Lung surfactant: How it does and does not work

Abstract

Earlier analyses of the physical chemistry of lung surfactant (LS) are rejected on the grounds that the definition of surface tension is not complied with. Furthermore, with 1 or 2 exceptions the devices used to measure the properties of LS have given misleading information. On the other hand, a protein-free formulation of an artificial lung-expanding compound (ALEC) consisting of a 7:3 mole/mole mixture of dipalmitoylphosphatidylcholine and phosphatidylglycerol seems to function as a reasonably good substitute for natural LS in very premature babies. It has the following necessary properties. It spreads rapidly and spontaneously at an air/water interface at 37°C, reducing the surface tension of water by about 2/3. The unsaturated phosphatidylglycerol (PG) moiety can be squeezed out of the mixed monolayer by rapid overcompression (equivalent to exhalation) and is irreversibly lost to the surface system by reassembly into liposomes. The residual dipalmitoylphosphatidylcholine (DPPC) becomes progressively enriched to the point that, at 37°C, it condenses out as a solid phase so rigid that it prevents the alveolae from collapsing. The preparation is protein-free.

It is suggested that this simple mixture of 2 phospholipids exhibits both thermodynamic (equilibrium) forces and the consequences of kinetic forces during the course of a compression/decompression cycle on a trough. Likewise, during a respiratory cycle, the alveolae may be kept open (or more precisely, the liquid lining the alveolae is prevented from filling them up) at full expiration by the presence of a permanent residue of almost pure DPPC which, being condensed (solid) at 37°C, is incompressible. The work of extending the uncovered air/water interface, upon inspiration, is reduced by replenishment from the stockpile of dry surfactant as though from a lamellar body. The respiratory cycle is thus seen as a dynamic sequence of refinement, ablution, and replenishment of phospholipid molecules.