title: Use of ultra pure nitric oxide generated by the reduction of nitrogen dioxide to reverse pulmonary hypertension in hypoxemic swine.
abstract: Inhaled nitric oxide (NO) has the capacity to selectively dilate pulmonary blood vessels, and thus enhance the matching of ventilation and perfusion, improve oxygenation and decrease pulmonary hypertension. However, existing approaches for the administration of inhaled NO are associated with the co-delivery of potentially toxic concentrations of nitrogen dioxide (NO2) due to the oxidation of NO in oxygen rich environments. We tested the ability of a novel methodology for generating highly purified NO through the reduction of NO2 by ascorbic acid to reverse pulmonary hypertension. In vitro testing demonstrated that the NO output of the novel device is ultrapure and free of NO2. An in vivo hypoxemic swine model of pulmonary hypertension was used to examine the dose response to NO in terms of pulmonary pressures and pulmonary vascular resistance. Pulmonary hypertension was induced by lowering inspired oxygen to 15% prior to treatment with inhaled ultra purified NO (1, 5, 20, and 80PPM). Hypoxemia increased mean pulmonary artery pressures and pulmonary vascular resistance. Inhaled ultra purified NO doses (down to 1PPM) show a marked reduction of hypoxemia-induced pulmonary vascular resistance. These experiments demonstrate a simple and robust method to generate purified inhaled NO that is devoid of NO2 and capable of reversing hypoxemia induced pulmonary hypertension.
authors.affiliation: Department of Anesthesiology and Pain Medicine, St. Elizabeth's Medical Center, 736 Cambridge Street, Boston, MA 02135-2997, United States. mark.lovich@steward.org
authors.forename: Mark A
authors.initials: MA
authors.lastname: Lovich
authors.forename: Natalie K
authors.initials: NK
authors.lastname: Bruno
authors.forename: Charles P
authors.initials: CP
authors.lastname: Plant
authors.forename: Abraham E
authors.initials: AE
authors.lastname: Wei
authors.forename: Gregory B
authors.initials: GB
authors.lastname: Vasquez
authors.forename: Bryan J
authors.initials: BJ
authors.lastname: Johnson
authors.forename: David H
authors.initials: DH
authors.lastname: Fine
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Gilbert
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D001205:Ascorbic Acid / Q000378:metabolism / Q000627:therapeutic use*; D004195:Disease Models, Animal; D006976:Hypertension, Pulmonary / Q000628:therapy*; D000860:Hypoxia / Q000628:therapy; D009569:Nitric Oxide / Q000138:chemical synthesis / Q000627:therapeutic use*; D009584:Nitrogen / Q000378:metabolism; D009585:Nitrogen Dioxide / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism; D011651:Pulmonary Artery / Q000503:physiopathology*; D013552:Swine; D014655:Vascular Resistance
chemical_list: D009569:Nitric Oxide; D009584:Nitrogen; D001205:Ascorbic Acid; D009585:Nitrogen Dioxide; D010100:Oxygen