404 SUPEROXIDE DISMUTASE MIMETIC IMPROVES PULMONARY FUNCTION IN A MODEL OF BRONCHOPULMONARY DYSPLASIA IN THE PREMATURE NEONATE

Superoxide anion and other oxygen free radicals have been implicated in the pathogenesis of bronchopulmonary dysplasia. We tested the hypothesis that a catalytic antioxidant metalloporphyrin AEOL 10113b can protect against hyperoxia-induced lung injury using a premature baboon model of bronchopulmonary dysplasia.MethodsPregnant dams were treated with betamethasone (6 mg IM) 48 and 24 hours prior to hysterotomy. Controls (C) were delivered at 125 ± 2 d of gestation (term = 185 d), intubated, treated with surfactant and placed on mechanical ventilation for 14 days. Treated animals were managed similarly except they received AEOL 10113b, 0.5 mg/kg mixed with surfactant and 0.25 mg/kg/day continuous infusion for the remainder of the 14-day protocol. Lung compliance/kg measured by body plethysmograph, hemodynamic data, and echocardiographic data were serially recorded. Ventilation index (VI) and oxygenation index (OI) were calculated from ventilator settings and abgs.ResultsThere was no difference in birth weight and gestation for C (n = 10) vs AEOL (n = 6). There was no difference in hemodynamic or cardiac function. There was no difference in oxygenation index; however, there was a lower VI (p < .05, ANOVA) associated with higher c/kg (p < .01, ANOVA) in the AEOL treated group. In addition, the AEOL group had a higher rate of spontaneous patent ductus arteriosus closure (p < .05, chi square).ConclusionThe superoxide dismutase mimetic AEOL 10113b improved pulmonary function in premature baboons at risk for bronchopulmonary dysplasia. Further studies include lung morphometry and assessment of markers of oxidative stress. Funded by NIH HL52636, P51RR13986, 2 U01 HL063397-05.