Reversal of Meconium Inhibition of Pulmonary Surfactant by Ferric Chloride, Copper Chloride, and Acetic Acid

Meconium inhibits pulmonary surfactant function. We investigated the in vitro effect of meconium on three different commercial surfactants. The dynamic surface properties of these surfactants were evaluated at the concentration of 5 mg/ml with a pulsating bubble system. The inhibitory effect of 2.75 mg/ml meconium was significantly less on Alveofact than on Curosurf and Survanta. Ferric chloride and copper chloride completely reversed the inhibitory effect of meconium. Meconium also prevented effective spreading of surfactant in a Wilhelmy balance system, and this inhibitory effect was counteracted by addition of ferric chloride. Image analysis of Curosurf demonstrated that meconium reduced the total number of microbubbles in 15 light-microscopic fields (4.35 mm(2)) from 1,748 +/- 481 to 180 +/- 166. Ferric chloride restored the number of microbubbles. Addition of ferric chloride or copper chloride to surfactant/meconium lowers pH, and pH adjustment by acetic acid also reversed the inhibitory effect of meconium. Together with the fact that the iron-chelator deferoxamine did not attenuate the effect of ferric chloride this suggests that the observed contrainhibition is caused by lowering of pH, and that meconium inhibition of surfactant is pH-dependent. Lowering pH from 6.2 to 5-5.5 abolished the inhibitory effects of meconium on surfactant. Inhibition of 2.5 mg/ml of Curosurf with plasma could also be reversed by increasing amounts of ferric chloride. We conclude that the inhibitory effect of meconium on surfactant in vitro can be abolished by addition of ferric chloride, copper chloride, or acetic acid.