Surfactant aggregate size correlates with function in vivo. We have compared the effects of mechanical ventilation on the aggregate size of synthetic surfactants in the surfactant depleted rat lung model, lavaged before surfactant treatment and after 1 hour of ventilation (FiO2 = 1.0, rate = 60, VT =7.5 mL/Kg). Aggregate size was measured on a Mitech laser beam sample sizer. We used phospholipids and palmitic acid (PL) alone, or PL plus synthetic peptides: PL + 3% B1-78 (B), PL + 3% B1-78& 1% C1-35 (BC), PL + 3% KL4 (KL4), PL + 3%B1-78 & 1% KL4 (BKL4), and PL + 3% of a serine analog of B1-78(Bser) at 25 mg PL/ml, using a dose of 100 mg/kg body weight. PL and sham treatment were used as controls. Surfactants, initial and final wash were assessed for particle size, and total proteins were measured in each lavage. Synthetic surfactant vesicles had an apparent diameter (AD) of 4-6 μm or more that did not change after surface cycling for 3 hours. In all groups, the first wash contained large particles with an AD of 1-6 μm. In the second wash, the sham treated and the BKL4 groups contained primarily small vesicles with an AD less than 0.2 μm. B, KL4, and Bser treated rats had a significant fraction of vesicles with an AD of 1-4 μm. PL had vesicles with an AD of both less than 0.1 and 1-2 μm. Protein content increased 2-20 folds after ventilation, but the increase did not correlate with vesicle size. These data suggest that synthetic surfactant proteins in PL may undergo only partial large-to-small from conversion in an animal model of surfactant depletion during mechanical ventilation.
