Inhibition of vein graft intimal and medial thickening by periadventitial application of a sulfated carbohydrate polymer.
Inhibition of vein graft intimal and medial thickening by periadventitial application of a sulfated carbohydrate polymer.
复制标题
通过外膜周围应用硫酸化碳水化合物聚合物来抑制静脉移植物内膜和内侧增厚。
DOI：
10.1016/s0741-5214(96)80046-2
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发表时间：
1996
影响因子：
4.3
通讯作者：
Golden,MA
中科院分区：
文献类型：
--
作者：
Toes,GJ;Barnathan,ES;Liu,H;Raghunath,PN;Tomaszewski,JE;Caron,RJ;Weisz,PB;vanOeveren,W;Golden,MA
目的本研究的目的是确定静脉移植物进入动脉循环后观察到的壁增厚是否可以通过皮下递送一种能紧密结合肝素结合生长因子的不溶性硫酸化聚合物β-环糊精（P-CDS）来抑制。方法34只新西兰大白兔在颈总动脉内植入逆行自体颈静脉间置移植物，随机分为两组，一组在移植物周围局部接受20 mg P-CDS (n=18)，另一组不接受其他治疗（n=16）。28天处死前，给药溴脱氧尿苷，观察平滑肌细胞增殖情况。灌注固定后进行组织形态学分析。结果与对照组相比，p - cds治疗与平均内膜厚度（24±3 vs 38±4 μm，平均±SEM， p<0.01）和内膜面积（0.25±0.03 vs 0.54±0.09 mm2, p<0.01）相关。p - cds组的内侧厚度也明显减少（45±3比63±3，p<0.001）。第28天，p - cds处理与对照静脉移植物的内膜或内侧平滑肌细胞增殖无显著差异。聚合物在外膜中持续存在，伴有轻微的异物反应。结论P-CDS是一种新型的不溶性硫酸碳水化合物聚合物，可抑制静脉旁路移植血管内膜和内侧增厚。P-CDS在体内长时间的持续存在，以及在血管分流术中局部应用P-CDS的便性，可能对其未来在血管手术中的应用具有重要意义。
PurposeThe 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.MethodsThirty-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.ResultsCompared 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.ConclusionPeriadventitial 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.