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Preterm lambs have a greater incidence of pulmonary hypertension and pulmonary vascular reactivity. They also develop pulmonary hypertension in response to hypoxemia during perinatal asphyxia. We hypothesized that treating the pulmonary hypertension of these neonates with prostacyclin would result in better pulmonary vascular reactivity and improved neonatal survival in a neonatal lung ex vivo model of severe preterm pulmonary hypertension. Preterm lambs were delivered by cesarean section and endotracheally intubated. Lambs were exposed to 1 hour of air or 100% oxygen and treated with aerosolized placebo or aerosolized prostacyclin (0.4 mg/kg) after return to air. Lungs were isolated and challenged with 80 ppm of hypoxia for 1 hour. Baseline and treated lungs were then harvested and assessed for vascular structure and pulmonary function. In lambs receiving aerosolized placebo during hypoxia, static pressure-volume curves were abnormal and pulmonary vascular reactivity was impaired. In contrast, when lambs received aerosolized prostacyclin, static pressure-volume curves were normal, and pulmonary vascular reactivity was improved in response to 80 ppm of hypoxia. Early neonatal mortality in placebo-treated animals was 31% (5 of 16), and all survivors had persistent pulmonary hypertension. In animals receiving aerosolized prostacyclin, early neonatal mortality was 18% (2 of 11), and 6 of 11 survivors had normalization of pulmonary artery pressures (5.2 +/- 2.6 mm Hg at 1 hour) and 6 had improvement in pulmonary vascular reactivity. This study demonstrates that aerosolized prostacyclin, which is currently used in the treatment of pulmonary hypertension, improves neonatal survival in this model of severe preterm pulmonary hypertension.Friday, June 29, 2009
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