Reversal of meconium inhibition of pulmonary surfactant by ferric chloride, copper chloride, and acetic acid

Meconium inhibits pulmonary surfactant function. We investigated the in vit ro effect of meconium on three different commercial surfactants. The dynami c surface properties of these surfactants were evaluated at the concentrati on 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 Su rvanta. Ferric chloride and copper chloride completely reversed the inhibit ory effect of meconium. Meconium also prevented effective spreading of surf actant in a Wilhelmy balance system, and this inhibitory effect was counter acted by addition of ferric chloride. Image analysis of Curosurf demonstrat ed that meconium reduced the total number of microbubbles in 15 light-micro scopic fields (4.35 mm(2)) from 1,748 +/- 481 to 180 +/-: 166. Ferric chlor ide restored the number of microbubbles. Addition of ferric chloride or cop per chloride to surfactant/meconium lowers pH, and pH adjustment by acetic acid also reversed the inhibitory effect of meconium. Together with the fac t that the iron-chelator deferoxamine did not attenuate the effect of ferri c chloride this suggests that the observed contrainhibition is caused by lo wering of pH, and that meconium inhibition of surfactant is pH-dependent. L owering pH from 6.2 to 5-5.5 abolished the inhibitory effects of meconium o n 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 in hibitory effect of meconium on surfactant in vitro can be abolished by addi tion of ferric chloride, copper chloride, or acetic acid.