onto carbon-coated expanded polytetrafluoroethylene vascular grafts resulted in (1) improved graft patency, (2) increased in vivo graft thromboresistance, and (3) a significant reduction in intraluminal graft thrombus. This graft may prove to be useful in the clinical setting.
authors.affiliation: Department of Surgery, Loyola University Medical Center, Hines, Ill, USA.
authors.forename: James
authors.initials: J
authors.lastname: Laredo
authors.forename: Lian
authors.initials: L
authors.lastname: Xue
authors.forename: Vicki A
authors.initials: VA
authors.lastname: Husak
authors.forename: Joan
authors.initials: J
authors.lastname: Ellinger
authors.forename: Gundeep
authors.initials: G
authors.lastname: Singh
authors.forename: Paul O
authors.initials: PO
authors.lastname: Zamora
authors.forename: Howard P
authors.initials: HP
authors.lastname: Greisler
mesh_terms: D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology; D001807:Blood Vessel Prosthesis; D019917:Blood Vessel Prosthesis Implantation; D002244:Carbon; D020099:Coated Materials, Biocompatible; D004285:Dogs; D006083:Graft Occlusion, Vascular / Q000209:etiology / Q000517:prevention & control*; D006493:Heparin / Q000031:analogs & derivatives* / Q000494:pharmacology; D010973:Platelet Adhesiveness; D011138:Polytetrafluoroethylene; D013927:Thrombosis / Q000209:etiology / Q000517:prevention & control*; D014654:Vascular Patency
chemical_list: D000925:Anticoagulants; D020099:Coated Materials, Biocompatible; D002244:Carbon; D011138:Polytetrafluoroethylene; D006493:Heparin