Producing nitric oxide by pulsed electrical discharge in air for portable inhalation therapy

Abstract

Inhalation of nitric oxide (NO) produces selective pulmonary vasodilation and is an effective therapy for treating pulmonary hypertension in adults and children. In the United States, the average cost of 5 days of inhaled NO for persistent pulmonary hypertension of the newborn is about $14,000. NO therapy involves gas cylinders and distribution, a complex delivery device, gas monitoring and calibration equipment, and a trained respiratory therapy staff. The objective of this study was to develop a lightweight, portable device to serve as a simple and economical method of producing pure NO from air for bedside or portable use. Two NO generators were designed and tested: an offline NO generator and an inline NO generator placed directly within the inspiratory line. Both generators use pulsed electrical discharges to produce therapeutic range NO (5 to 80 parts per million) at gas flow rates of 0.5 to 5 liters/min. NO was produced from air, as well as gas mixtures containing up to 90% O2 and 10% N2. Potentially toxic gases produced in the plasma, including nitrogen dioxide (NO2) and ozone (O3), were removed using a calcium hydroxide scavenger. An iridium spark electrode produced the lowest ratio of NO2/NO. In lambs with acute pulmonary hypertension, breathing electrically generated NO produced pulmonary vasodilation and reduced pulmonary arterial pressure and pulmonary vascular resistance index. In conclusion, electrical plasma NO generation produces therapeutic levels of NO from air. After scavenging to remove NO2 and O3 and filtration to remove particles, electrically produced NO can provide safe and effective treatment of pulmonary hypertension.

Electric Plasma–generated Nitric Oxide: Hemodynamic Effects in Patients with Pulmonary Hypertension

“…We previously demonstrated that NO produced by an electric plasma generator caused pulmonary vasorelaxation in lambs with pulmonary vasoconstriction induced by infusing U46619, a thromboxane analog. Both the offline and inline plasma NO generators reliably reduced the lamb's pulmonary vascular resistance (PVR) and pulmonary artery pressure (PAP) (5).…”

“…We recently developed a novel method of synthesizing NO from air or oxygen (O 2 )-rich gas mixtures by electric plasma generation (5). Two NO generators were built: an offline device, which continuously produces the gas and maintains a constant concentration of NO throughout the respiratory cycle, and an inline generator, which produces NO for 800 milliseconds beginning 20 milliseconds after the onset of inspiration.…”

Detection and removal of impurities in nitric oxide generated from air by pulsed electrical discharge

“…However, these methods produce large amounts of toxic by products, such as nitrogen dioxide (NO 2 ) and ozone (O 3 ), requiring complex purification systems [12; 13]. Recently, we designed, developed, and tested in lambs a lightweight, economic, and portable NO generation system using pulsed electrical discharge [14]. The prototype NO generation system produced a therapeutic range of NO (5–80 parts per million (ppm)) in air or an oxygen-enriched nitrogen containing gas [14].…”

“…Recently, we designed, developed, and tested in lambs a lightweight, economic, and portable NO generation system using pulsed electrical discharge [14]. The prototype NO generation system produced a therapeutic range of NO (5–80 parts per million (ppm)) in air or an oxygen-enriched nitrogen containing gas [14]. Iridium or other noble metal electrodes produced the lowest fractional amount of NO 2 /NO compared to nickel, carbon or tungsten electrodes [14].…”

“…The prototype NO generation system produced a therapeutic range of NO (5–80 parts per million (ppm)) in air or an oxygen-enriched nitrogen containing gas [14]. Iridium or other noble metal electrodes produced the lowest fractional amount of NO 2 /NO compared to nickel, carbon or tungsten electrodes [14]. Iridium is a rare and inert metal.…”