title: Aerosolized soluble nitric oxide donor improves oxygenation and pulmonary hypertension in acute lung injury.
abstract: Acute respiratory distress syndrome (ARDS) is a major cause of morbidity and mortality in critically ill patients. The associated ventilation/perfusion mismatch and pulmonary hypertension are amenable to treatment with inhaled nitric oxide (NO) gas. Compounds formed by reacting NO with various nucleophiles (NONOates) release NO spontaneously and induce vasodilation. Intratracheally administered NONOates result in selective reduction in pulmonary hypertension. We hypothesized that a nebulized NONOate would improve oxygenation and reduce pulmonary vascular resistance in oleic acid-induced acute lung injury and pulmonary hypertension. Pigs underwent catheterization of the pulmonary artery, left atrium, and right atrium, and a flow probe was positioned around the pulmonary artery. Acute lung injury and pulmonary hypertension were induced with intravenous oleic acid. Animals were randomly assigned to receive either nebulized saline or the NONOate 2-(dimethylamino)ethylputreanine/NO (DMAEP/NO). Hemodynamic, gas exchange, pulmonary function, methemoglobin, and nitrite/nitrate measurements were obtained for 60 min. Animals in the DMAEP/NO group had improvement in PaO2 as compared with control animals (from 139 +/- 19 mm Hg to 180 +/- 19 mm Hg in the DMAEP/NO group [n = 6]; and from 144 +/- 6 mm Hg to 150 +/- 9 mm Hg in the saline group [n = 6], p < 0.05). After aerosol treatment, animals in the DMAEP/NO group had a greater reduction in pulmonary vascular resistance index (PVRI) than did control animals (from 81 +/- 17 dyne. s/cm5/kg to 34 +/- 8 dyne. s/cm5/kg; and from 104 +/- 16 dyne. s/cm5/kg to 64 +/- 11 dyne. sec/cm5/ kg in the saline group at 60 min, p < 0.05). There were no differences between the groups in systemic vascular resistance index (SVRI), cardiac index (CI), methemoglobin, nitrite/nitrate, or lung pathology scores. We conclude that DMAEP/NO improves oxygenation and has selective pulmonary vasodilating properties without causing significant systemic toxicity in this porcine model of acute lung injury.
authors.affiliation: Division of Critical Care Medicine and Department of Pathology, Children's Hospital Medical Center, Cincinnati, Ohio, USA. jacobs@chmcc.org
authors.forename: B R
authors.initials: BR
authors.lastname: Jacobs
authors.forename: R J
authors.initials: RJ
authors.lastname: Brilli
authors.forename: E T
authors.initials: ET
authors.lastname: Ballard
authors.forename: D J
authors.initials: DJ
authors.lastname: Passerini
authors.forename: D J
authors.initials: DJ
authors.lastname: Smith
mesh_terms: D000280:Administration, Inhalation; D000336:Aerosols; D000599:Amino Acids, Diamino / Q000008:administration & dosage / Q000627:therapeutic use; D000818:Animals; D006328:Cardiac Catheterization; D002302:Cardiac Output / Q000187:drug effects; D002407:Catheterization, Swan-Ganz; D004195:Disease Models, Animal; D006976:Hypertension, Pulmonary / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D007275:Injections, Intravenous; D008168:Lung / Q000098:blood supply / Q000187:drug effects / Q000473:pathology; D008297:Male; D008706:Methemoglobin / Q000032:analysis; D009330:Nebulizers and Vaporizers; D009566:Nitrates / Q000032:analysis; D009569:Nitric Oxide / Q000008:administration & dosage / Q000627:therapeutic use; D020030:Nitric Oxide Donors / Q000008:administration & dosage / Q000627:therapeutic use*; D009573:Nitrites / Q000032:analysis; D019301:Oleic Acid / Q000008:administration & dosage / Q000009:adverse effects; D010101:Oxygen Consumption / Q000187:drug effects*; D011659:Pulmonary Gas Exchange / Q000187:drug effects; D011897:Random Allocation; D012128:Respiratory Distress Syndrome / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D012995:Solubility; D013552:Swine; D014655:Vascular Resistance / Q000187:drug effects; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000627:therapeutic use; D014692:Ventilation-Perfusion Ratio / Q000187:drug effects
chemical_list: C110153:2-(dimethylamino)ethylputreanine-nitric oxide adduct; D000336:Aerosols; D000599:Amino Acids, Diamino; D009566:Nitrates; D020030:Nitric Oxide Donors; D009573:Nitrites; D014665:Vasodilator Agents; D019301:Oleic Acid; D009569:Nitric Oxide; D008706:Methemoglobin