Background: The timing for initiation of effective antithrombotic therapy relative to the onset of arterial thrombosis may influence outcomes. This report investigates the hypothesis that early administration of heparin anticoagulation relative to the onset of thrombotic occlusion will effect a reduction in occlusion. Methods: A standard rat model of experimental thrombosis induction was used, injuring the carotid artery exposure with FeCl₃-saturated filter paper, followed by flow monitoring for onset of occlusion and subsequent embolization events. Intravenous heparin administration (200 units/mL) was timed relative to the initiation of injury or onset of near occlusion, compared with controls (no heparin administration). Results: No occlusion was found for delivery of heparin 5 min prior to thrombus induction, whereas all vessels occluded without heparin. Unstable (embolic) thrombi were seen with heparin given at or shortly after initial occlusion. Only 9% (1/11) of the vessels had permanent occlusion when heparin was given at the time of thrombotic onset (p < 0.0001 vs. unheparinized), while 50% occluded when heparin was delayed by 5 min (p > 0.05). Conclusions: These findings provide evidence that antithrombotic therapy may need to be administered prior to the onset of anticipated loss of patency, with less effectiveness when given after occlusion has occurred.

Severe peripheral arterial disease (PAD) is often treated with surgical bypass grafting using autologous vein. When veins are unavailable, small-diameter expanded polytetrafluoroethylene (ePTFE) grafts are used but are associated with long-term poor performance. To address this, we developed poly(1,8-octanediol-co-citrate-co-ascorbate) (POCA) elastomer coatings for small-diameter ePTFE grafts that indirectly release nitric oxide via decomposition of circulating S-nitrosothiols (RSNO). Graft in vivo efficacy was assessed using a guinea pig aortic interposition model to evaluate neointimal formation. After 4 weeks, POCA-Grafts demonstrated significantly less occlusion compared to uncoated ePTFE grafts (16.8 % versus 29.7 %, p < 0.0005) and POC (poly(1,8-octanediol-co-citrate))-Grafts without ascorbate (16.8 % versus 19.9 %, p < 0.005). POCA-Grafts showed a 1.6-fold increase in endothelial cell coverage and significantly reduced leukocyte and macrophage infiltration compared to uncoated ePTFE grafts, particularly in female animals. These results suggest that the POCA coating enhances graft biocompatibility by promoting endothelialization and reducing inflammation, thereby inhibiting neointimal hyperplasia and improving graft patency. Overall, these results highlight the therapeutic potential of an ascorbate-functionalized poly(diol-co-citrate) elastomer for vascular applications and support future evaluation in large animal models.