Terbutaline; a beta2-adrenergic agonist, and aminophyllin, a phosphodiesterase inhibitor, were given separately, or in combination, to rabbit fetuses on the 28th day of gestation. The possibility of these drugs causing a release of pulmonary surfactant was evaluated 3 h after i.m. injection directly to the fetus. Lung compliance was studied and lung lavage fluid assessed as regards content to total phospholipid phosphorus, lecithin/sphingomyelin (L/S) ratio, and surface activity. It was found that terbutaline, in a dose of 0.1 mg, had a significant (p less then 0.05) effect on each of the four parameters studied and, when given in a dose of 0.05 mg, significantly affected all except L/S ratio. Aminophyllin, in a dose of 10 mg, resulted in a 40% mortality, but in the surviving fetuses the drug had no significant (p greater than 0.05) effect on any of the four parameters. When 5 mg aminophyllin was given together with 0.05 mg terbutaline, the effect could be attributed to terbutaline.
Preterm rabbit fetuses, delivered on the 27th day of gestation, were studied following upper airway instillation with either natural surfactant (NSA) obtained from the lavage of adult rabbit lungs or with a protein-free suspension of lipids extracted from lung wash (ESA). First, lung compliance was studied postmortem. The administration of 25 microliters of either preparation resulted in greater hysteresis (P less than 0.05) than was observed in control fetuses receiving no surfactant material. Increasing the phospholipid concentration stepwise from 10 to 50 mg/ml improved airway expansion and stability. No further improvement was encountered with concentrations greater than 50 mg/ml. There was no significant difference in compliance response between NSA and ESA. Morphometry of the lungs also indicated that the two preparations had an equal effect on compliance. Second, it was determined how neonatal survival was affected by a pharyngeal deposition, prior to the first breath, of 50 microliters NSA or ESA. Both treatment groups demonstrated improved survival (P less than 0.001) when compared with controls receiving no pharyngeal deposition. These findings offer further support to the concept that protein is not required for the efficacy of a surfactant supplementation. The equivalence of the two preparations suggests that a sterile suspension of a protein-free surfactant extract could be used to prevent or treat respiratory distress in preterm neonates.
Preterm rabbit neonates, delivered on the 27th day of gestation, were treated before the first breath with a tracheal instillation of ESA, a suspension of lipids extracted from pulmonary surfactant. Lung compliance development and neonatal survival were studied after treatment to determine the effect of suspension volume and concentration. Compliance development was not dependent on either delivery volume or suspension concentration, but rather on the quantity of phospholipids instilled. Indices of improved expansion and stability demonstrated a dose response relationship up to 1.1 mg phospholipid per g lung. Larger doses neither improved nor detracted from the response. The ability of the neonates to survive and adapt to an air breathing environment was influenced by the instillation volume. Viability was reduced when the treatment volume exceeded 16% of the functional residual capacity. Prophylactic surfactant supplementation therapy may be useful in preventing the development of neonatal respiratory distress syndrome. Surfactant extract may prove acceptable for both prophylaxis and treatment of established respiratory distress syndrome.
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