Department of Chemistry and ‡Department of Surgery, University of Michigan , Ann Arbor, Michigan 48109, United States.
Mol Pharm. 2017 Nov 6;14(11):3762-3771. doi: 10.1021/acs.molpharmaceut.7b00514. Epub 2017 Oct 25.
A new portable gas phase nitric oxide (NO) generator is described for potential applications in inhaled NO (INO) therapy and during cardiopulmonary bypass (CPB) surgery. In this system, NO is produced at the surface of a large-area mesh working electrode by electrochemical reduction of nitrite ions in the presence of a soluble copper(II)-ligand electron transfer mediator complex. The NO generated is then transported into gas phase by either direct purging with nitrogen/air or via circulating the electrolyte/nitrite solution through a gas extraction silicone fiber-based membrane-dialyzer assembly. Gas phase NO concentrations can be tuned in the range of 5-1000 ppm (parts per million by volume for gaseous species), in proportion to a constant cathodic current applied between the working and counter electrodes. This new NO generation process has the advantages of rapid production times (5 min to steady-state), high Faraday NO production efficiency (ca. 93%), excellent stability, and very low cost when using air as the carrier gas for NO (in the membrane dialyzer configuration), enabling the development of potentially portable INO devices. In this initial work, the new system is examined for the effectiveness of gaseous NO to reduce the systemic inflammatory response (SIR) during CPB, where 500 ppm of NO added to the sweep gas of the oxygenator or to the cardiotomy suction air in a CPB system is shown to prevent activation of white blood cells (granulocytes and monocytes) during extracorporeal circulation with cardiotomy suction conducted with five pigs.
一种新型便携式气相一氧化氮(NO)发生器,可用于吸入式一氧化氮(INO)治疗和体外循环(CPB)手术期间。在该系统中,通过在可溶性铜(II)-配体电子转移介体络合物存在下电化学还原亚硝酸盐离子,在大面积网状工作电极表面产生 NO。然后通过用氮气/空气直接吹扫或通过将电解质/亚硝酸盐溶液循环通过基于硅酮纤维的气体提取膜-透析器组件,将产生的 NO 输送到气相中。气相中 NO 浓度可以在 5-1000ppm(体积比为气态物质)范围内进行调节,与在工作电极和对电极之间施加的恒定阴极电流成比例。当使用空气作为 NO 的载气(在膜透析器配置中)时,这种新的 NO 产生过程具有快速生产时间(5 分钟达到稳定状态)、高法拉第 NO 生产效率(约 93%)、极好的稳定性和非常低的成本,从而可以开发潜在的便携式 INO 设备。在这项初步工作中,研究了该新型系统在 CPB 期间通过添加气态 NO 来减轻全身炎症反应(SIR)的效果,结果表明,在 CPB 系统中,将 500ppm 的 NO 添加到氧气机的吹扫气体中或添加到心内吸引空气中,可防止在体外循环期间激活白细胞(粒细胞和单核细胞)心内吸引采用五只猪进行。