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.

 说明(申请人提供)：吸入型一氧化氮(INO)在医院内被广泛用于治疗肺衰竭，从成人的急性呼吸窘迫综合征(ARDS)和新生儿的持续性肺动脉高压(PPHN)，到先天性心脏病和肺炎或其他肺部感染患者的术后肺动脉高压。NO产生不足的门诊患者，包括囊性纤维化和慢性鼻窦炎患者，INO可能也有很大益处，在这些患者中，NO水平不足与上呼吸道上皮细胞慢性感染/生物膜形成的高风险有关。此外，在体外循环(EC)程序(包括体外循环(CPB)和体外膜氧合(ECMO))中使用的氧合器中添加气相NO也可能有助于防止血小板(导致血栓)和白细胞(导致全身炎症反应综合征(SIRS))的激活。由于压缩气瓶通常含有100-400ppmv(氮气中)的NO，目前用于生物医学应用的产生治疗水平的气相NO的方法非常昂贵。事实上，随着时间的推移，这种水平的NO可以发生不成比例的反应，产生低水平的有毒NO2。因此，需要不断监测这些物种的气相浓度，并强制使用相对较新的NO压缩罐，从而使INO和EC应用气相并不是非常昂贵。为了大大降低成本，并潜在地增加治疗性气相NO的更广泛用途(可能也用于家庭用途)，我们现在提出了一种简单的电化学NO发生器，它可以从溶解的无机亚硝酸盐(NO2-)的小储存液中按需生产纯NO气体。使用新型铜(II)配体络合物作为电子转移媒介，在大面积网状电极上通过单电子电化学还原NO2-生成NO气体。以这种方式产生的NO气体水平将通过气体交换器中空纤维扩散，在流动的氮气气流中产生所需的NO水平，然后在下游用氧气/空气适当稀释，以用于潜在的INO以及EC扫气应用。通过这项R21资助，我们将优化这种方法的化学/电化学，通过红外光谱检查气相中产生的NO的纯度，并展示仅通过改变电化学还原反应的施加电压/电流来控制源和接受气流中精确的NO水平的能力。我们亦会研究以下项目的可行性： 采用高灵敏度的NO气相传感器，连续监测由这项新技术产生的气相中的NO水平，以伺服调节亚硝酸盐/铜(II)-配位体复杂油藏溶液中的电化学NO生成过程。