A Proof Of Concept Study Of Human Volunteers And Pulmonary Hypertension Patients Breathing Nitric Oxide Produced By Electrical Pulsed Discharge

RATIONALE Administration of nitric oxide (NO) gas by inhalation produces localized smooth muscle relaxation of the pulmonary vasculature without dilating the systemic vasculature. Although inhaled NO is widely used to treat pulmonary hypertension in acute settings the complexity and weight of cylinder delivery systems and high costs have limited its use to tertiary hospitals in economically developed countries. We recently reported a novel lightweight device that generates NO, either intermittently or continuously, from air by means of electrical pulsed discharge (1). In this study, we examined the short-term safety of NO delivery via this device to both healthy adult volunteers and patients with pulmonary hypertension (PH). In the PH group, we also compared the hemodynamic responses between electrically produced NO and conventional gas cylinder NO. METHODS HEALTHY-study: Six healthy-adult volunteers breathed 25ppm NO produced by electrical discharge for 10 minutes each from two NO generators: continuous NO producing generator, and intermittent, inline NO generator, triggered during early inspiration. We recorded vital signs, methemoglobin (MetHb) and venous cGMP levels, and plasma nitrate at baseline and after 10 minutes of breathing NO from each of the two-generation systems. CATH-study: Six adult-patients with precapillary pulmonary hypertension who were acutely responsive to conventional gas tank NO inhalation (defined for this study as a pulmonary vascular resistance index (PVR), decrease of ≥20% from baseline) were enrolled. Pulmonary and systemic hemodynamics were recorded before and after gas cylinder NO, and each of the two electrically generated NO systems. RESULTS Six healthy volunteers (HEALTHY-study) and, to date, two patients (CATH-study) have completed the study. The maximum NO dose delivered was 25ppm and nitrogen dioxide 0.1ppm. No adverse events were noted and methemoglobin remained always below 1.2%. Hemodynamic data and main results are summarized in the table. CONCLUSIONS Inhaled NO, produced electrically from air, appears, in preliminary tests, to be safe and, compared to NO delivered by gas cylinder, produce equivalent acute hemodynamic effects. Reference: Yu et al. Sci Transl Med. 2015;7(294):294ra107.