Recombinant Human CuZn Superoxide Dismutase (rhSOD) as an Adjunctive Therapy for Inhaled Nitric Oxide (NO)

Abstract 1727 Poster Session I, Saturday, 5/1 (poster 88)

By scavenging superoxide, rhSOD may decrease oxygen radical injury and improve the bioavailability of NO. We studied the effects of combined rhSOD and NO therapies on pulmonary hemodynamics and markers of lung inflammation in a lamb model of pulmonary hypertention(ductus arteriosis ligation). At delivery, lambs were instrumented for pulmonary artery(PA), left atrial, and aortic pressure and PA flow measurements. FiO₂ was maintained at 1.0 and the ventilator was adjusted to keep PaCO₂=35-50 mm Hg. Lambs received either rhSOD alone (5 mg/kg intracheally; n=5), NO alone (5 ppm for 30 minutes then 80 ppm for 4 hours;n=6), or rhSOD/NO combined (n=7). At 6 hours, lambs were sacrificed and bronchoalveolar lavage (BAL) was performed for cell counts, rhSOD, albumin and protein concentrations. Lung tissue was analyzed for rhSOD and markers of oxidative injury (malondialdehyde). PA pressure and pulmonary vascular resistance were significantly decreased in lambs receiving 80 ppm NO or rhSOD/NO. PaO₂ was significantly increased and the PA/Ao ratio decreased only in the rhSOD/NO lambs(figure). All other ventilatory and hemodynamic variables were not different among groups. There was a trend for lower protein and albumin concentrations in BAL from rhSOD treated lambs. Our data suggest that the combination of rhSOD and NO produces less extrapulmonary shunt and better systemic oxygenation than either agent alone. Significant rhSOD concentrations are present in the lung at 6 hours which appears to decrease alveolar protein leak. This suggests novel new approaches to the treatment of severe pulmonary hypertension in newborns. (Table)

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