Soluble nitric oxide donor and surfactant improve oxygenation and pulmonary hypertension in porcine lung injury.
Acute lung injury (ALI) is associated with diminished surfactant activity and pulmonary hypertension. NONOates are soluble NO donors which release NO in solution. Intratracheal NONOates reduce pulmonary hypertension and improve oxygenation in ALI. We hypothesized that the pharmacologic properties of NO donors would be unaltered after surfactant admixture in vitro and that aerosolized NONOate activity would be enhanced by surfactant pretreatment in vivo. NO donors were added to saline or surfactant and analyzed for nitrite/nitrate production and aortic ring vasodilation. Surfactant did not alter nitrate/nitrite production or aortic ring vasodilation. A porcine model of ALI with pulmonary hypertension was produced using intravenous oleic acid. Animals were assigned to Surfactant-Saline, Surfactant-NONOate, Saline-Saline, or Saline-NONOate groups. Saline or surfactant was instilled into the trachea, followed by gas exchange, pulmonary function, and hemodynamic measurements. NONOate or saline was then aerosolized, and additional data were collected. Oxygenation was improved in the Surfactant-NONOate group, while pulmonary hypertension was selectively reduced in both NONOate groups. Aerosolized NONOate following surfactant pretreatment improves oxygenation and reduces pulmonary hypertension in ALI.
Jacobs
B R
BR
Division of Critical Care Medicine, Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA. jacobs@chmcc.org
Smith
D J
DJ
Zingarelli
B
B
Passerini
D J
DJ
Ballard
E T
ET
Brilli
R J
RJ
D000599:Amino Acids, Diamino / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D004357:Drug Synergism; D006439:Hemodynamics / Q000187:drug effects; D006976:Hypertension, Pulmonary / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D066298:In Vitro Techniques; D008168:Lung / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D008706:Methemoglobin / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism; D009569:Nitric Oxide / Q000494:pharmacology; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D019301:Oleic Acid; D010396:Penicillamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D011659:Pulmonary Gas Exchange / Q000187:drug effects*; D011663:Pulmonary Surfactants / Q000494:pharmacology*; D011897:Random Allocation; D051381:Rats; D012128:Respiratory Distress Syndrome / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D026423:S-Nitroso-N-Acetylpenicillamine; D013552:Swine
C110153:2-(dimethylamino)ethylputreanine-nitric oxide adduct; D000599:Amino Acids, Diamino; D020030:Nitric Oxide Donors; D011663:Pulmonary Surfactants; D019301:Oleic Acid; D009569:Nitric Oxide; D026423:S-Nitroso-N-Acetylpenicillamine; D008706:Methemoglobin; D010396:Penicillamine