Lin Peter H, Chen Changyi, Bush Ruth L, Yao Qizhi, Lumsden Alan B, Hanson Stephen R
Division of Vascular Surgery & Endovascular Therapy, DeBakey Department of Surgery, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
J Vasc Surg. 2004 Jun;39(6):1322-8. doi: 10.1016/j.jvs.2004.01.046.
Intimal hyperplasia and graft thrombosis are major causes of graft failure. Heparin prolongs graft patency and inhibits neointimal hyperplasia in animal models. The purpose of this study was to evaluate the effect of a heparin-coated expanded polytetrafluoroethylene (ePTFE) graft on platelet deposition and anastomotic neointimal hyperplasia after aortoiliac bypass grafting in a baboon model.
Heparin-coated ePTFE grafts (4-mm diameter) were incorporated into exteriorized femoral arteriovenous shunts placed in five baboons. Platelet deposition was analyzed by measuring the accumulation of indium 111-labeled platelets on the grafts, with dynamic scintillation camera imaging. Eight adult male baboons (mean weight, 9.3 kg) underwent bilateral aortoiliac bypass grafting with ePTFE grafts (4-mm internal diameter). In each animal a heparin-coated ePTFE graft was placed in one aortoiliac artery, and an uncoated graft, which served as the control, was placed in the contralateral aortoiliac artery. All grafts were harvested at 4 weeks, and were analyzed quantitatively for neointimal hyperplasia at graft-vessel anastomoses.
Early platelet deposition on heparin-coated grafts after 1 to 4 hours of ex vivo circuitry was significantly reduced. All the harvested aortoiliac grafts were patent at 4 weeks. There was a significant reduction in neointimal area at both proximal (0.26 +/- 0.11 mm(2)) and distal (0.29 +/- 0.14 mm(2)) anastomoses in the heparin-coated grafts, compared with proximal (0.56 +/- 0.18 mm(2)) and distal (0.63 +/- 0.21 mm(2)) anastomoses in the untreated control grafts (P <.05). In addition, neointimal cell proliferation assayed with bromodeoxyuridine (BrdU) incorporation was reduced in the graft neointima (3.47% +/- 0.43%) in heparin-coated grafts compared with the graft neointima (6.21% +/- 0.59%) in untreated control grafts (P <.05).
Small-caliber heparin-coated ePTFE grafts significantly reduce platelet deposition and anastomotic neointimal hyperplasia and cell proliferation, without measurable side effects, in baboons. Surface coating with heparin in small-caliber ePTFE grafts is useful for improving prosthetic bypass graft patency.
An autologous vein graft is the ideal bypass conduit in peripheral arterial reconstruction; however, many patients who undergo bypass grafting do not have adequate or available autologous vein graft. As a result surgeons often must rely on prosthetic grafts as an alternative conduit in arterial bypass procedures. Clinical outcomes with prosthetic grafts in peripheral arterial reconstruction are generally inferior to those with autologous vein bypass grafts, in part because of anastomotic neointimal hyperplasia. This study evaluated the effect of small-caliber heparin-coated expandable polytetrafluoroethylene (ePTFE) grafts in aortoiliac reconstruction in a baboon model. The study found that heparin-coated ePTFE grafts resulted in less intimal hyperplasia and less platelet deposition after implantation, compared with noncoated control ePTFE grafts.
内膜增生和移植物血栓形成是移植物失败的主要原因。在动物模型中,肝素可延长移植物通畅时间并抑制内膜增生。本研究的目的是评估肝素涂层的膨体聚四氟乙烯(ePTFE)移植物在狒狒模型中进行主髂动脉搭桥术后对血小板沉积和吻合口内膜增生的影响。
将肝素涂层的ePTFE移植物(直径4mm)植入置于5只狒狒体内的体外股动静脉分流管中。通过动态闪烁相机成像,测量铟111标记的血小板在移植物上的聚集情况,分析血小板沉积。8只成年雄性狒狒(平均体重9.3kg)接受了双侧主髂动脉搭桥术,使用ePTFE移植物(内径4mm)。在每只动物的一侧主髂动脉中植入肝素涂层的ePTFE移植物,在对侧主髂动脉中植入未涂层的移植物作为对照。所有移植物在4周时取出,对移植物与血管吻合处的内膜增生进行定量分析。
体外循环1至4小时后,肝素涂层移植物上的早期血小板沉积显著减少。所有取出的主髂动脉移植物在4周时均保持通畅。与未处理的对照移植物近端(0.56±0.18mm²)和远端(0.63±0.21mm²)吻合处相比,肝素涂层移植物近端(0.26±0.11mm²)和远端(0.29±0.14mm²)吻合处的内膜面积显著减少(P<.05)。此外,与未处理的对照移植物的移植物内膜(6.21%±0.59%)相比,肝素涂层移植物的移植物内膜中用溴脱氧尿苷(BrdU)掺入法测定的内膜细胞增殖减少(3.47%±0.43%)(P<.05)。
在狒狒中,小口径肝素涂层的ePTFE移植物可显著减少血小板沉积、吻合口内膜增生和细胞增殖,且无明显副作用。小口径ePTFE移植物表面涂覆肝素有助于提高人工搭桥移植物的通畅率。
自体静脉移植物是外周动脉重建的理想搭桥管道;然而,许多接受搭桥手术的患者没有足够的或可用的自体静脉移植物。因此,外科医生在动脉搭桥手术中常常必须依靠人工移植物作为替代管道。人工移植物在外周动脉重建中的临床效果通常不如自体静脉搭桥移植物,部分原因是吻合口内膜增生。本研究评估了小口径肝素涂层的可扩张聚四氟乙烯(ePTFE)移植物在狒狒模型主髂动脉重建中的效果。研究发现,与未涂层的对照ePTFE移植物相比,肝素涂层的ePTFE移植物植入后内膜增生较少,血小板沉积也较少。