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 t hickening observed in vein grafts after they were placed into the arte rial circulation could be inhibited by periadventitial delivery of an insoluble sulfated polymer of beta-cyclodextrin (P-CDS) capable of tig htly binding heparin binding growth factors. Methods: Thirty-four New Zealand white rabbits underwent implantation of reversed autologous ju gular 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 da ys, animals were given bromodeoxyuridine to assess smooth muscle cell proliferation. Histomorphometric analyses were performed after perfusi on fixation. Results: Compared to controls, treatment with P-CDS was a ssociated with reduced mean intimal thickness (24 +/- 3 vs 38 +/- 4 mu m; mean +/- SEM, p < 0.01) and intimal area (0.25 +/- 0.03 vs 0.54 +/ - 0.09 mm(2); P < 0.01). There was also significantly less medial thic kness 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 prol iferation between P-CDS-treated and control vein grafts at 28 days. Th e polymer persisted in the adventitia with a mild foreign body reactio n. 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 appli cation of P-CDS during vascular bypasses may have important implicatio ns for its future use in vascular surgery.