Reducing Tunneled Dialysis Catheter Dysfunction through Nitric Oxide Release

摘要 隧道式透析导管是一种重要的透析血管通路。80%的事故 透析患者开始使用TDC进行血液透析，美国的总体患病率约为25%。 不幸的是，tdcs在感染、血栓形成和中心静脉狭窄方面存在巨大问题，这导致 在发病率、死亡率和经济成本上都非常显著。尽管临床问题很严重， 然而，对于TDC功能障碍，目前还没有有效的治疗方法。 一氧化氮(NO)是一种重要的生物介质，具有很强的抗细菌、抗血小板聚集作用。 和抗平滑肌细胞增殖活性，这可能会潜在地减少TDC并发症。我们有 之前开发了一种新颖的创新技术，以电化学方式调节NO的释放(在 导管管腔)；其中嵌入亚硝酸盐溶液中的铜电极能够产生NO(通过 铜离子和亚硝酸盐之间的相互作用)。 这一提议的中心假设是，电化学调制的NO从管腔释放 在TDC内可以针对与使用TDC相关的所有三个主要并发症(感染、血栓和 中心静脉狭窄)；从而显著降低相关的巨大发病率、死亡率和经济成本 使用贸发局。 我们计划通过一系列具体目标来解决这一中心假设，这些目标集中在(A)发展 以及(在TDC管腔内)电化学调制的NO释放系统与生物的验证 活性(B)通过体内NO释放tDCs减少感染、血栓形成和中心静脉狭窄 模特。 我们相信，对于减少TDC功能障碍和感觉的新疗法有着巨大的临床需求，尚未得到满足。 NO释放tdcs的概念可以显著降低巨大的临床发病率和经济成本。 与这个棘手的问题有关。

SUMMARY Tunneled Dialysis Catheters (TDCs) are an important mode of dialysis vascular access. 80% of incident dialysis patients begin hemodialysis with a TDC and the overall prevalence in the US is approximately 25%. Unfortunately, TDCs have huge problems with infection, thrombosis and central venous stenosis, which results in a very significant morbidity, mortality and economic cost. Despite the magnitude of the clinical problem, however, there are no effective therapies for TDC dysfunction. Nitric oxide (NO) is an important biological mediator, which has potent anti-bacterial, anti-platelet aggregation and anti-smooth muscle cell proliferation activities, which could potentially reduce TDC complications. We have previously developed a novel and innovative technology, to electrochemically modulate NO release (within a catheter lumen); in which a copper electrode embedded in a nitrite solution is able to generate NO (through the interaction between Cu ions and nitrite) over a prolonged period of time. The central hypothesis of this proposal, is that the electrochemically modulated release of NO from a lumen within a TDC could target all three major complications associated with TDC use (infection, thrombosis and central vein stenosis); thus significantly reducing the huge morbidity, mortality and economic cost associated with TDC use. We plan to address this central hypothesis through a series of specific aims that focus on (a) the development and validation (within a TDC lumen) of an electrochemically modulated NO release system with biological activity (b) reducing infection, thrombosis and central vein stenosis with NO releasing TDCs in-vivo, in a pig model. We believe that there is a huge unmet clinical need for novel therapies that reduce TDC dysfunction and feel that the concept of NO releasing TDCs could significantly reduce the huge clinical morbidity and economic cost associated with this intractable problem.