SURFACTANT PROTEIN-A DEFICIENCY IN A PRIMATE MODEL OF BRONCHOPULMONARY DYSPLASIA

Pathophysiologic and biochemical (surfactant protein and phospholipid) features were studied in a baboon model of hyperoxia-induced bronchopulmonary dysplasia (BPD) and superimposed infection. A total of 20 baboons were delivered by hysterotomy at 76% of gestation (140 d of gestational age) and were randomized into four groups, consisting of two control and two injury groups, Animals constituting a group that was managed on a pro re nata (PRN) basis were ventilated with clinically appropriate oxygen for the 16-d experimental period and served as ventilatory controls. They underwent an initial period of 42 h during which they demonstrated evidence of hyaline membrane disease (HMD), but began recovery at 42 h and by Day 6 appeared to have maximally recovered. At the time of these animals' killing, concentrations of surfactant proteins, messenger ribonucleic acids (mRNAs), and phospholipids were similar to those of normal adult baboons. Gestational control animals were delivered and killed without ventilation at 156 d gestational age. Surfactant protein-A (SP-A) and phospholipid concentrations in these animals' lavage fluids were about 10% of those in the PRN animals. Animals with BPD were subjected to positive-pressure ventilation and an Fl(O2) of 1.0 for 11 d, followed by 5 d of an Fl(O2) sufficient to maintain Pa-O2 at 40 to 50 mm Hg. The animals with BPD and infection were treated in the same way as the BPD group, except that 10(8) Escherichia coli were instilled intratracheally on Day 11, concomitantly with the reduction in Fl(O2). As compared with normal adults or the PRN controls, the animals in both of these injury groups showed significant reductions in SP-A mRNA and in SP-A content, whereas the mRNAs for surfactant protein-B (SP-B) and surfactant protein-C (SP-C) were not affected. SP-B and SP-C were not quantified, but no qualitative changes were seen in them upon treatment with sodium dodecyl sulfate followed by polyacrylamide gel electrophoresis. Surfactant phospholipids in the injury groups were no different from those in the PRN controls. Surface properties of surfactant from the injured animals, however, were abnormal in that only those from three of 10 animals reduced surface tension to less than 10 dynes/cm. Part of the pathophysiology seen in these animals may have resulted from changes in the surfactant system.