Effect of acute lung injury on structure and function of pulmonary surfactant films.

The structural and functional alterations in pulmonary surfactant that occur during acute lung injury were studied using rat lung surfactant large aggregates (LA) isolated from normal nonventilated lungs (N), and from standard ventilated (V) and injuriously ventilated (IV) excised lungs. N lungs inflated significantly better than IV lungs, with V lungs intermediate. Although IV LA phosphatidylcholine levels were unchanged, cholesterol and protein were elevated. V LA exhibited PC/cholesterol and PC/protein ratios intermediate between N and IV. In contrast to total cholesterol and protein levels, these ratios were not significantly different from IV LA. N and V LA, but not IV LA, adsorbed rapidly and were able to generate surface pressures (pi) near 70 mN/m during surface area reduction at 37 degrees C on a captive bubble tensiometer. Langmuir-Wilhelmy surface balance studies at 23 degrees C showed N LA films consistently attained pi approaching 70 mN/m during ten compression-expansion cycles. IV films were less effective and failed to achieve high pi consistently after the sixth cycle. V films were intermediate. Epifluorescence studies revealed compression of adsorbed N LA films formed well-defined liquid-condensed (LC) domains, but fewer, smaller domains were observed with IV films and, to a lesser extent, V films. Atomic force microscopy on Langmuir-Blodgett N films transferred at pi = 30 mN/m showed high, well-defined LC domains. IV films showed thinner, intermediate height, possibly fluid domains, which contain large numbers of small higher domains with heights corresponding to LC domains. V films were intermediate. We conclude that acute lung injury induced by hyperventilation, and to a lesser extent standard ventilation, of excised lungs alters surfactant surface activity and the ability of natural surfactant to form surface structures at the air-water interface.