New England Society for Vascular Surgery
August 11, 2005

Inhibition Of Intimal Hyperplasia In ePTFE Covered Stents Using Recombinant Human Thrombomodulin (rTM)

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Geoffrey Wong, Jian-ming Li, Mohammad H. Eslami, Michael J. Rohrer, Bruce S. Cutler
University of Massachusetts Medical School, Worcester, MA

Objectives:
We sought to evaluate the ability of a recombinant human thrombomodulin (rTM) to inhibit neointimal hyperplasia (IH) in ePTFE covered stents in a porcine carotid artery model of arterial injury.
Methods:
Five standard ePTFE covered Viabahn stents (W.L. Gore, Tempe, AZ) and seven rTM-covered Viabahn stents were inserted into porcine left distal common carotid arteries (CCAs) utilizing an endovascular approach. Two weeks prior to stent deployment, the left CCA of each animal had been balloon injured to stimulate neointimal hyperplasia. Carotid angiograms were obtained at the time of balloon injury, two weeks following balloon injury, and four weeks after stent placement to assess the degree of luminal stenosis. One month after stent graft implantation the stent grafts were extracted after in situ perfusion fixation was performed. They were then cross-sectioned into proximal, middle and distal segments and luminal area measurements were calculated using computerized planimetry analysis.
Results:
In the control group, one of the five stent grafts was noted to be thrombosed at the time of explantation. Stent patency was observed in all five of the explanted rTM-coated stents, while two remain in vivo. Mean luminal diameter of the rTM-coated stents at explantation was 93 ± 1.9% of the original arterial diameter compared to 67 ± 29% in the control group (p=0.05). Histomorphologic analysis demonstrated the area obliterated by IH at the proximal portion of the rTM-stent was reduced compared to control group (3.05 ± 0.40mm2 vs. 4.44 ± 0.35mm2, p=0.04).
Conclusions:
Neointimal hyperplasia is inhibited in PTFE covered stents treated with rTM compared to untreated stent grafts, as documented by improved luminal diameter noted on angiography and cross-sectional histologic evaluation. These findings suggest that treatment of PTFE with recombinant human thrombomodulin may improve long-term prosthetic graft patency.

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