Surfactant Protein C (SP-C) in Ventilated Premature Lamb Lung † 1677

Abstract

Background. Synthetic surfactants have theoretical advantages of uniform composition, consistency of properties, lower risk, and lower cost. Synthetic surfactants that contain only lipids and recombinant SP-C can be as effective as natural surfactants for the treatment of surfactant deficiency in preterm animals. However, there is no information about the fate of this very hydrophobic protein in the preterm lung. Hypothesis. Because other surfactant components are cleared very slowly from the preterm lung, we hypothesized that SP-C would also be cleared slowly. Methods. We compared alveolar and total lung clearances of 125I-natural SP-C(nSP-C), 125I recombinant SP-C(rSP-C, phenylalanine in positions 4 and 5 and isoleucine in position 32 of the human sequence, provided by Byk Gulden, Konstanz, Germany) with the clearance of14 C-dipalmitoylphosphatidylcholine (DPC). Preterm lambs at 128 d gestation were given treatment doses of 100 mg/kg 125I-nSP-C labeled natural sheep surfactant (n=6), 125I-rSP-C labeled natural sheep surfactant (n=9) or 125I-rSP-C labeled synthetic surfactant (n=9) and recoveries were measured at 5 h. Trace doses of 125I-rSP-C and14 C-DPC also were given to 135 d gestation lambs without surfactant treatment and recoveries were measured at 0 (n=3), 2 (n=5), 5 (n=6), or 10 h(n=5). Results. 5 h after surfactant treatments, the 3 groups of lambs had the same pC02 values (50-54 mmHg), the same ventilator pressure requirements (18-20) cmH20, and similar compliances(0.46-0.51), indicating equivalent physiological lung function. The alveolar recoveries were 17-24% for 14C-DPC and 13-16% for labeled125 I-nSP-C and rSP-C for the 3 groups of lambs. Total lung recoveries were about 70% for the 14C-DPC and labeled nSP-C and rSP-C. All recoveries for nSP-C and rSP-C were similar and similar to those for DPC. In 135 d GA lambs not treated with surfactant,% recovery of 14C-DPC in alveolar lavage decreased from 45.2±2.5(0 h) to 11.3±0.4 at 10 h. There was no loss of the 14C-DPC from the total lungs. The recoveries of 125I-rSP-C decreased from 42.0±2.4% (0 h) in the alveolar lavage to 6.4±1.0% (10 h). Although about 20% of the radiolabeled rSP-C was lost from the total lung over first 2 h, there were no further loss to 10 h. Conclusions. The surfactants containing rSP-C and nSP-C were functionally similar and the two SP-C proteins were cleared slowly and in parallel with DPC.