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: 8741962
• 负责人: MARK E MEYERHOFF
• 金额: $ 11.83万
• 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 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8741962
• 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

DESCRIPTION (provided by applicant): 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.

描述（由申请人提供）：隧道透析导管（TDC）是透析血管通道的重要方式。 80％的事件透析患者开始使用TDC开始血液透析，美国的总体患病率约为25％。不幸的是，TDC在感染，血栓形成和中央静脉狭窄方面存在巨大问题，这导致了非常明显的发病率，死亡率和经济成本。尽管存在临床问题的幅度，但是尚无有效的TDC功能障碍疗法。一氧化氮（NO）是一个重要的生物介体，具有有效的抗细菌，抗血小板聚集和抗滑动的肌肉细胞增殖活性，这可能有可能减少TDC并发症。我们以前已经开发了一种新颖而创新的技术，可以在电化学上调节无释放（在导管管腔内）；其中嵌入亚硝酸盐溶液中的铜电极能够在延长的时间内生成NO（通过Cu离子和亚硝酸盐之间的相互作用）。该提案的中心假设是，从TDC内的管腔中的NO的电化学调制释放可以针对与TDC使用相关的所有三种主要并发症（感染，血栓形成和中央静脉狭窄）；因此，大大降低了与TDC使用相关的巨大发病率，死亡率和经济成本。我们计划通过一系列特定目标来解决这一中心假设，该目标集中在（a）具有生物学活性的电化学调节的无释放系统（b）减少感染，血栓形成和中央静脉狭窄的发育和验证（在TDC腔内），没有释放出猪内的TDC。我们认为，对新型疗法有巨大的未满足的临床需求，可减少TDC功能障碍，并认为没有释放TDC的概念可以显着降低与此棘手问题相关的巨大临床发病率和经济成本。