Reducing Tunneled Dialysis Catheter Dysfunction through Nitric Oxide Release

通过释放一氧化氮减少隧道式透析导管功能障碍

• 批准号: 8638515
• 负责人: MARK E MEYERHOFF
• 金额: $ 25.53万
• 依托单位: UNIVERSITY OF CINCINNATI
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-30 至 2015-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8638515
• 关键词: Address; Adherence; Animals; Anti-Bacterial Agents; Arteriovenous fistula; Biocompatible Materials; Biological; Blood; Blood Platelets; Blood Vessels; Catheters; Cell Proliferation; Central Vein; Clinical; Copper; Development; Dialysis patients; Dialysis procedure; Electrodes; Family suidae; Fibrin; Figs - dietary; Fistula; Functional disorder; Geographic Distribution; Hemodialysis; Hour; Hyperplasia; Infection; Ions; Measures; Mediator of activation protein; Microbial Biofilms; Modeling; Morbidity - disease rate; Nitric Oxide; Nitric Oxide Pathway; Nitrites; Oxides; Pathway interactions; Patients; Plague; Platelet aggregation; Polymers; Polytetrafluoroethylene; Population; Prevalence; Series; Smooth Muscle; Smooth Muscle Myocytes; Solutions; Stenosis; System; Technology; Testing; Thrombosis; Thrombus; Time; United States; Validation; Venous; Venous system; cost; economic cost; effective therapy; fluorophore; in vivo; innovative technologies; mortality; new technology; novel; public health relevance; seal; voltage

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.

总结 隧道透析导管（TDC）是透析血管通路的重要模式。80%的事故 透析患者开始血液透析时具有TDC，并且在美国的总体流行率约为25%。 不幸的是，TDC存在感染、血栓形成和中心静脉狭窄的巨大问题，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，具有较强的抗菌、抗血小板聚集等作用 和抗平滑肌细胞增殖活性，这可能潜在地减少TDC并发症。我们有 先前开发了一种新颖的创新技术，以电化学方式调节NO释放（在 导管内腔）;其中嵌入亚硝酸盐溶液中的铜电极能够产生NO（通过 Cu离子和亚硝酸盐之间的相互作用）。 该建议的中心假设是，从管腔中电化学调节的NO释放 在TDC内可以针对与TDC使用相关的所有三种主要并发症（感染、血栓形成和 中心静脉狭窄）;从而显著降低了巨大的发病率、死亡率和相关的经济成本 使用TDC。 我们计划通过一系列具体目标来解决这一中心假设，这些目标侧重于： 和具有生物活性的电化学调制的NO释放系统的验证（在TDC管腔内）。 活性（B）在猪体内用释放NO的TDC减少感染、血栓形成和中心静脉狭窄 模型 我们相信，对于减少TDC功能障碍和感觉障碍的新疗法，存在巨大的未满足的临床需求。 释放NO的TDC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。