Aerosolized Soluble Nitric Oxide Donor Improves Oxygenation and Pulmonary Hypertension in Acute Lung Injury

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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 nu- cleophiles (NONOates) release NO spontaneously and induce vasodilation. Intratracheally adminis- tered 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 pulmo- nary 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-(dimethyl- amino)ethylputreanine/NO (DMAEP/NO). Hemodynamic, gas exchange, pulmonary function, meth- emoglobin, and nitrite/nitrate measurements were obtained for 60 min. Animals in the DMAEP/NO group had improvement in Pa O 2 as compared with control animals (from 139 6 19 mm Hg to 180 6 19 mm Hg in the DMAEP/NO group (n 5 6); and from 144 6 6 mm Hg to 150 6 9 mm Hg in the sa- line group (n 5 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 6 17 dyne · s/cm 5 /kg to 34 6 8 dyne · s/cm 5 /kg; and from 104 6 16 dyne · s/cm 5 /kg to 64 6 11 dyne · sec/cm 5 / kg in the saline group at 60 min, p , 0.05). There were no differences between the groups in sys- temic vascular resistance index (SVRI), cardiac index (CI), methemoglobin, nitrite/nitrate, or lung pa- thology scores. We conclude that DMAEP/NO improves oxygenation and has selective pulmonary va- sodilating properties without causing significant systemic toxicity in this porcine model of acute lung injury. Jacobs BR, Brilli RJ, Ballard ET, Passerini DJ, Smith DJ. Aerosolized soluble nitric oxide donor improves oxygenation and pulmonary hypertension in acute lung injury. AM J RESPIR CRIT CARE MED 1998;158:1536-1542.