Nitric oxide–releasing biopolymers inhibit thrombus formation in a sheep model of arteriovenous bridge grafts

Abstract

Nitric oxide (NO), produced by normal vascular endothelial cells, reduces platelet aggregation and thrombus formation. NO-releasing biopolymers have the potential to prolong vascular graft and stent patency without adverse systemic vasodilation. 5-mm polyurethane vascular grafts coated with a polymer containing the NO-donor dialkylhexanediamine diazeniumdiolate were implanted for 21 days in a sheep arteriovenous bridge-graft model. Eighty percent (4/5) of grafts coated with the NO-releasing polymer remained patent through the 21 day implantation period, compared to fifty percent (2/4) of sham-coated grafts and no (0/3) uncoated grafts. Thrombus-free surface area (+/-SEM) of explanted grafts was significantly increased in NO-donor coated grafts (98.2% +/- 0.9%) compared with sham-coated (79.2% +/- 8.6%) and uncoated (47.2% +/- 5.4%) grafts ( P = .00046). Examination of the graft surface showed no adherent thrombus or platelets and no inflammatory cell infiltration in NO-donor coated grafts, while control grafts showed adherent complex surface thrombus consisting of red blood cells in an amorphous fibrin matrix, as well as significant red blood cell and inflammatory cell infiltration into the graft wall. In this study we determined that local NO release from the luminal surface of prosthetic vascular grafts can reduce thrombus formation and prolong patency in a model of prosthetic arteriovenous bridge grafts in adult sheep. These findings may translate into improved function and improved primary patency rates in small-diameter prosthetic vascular grafts.