Am. J. Respir. Crit. Care Med., Volume 159, Number 5, May 1999, 1391-1395

Nonionic Polymers Reverse Inactivation of Surfactant by Meconium and Other Substances

H. WILLIAM TAEUSCH, KAREN W. LU, JON GOERKE, and JOHN A. CLEMENTS

Departments of Pediatrics and Physiology, and the Cardiovascular Research Institute, University of California-San Francisco, San Francisco, California

A variety of substances including human meconium have been found to affect adversely the surface tension-lowering activity of pulmonary surfactants, and this effect may be important in the pathogenesis of a number of human diseases. To find whether inactivation of surfactant could be prevented or reduced by nonionic polymers, we added dextrans, polyethylene glycols (PEGs), or polyvinylpyrrolidones (PVPs) of various molecular weights to pulmonary surfactants. One to 3% human meconium or other inactivating substances were then added to the mixtures, which were tested in a modified pulsating bubble surfactometer. Polymers (3.3-500 kD) in 1-10% concentrations enhanced the ability of a commercial surfactant replacement (Survanta) to lower the minimum surface tension in the presence of meconium, serum, or lysophosphatidylcholine. Similar effects were seen when polymers were added after mixing of surfactant and meconium or other inhibitors, indicating that polymers are capable of reversing the inactivation. Results from rat experiments indicate that total lung capacity is increased when PEG is first added to the Survanta, then mixed with meconium and instilled into the lungs. We postulate that polymers separate meconium-surfactant complexes, permitting surfactant components better access to the air-liquid interface. Taeusch HW, Lu KW, Goerke J, Clements JA. Nonionic polymers reverse inactivation of surfactant by meconium and other substances.

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