Electrochemical Generation of Nitric Oxide for Gas Phase Biomedical Applications

用于气相生物医学应用的电化学生成一氧化氮

• 批准号: 9243306
• 负责人: Robert H. Bartlett
• 金额: $ 18.75万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-04-01 至 2019-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9243306
• 关键词: Adult; Adult Respiratory Distress Syndrome; Aerosols; Air; Area; Blood; Breathing; Bypass; Cardiopulmonary Bypass; Catheters; Cathodes; Chemistry; Chronic; Clinical; Coagulation Process; Complex; Copper; Cystic Fibrosis; Diffuse; Electrochemistry; Electrodes; Electron Transport; Electrons; Engineering; Epithelial Cells; Extracorporeal Circulation; Extracorporeal Membrane Oxygenation; Failure; Feedback; Fiber; Gases; Generations; Goals; Grant; Home environment; Hospitals; Infection; Intensive Care; Investigation; Ions; Laboratories; Legal patent; Leukocytes; Ligands; Link; Local Anti-Infective Agents; Lung; Lung Transplantation; Measures; Mediator of activation protein; Medical; Medicine; Membrane; Methods; Michigan; Microbial Biofilms; Monitor; Neonatology; Newborn Infant; Nitric Oxide; Nitrites; Nitrogen; Nitrogen Dioxide; Oxygen; Oxygenators; Patients; Phase; Platelet Activation; Platinum; Pneumonia; Postoperative Period; Preparation; Procedures; Process; Production; Pulmonary Hypertension; Reaction; Regulation; Reporting; Research Proposals; Sepsis Syndrome; Side; Sodium Chloride; Source; Spectrum Analysis; Stainless Steel; Stream; Surface; System; Techniques; Technology; Therapeutic; Therapeutic Uses; Thrombus; Time; Universities; chronic rhinosinusitis; clinical application; congenital heart disorder; cost; design; high risk; inhaled nitric oxide; interest; new technology; novel; persistent pulmonary hypertension; portability; prevent; public health relevance; purge; respiratory gas; sensor; tuberculosis treatment; voltage

 DESCRIPTION (provided by applicant): Inhaled nitric oxide (INO) is widely used within hospitals to treat lung failure, ranging from acute respiratory distress syndrome (ARDS) in adults and persistent pulmonary hypertension in newborns (PPHN), to postoperative pulmonary hypertension in patients with congenital heart disease and patients with pneumonia or other lung infections. INO may also have great benefit to ambulatory patients deficient in NO production, including those with cystic fibrosis and chronic rhinosinusitis, in which inadequate levels of NO are linked to high risks of chronic infection/biofilm formation on epithelial cells tht line the upper airways. Further, addition of gas phase NO to the sweep gas used in oxygenators that are employed in extracorporeal circulation (EC) procedures (including cardio-pulomonary bypass (CPB) and extracorporeal membrane oxygenation (ECMO)) can also potentially be useful in preventing activation of platelets (leading to thrombus) and leukocytes (leading to systemic inflammatory response syndrome (SIRS)). Current methods to generate therapeutic levels of gas phase NO for biomedical applications are very expensive, owing to the high cost of compressed gas cylinders typically containing 100 - 400 ppmv of NO (in nitrogen). Indeed, with time, NO at such levels can undergo disproportionation reactions to generate low levels of toxic NO2. Hence, constant monitoring of the gas phase concentrations of these species is required, and use of relatively new compressed tanks of NO are mandatory, making INO and EC applications of gas phase NO extremely expensive. To greatly reduce the cost, and potentially increase the broader use of therapeutic gas phase NO (possibly also for home use), we now propose a simple electrochemical NO generator that makes pure NO gas on demand from a small reservoir solution of dissolved inorganic nitrite (NO2-) salt. The NO gas will be generated by a one electron electrochemical reduction of NO2- at large area mesh electrodes using novel copper(II)-ligand complexes that serve as electron transfer mediators. The NO gas levels produced in this manner will diffuse through gas exchanger hollow fibers to create the desired NO levels within a flowing nitrogen stream that will then be appropriately diluted downstream with oxygen/air for potential INO as well as EC sweep gas applications. Via this R21 grant, we will optimize the chemistry/electrochemistry for this approach, examine the purity of NO produced in the gas phase via IR spectroscopy and demonstrate the ability to control the precise NO levels in the source and recipient gas streams merely by varying the applied voltage/current for the electrochemical reduction reaction. We will also examine the feasibility of incorporating a highly sensitive NO gas phase sensor to continuously monitor NO levels within the gas phases produced by this new technology to servo-regulate the electrochemical NO generation process in the nitrite/Cu(II)-ligand complex reservoir solution.

 描述（适用提供）：吸入的一氧化氮（INO）被广泛用于治疗肺部衰竭，从成年人的急性呼吸遇险综合征（ARD）和新生儿（PPHN）的持续性肺动脉高压（PPHN）（PPHN）持续，到患有良性心脏病患者的肺部高血压或其他PNEMONIA或其他Pneumon。 INO也可能对缺乏无生产的卧床患者有很大的好处，包括患有囊性纤维化和慢性鼻孔炎的患者，其中NO水平不足与上皮细胞上慢性感染/生物膜形成的高风险有关。此外，在体外循环（EC）程序（包括心脏 - 脉促旁路（CPB）（CPB）和体体膜氧合（ECMO）中使用的氧合剂中使用的扫描气体NO的添加可能也可能在于预防血小板激活（导致大型综合症）（导致SERMANS综合症）（导致综合症状），也可能有用。当前的生物医学应用气相NO的治疗水平的方法非常昂贵，这是因为压缩气缸的高成本通常包含100-400 ppmv no（氮）。实际上，随着时间的流逝，这种水平没有任何级别的反应会产生低水平的有毒NO2。因此，需要对这些物种的气相浓度进行持续监测，并且使用相对较新的压缩箱的使用是强制性的，使气相的INO和EC应用并不昂贵。为了大大降低成本，并有可能增加对热气相NO的更广泛使用（可能也用于家庭使用），我们现在提出了一个简单的电化学无发电机，该发电机可从溶解的无机亚硝酸盐（NO2-）盐的小型溶液溶液中纯净无气。通过使用新型铜（II）配合物作为电子传递介质的新型铜（II）配合物，在大面积网状电极上将NO2的一个电子电化学还原产生，将产生无气体。以这种方式产生的无气水平将通过气体交换器空心纤维扩散，以在流动的氮流中创建所需的无水平，然后将其在氧气/空气下向下游稀释，以获得潜在的INO以及EC清除气体应用。通过此R21赠款，我们将通过IR光谱检查在气相中检查气相中的NO的纯度，并证明能够控制源和受体气体中的精确NO水平，仅通过改变电化学还原减少反应的施加电压/电流，可以优化化学/电化学的纯度。我们还将检查 结合了高度敏感的无气相传感器，以在这项新技术生成的气相中连续监测无水平，以伺服调节亚硝酸盐/Cu（II） - 配体配合储层溶液中的电化学无生成过程。