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 bronchop ulmonary dysplasia (BPD) and superimposed infection. A total of 20 bab oons were delivered by hysterotomy at 76% of gestation (140 d of gesta tional age) and were randomized into four groups, consisting of two co ntrol and two injury groups, Animals constituting a group that was man aged on a pro re nata (PRN) basis were ventilated with clinically appr opriate oxygen for the 16-d experimental period and served as ventilat ory controls. They underwent an initial period of 42 h during which th ey 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 prot eins, messenger ribonucleic acids (mRNAs), and phospholipids were simi lar to those of normal adult baboons. Gestational control animals were delivered and killed without ventilation at 156 d gestational age. Su rfactant protein-A (SP-A) and phospholipid concentrations in these ani mals' lavage fluids were about 10% of those in the PRN animals. Animal s with BPD were subjected to positive-pressure ventilation and an Fl(O 2) of 1.0 for 11 d, followed by 5 d of an Fl(O2) sufficient to maintai n Pa-O2 at 40 to 50 mm Hg. The animals with BPD and infection were tre ated in the same way as the BPD group, except that 10(8) Escherichia c oli were instilled intratracheally on Day 11, concomitantly with the r eduction in Fl(O2). As compared with normal adults or the PRN controls , the animals in both of these injury groups showed significant reduct ions in SP-A mRNA and in SP-A content, whereas the mRNAs for surfactan t 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 see n in them upon treatment with sodium dodecyl sulfate followed by polya crylamide gel electrophoresis. Surfactant phospholipids in the injury groups were no different from those in the PRN controls. Surface prope rties of surfactant from the injured animals, however, were abnormal i n that only those from three of 10 animals reduced surface tension to less than 10 dynes/cm. Part of the pathophysiology seen in these anima ls may have resulted from changes in the surfactant system.