Abstract 1747
Poster Session IV, Tuesday, 5/4 (poster 336)
In preterm infants with respiratory distress syndrome, biophysical and biochemical injury of the alveolar epithelium and its lining may result in inactivation of both endogenous and replacement surfactant. Improved surfactant performance has been linked to the presence of native surfactant proteins A and B (SP-A and SP-B), to specific molecular characteristics of surfactant components, and to timing of its instillation. The behavior of synthetic mimics of surfactant proteins in the presence of inactivators has not yet been defined. After annealing a series of human synthetic surfactant peptides (SP-B1-25, full-length SP-B1-78, a mutant SP-B [R236C], palmitoylated SP-C1-34, alone or combined) with a standard lipid dispersion of phospholipids and palmitic acid (PL), using Survanta and PL as controls, we tested these preparations on a modified Langmuir/Wilhelmy balance against albumin, serum, plasma, and fibrinogen in approximated physiological ratios. Each surfactant was cycled 3 times before applying the inactivator (prophylaxis), or, alternatively, surfactant was applied to the surface after loading and cycling the inactivator (rescue). Area of hysteresis and minimum surface tension were analyzed on the 1st and 3rd cycle. All the surfactants tested presented sensitivity to albumin < serum < plasma < fibrinogen. In the rescue mode, PL and SP-C1-34 were severely inactivated, Survanta and SP-B1-78 showed recovery over the initial traces, and only synthetic SP-B1-25 showed strong resistance to inactivation. In the prophylaxis tests, SP-B1-78 and SP-C1-34 were slightly inhibited, as shown by a decrease in the area of the hysteresis, but without effects on the minimum surface tension. All other surfactants, including the Survanta and PL controls, were minimally affected by the addition of these inactivators. Our data suggest that, although sensitivity to inactivators may vary among surfactants, establishing a functional surface monolayer before endogenous proteins leak into the air space may represent the critical element in surfactant replacement therapy.
