Inhibition of vein graft intimal and medial thickening by periadventitial application of a sulfated carbohydrate polymer

Purpose: The purpose of this study was to determine whether the wall thickening observed in vein grafts after they were placed into the arterial circulation could be inhibited by periadventitial delivery of an insoluble sulfated polymer of β-cyclodextrin (P-CDS) capable of tightly binding heparin binding growth factors. Methods: Thirty-four New Zealand white rabbits underwent implantation of reversed autologous jugular vein interposition grafts in the common carotid artery and were randomized to receive either 20 mg P-CDS (n = 18) topically around the graft or no additional therapy (n = 16). Before being killed at 28 days, animals were given bromodeoxyuridine to assess smooth muscle cell proliferation. Histomorphometric analyses were performed after perfusion fixation. Results: Compared to controls, treatment with P-CDS was associated with reduced mean intimal thickness (24±3 vs 38±4 μm; mean±SEM, p< 0.01) and intimal area (0.25 ± 0.03 vs 0.54 ± 0.09 mm²; p < 0.01). There was also significantly less medial thickness in the P-CDS group (45 ± 3 vs 63 ± 3, p < 0.001). There was no significant difference in intimal or medial smooth muscle cell proliferation between P-CDS-treated and control vein grafts at 28 days. The polymer persisted in the adventitia with a mild foreign body reaction. Conclusion: Periadventitial placement of P-CDS, a novel, insoluble, sulfated carbohydrate polymer, inhibits intimal and medial thickening of vein bypass grafts in this model of vein grafting. The persistence of P-CDS in vivo for prolonged periods, and the ease of topical application of P-CDS during vascular bypasses may have important implications for its future use in vascular surgery.