The lungs of the ventilated premature infant or animal leak intravascular protein into the air spaces. This protein includes an inhibitor that disrupts the surface tension lowering properties of surfactant. Considerations of surfactant pool sizes present in the premature lung together with estimates of the magnitude of stimulation of synthesis induced by agents such as corticosteroids and T3 together with data indicating structural maturation following the pharmacologic induction of lung maturation suggest that the dominant functional effect of these agents on lung maturation may not be mediated by surfactant. Others have reported that corticosteroids and T3 change the permeability properties of the leaky postnatal lung to those characteristic of the adult lung. Therefore, the hypothesis to be tested by these experiments is that corticosteroids and/or T3 decrease the protein leak into the airways of the ventilated premature lung and thus help to preserve surfactant function. The gestational age dependence of a corticosteroid effect will be tested using prematurely delivered and ventilated rabbits from 27 to 30 days gestational age delivered 2 days after the initiation of maternal betamethasone (0.2 mg/kg.24 hr) therapy. Half of each litter will be treated with natural rabbit surfactant to neutralize any surfactant induction by the corticosteroid. Protein leaks will be measured with radiolabeled albumin. A twin pair preterm lamb model will be used to better assess the effects of corticosteroids, T3 and corticosteroids plus T3 on lung function, surfactant function, and protein leak. One lamb of each twin pair will receive a fetal infusion of the agent while the other lamb will receive vehicle control. Both lambs then will be delivered, treated with natural sheep surfactant, and ventilated. The multiple measurements of lung function, surface activity, inhibitor, and the bidirectional protein leak will identify the magnitude of changes induced by corticosteroid and T3. These experiments measure the functional effects of the agents because the preterm animals are ventilated for a period of 3 hrs. These experiments are likely to identify effects of corticosteroids and T3 on the fetal lung that importantly influence postnatal lung function and the incidence of RDS. These results would significantly change current thoughts concerning the mechanism of induced lung maturation.
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