The long term objective of the proposed research is to obtain a better understanding of the function of pulmonary surfactant in the lungs. The rationale for the project is based on obvious inconsistencies between the bubble model of the alveolus an known lung structure and an observation recently reported following administration of Tween 20 to surfactant deficient premature lambs. Independent of how valid the bubble model of the alveolus is or is not, the observation that Tween 20 resulted in significant improvement in lung function in premature lambs deserves further investigation. These studies will assess the relationship between the surface tensions of various surface active agents and their ability to improve the lung function of lambs with respiratory distress syndrome. They will also determine how these agents effects the cardiovascular system. Finally, they will begin to assess pulmonary mechanics in lambs with RDS and how this is altered by administration of natural surfactant. Achieving these goals will provide insight into normal lung and surfactant function and may provide guidance toward the production of a safe, artificial surfactant which can be used to treat RDS. Methodology to be used in all proposed experiments is fairly standard. It involves delivering lambs prematurely at several gestational ages and supporting them after a variety of different treatments (including administration of unusual surface active agents), similar to the way human infants are supported when born prematurely. Arterial blood gas and some pulmonary mechanic measurements will be made in the live animals. Cardiovascular function will be measured using microspheres. Postmortem measurements will include estimates of surfactant content and surface tensions which will be correlated with physiologic data.
| Jacobs, H C; Mercurio, M R (1993) Perfluorocarbons in the treatment of respiratory distress syndrome. Semin Perinatol 17:295-302 |
| Gladstone, I M; Ray, A O; Salafia, C M et al. (1990) Effect of artificial surfactant on pulmonary function in preterm and full-term lambs. J Appl Physiol 69:465-72 |
| Gladstone, I M; Ehrenkranz, R A; Jacobs, H C (1989) Pulmonary function tests and fluid balance in neonates with chronic lung disease during dexamethasone treatment. Pediatrics 84:1072-6 |
| Mercurio, M R; Fiascone, J M; Lima, D M et al. (1989) Surface tension and pulmonary compliance in premature rabbits. J Appl Physiol 66:2039-44 |
| Gladstone, I M; Mercurio, M R; Devenny, S G et al. (1989) Antenatal steroids, postnatal surfactant, and pulmonary function in premature rabbits. J Appl Physiol 67:1377-82 |
