Portable Nitric Oxide (NO) Generator Based on Electrochemical Reduction of Nitrite for Potential Applications in Inhaled NO Therapy and Cardiopulmonary Bypass Surgery

Abstract

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.

Nitric oxide provides myocardial protection when added to the cardiopulmonary bypass circuit during cardiac surgery: Randomized trial

“…Moreover, new cost-effective NO generators suitable for CPB are currently under development. 29 This study has some limitations. In particular, it does not provide data regarding the optimal duration and titration dose of NO treatment as well as regarding the duration and dynamics of exposure to NO metabolites.…”

“…The cost of NO administration in the operating room during CPB surgery is less substantial compared with NO inhalation lasting for days. 29 At our institution, estimated cost of 40-ppm NO treatment was $70. In literature, the reported cost of the NO is $6/L.…”

Inhaled nitric oxide

“…to 500 p.p.m. (Qin et al ., 2017). However, the instability of the mediators and the short lifespan of the copper‐complex covered electrodes (currently less than 48 h) suggest that this approach requires further investigation and improvement.…”

Inhaled Pulmonary Vasodilators in the Neonatal and Pediatric ICU

“…In addition to the nitric oxide generators in the previous section about new INO delivery devices, there are a few additional experimental nitric oxide generators showing promise. Qin et al 101 presented a portable nitric oxide generator that produces nitric oxide at the surface of a large mesh of working electrodes by electrochemical reduction of the nitrite ion in the presence of a soluble copper (II)ligand electron transfer mediator complex. Nitric oxide generated with this system is transported by purging with a nitrogen and air combination.…”