INHIBITION OF STENOSIS AT THE GRAFT/VEIN ANASTOMOSIS

抑制移植物/静脉吻合处的狭窄

• 批准号: 6211104
• 负责人: STEPHEN N BUNKER
• 金额: $ 10万
• 依托单位: IMPLANT SCIENCES CORPORATION
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-30 至 2003-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6211104
• 关键词: artery stenosis; biomaterial development /preparation; biomedical equipment development; chronic renal failure; dogs; drug administration rate /duration; drug delivery systems; histology; implant; ionizing radiation; physiologic anastomosis; radiation therapy; radiation therapy dosage

End-stage renal disease (ESRD) was inevitably fatal until the development of an external shunt together with the use of dialysis technology. According to the NIH, the incidence of treated ESRD in the US is rising 7.8% per year. Over 200,000 ESRD patients are presently being treated with hemodialysis through a graft/vein shunt. Current experience has shown that these grafts typically fall in 14-19 months. Clinically, most graft failures are secondary to thrombosis resulting from stenosis at the graft/vein anastomosis. Stenosis is the result of a cellular proliferation similar to that observed following other vascular interventions, including angioplasty and synthetic bypass graft placement. Similar intimal hyperplasia responses to vascular interventions (e.g. angioplasty) have been recently treated with ionizing radiation. Nearly all of the methods thus far proposed treat arterial vessels from the inside. Stenotic lesions are frequently eccentric within the vessel lumen, and proliferation is believed to be initiated in the smooth muscle cells near the adventitial layer of the vessel. It is proposed that an optimum prophylactic treatment for the threatened stenosis would deliver therapeutic levels of ionizing radiation over an extended period of time via a device that is positioned around the vessel/graft junction at the time of graft implant surgery. An external "wrap-around" source of radiation provides far greater spatial uniformity of dose in the treatment zone than an internal source. The selection of backing is important for minimizing dose to other tissue and to the physician. Only a single procedure is required to install both the graft and the wrap. PROPOSED COMMERCIAL APPLICATIONS: End-stage renal disease is treated with dialysis technology using an external shunt for access. The shunt graft frequently fails within a year due to low blood flow caused by stenosis. This proposal describes a method for inhibiting stenosis, significantly reducing revision surgeries and trauma to the patient.

终末期肾病（ESRD）是不可避免的致命的，直到开发的外部分流与透析技术的使用。根据美国国立卫生研究院的数据，美国接受治疗的ESRD的发病率每年上升7.8%。目前有超过200，000名ESRD患者正在通过移植物/静脉分流进行血液透析治疗。目前的经验表明，这些移植物通常在14-19个月内脱落。临床上，大多数移植物失败是继发于移植物/静脉吻合处狭窄导致的血栓形成。狭窄是细胞增殖的结果，类似于在其他血管干预（包括血管成形术和合成旁路移植物放置）后观察到的结果。血管介入（如血管成形术）引起的类似内膜增生反应最近已被电离辐射治疗。迄今为止提出的几乎所有方法都是从内部治疗动脉血管。狭窄病变在血管腔内经常是偏心的，并且增殖被认为是在血管外膜层附近的平滑肌细胞中开始的。建议对威胁性狭窄的最佳预防性治疗将在移植物植入手术时通过位于血管/移植物接合处周围的器械在较长时间内输送治疗水平的电离辐射。外部“环绕”辐射源在治疗区中提供比内部源大得多的剂量空间均匀性。背衬的选择对于最小化对其他组织和医生的剂量很重要。仅需要一个程序来安装移植物和包裹物。拟定的商业应用：使用外部分流器进行通路的透析技术治疗终末期肾病。由于狭窄引起的低血流量，分流移植物经常在一年内失效。该提案描述了一种抑制狭窄、显著减少翻修手术和患者创伤的方法。