Purpose: By quenching superoxide anion, superoxide dismutase(SOD) may increase the bioavailability and pulmonary hemodynamic effects of NO inhaled in combination with high oxygen tensions. We studied the hemodynamic effects of human recombinant SOD and inhaled NO in a newborn lamb model of PPHN in which the ductus arteriosus is ligated 9 days prior to delivery.Methods: At delivery (136 days) lambs were fully instrumented for measurement of pulmonary artery pressure (PA), pulmonary blood flow (Qp), left atrial pressure, and aortic pressure. FiO2 was 1.0 for the duration of the study and ventilator rates and pressures were adjusted to keep PaCO2 35-50 mm Hg. Lambs were randomized to one of 3 study groups (n=4 in each group): SOD alone (5 mg/kg intratracheal instillation at first breath), NO alone (30 minute inhalation of 5 ppm after one hour stabilization period, followed by a 30 minute period off NO, then 4 hour inhalation of 80 ppm), and SOD/NO (both therapies). Bronchoalveolar lavage and lung tissue samples were collected at the end of the study to assess for markers of inflammation and lung injury. Results: There were trends toward lower PAP and lower PaCO2 in both the SOD and SOD/NO groups at baseline. Pulmonary hemodynamics and oxygenation did not change over time in the SOD group. NO alone and SOD/NO at 5 ppm and 80 ppm lowered PAP and increased PaO2 (Table, all values±SD,*=p<0.05 vs. baseline by repeated measures ANOVA). While there was no significant difference between the two groups, PaO2 increased significantly from baseline only in the SOD/NO group. Conclusion: SOD may improve pulmonary hemodynamics at baseline, and may improve the oxygenation response to inhaled NO. Analysis for inflammatory effects may show potential benefit in terms of long term lung damage following inhalation of NO and oxygen at high concentrations.

Table 1 No caption available.