Lung function, surfactant apoprotein content, and level of PEEP in prematurely delivered rabbits

To study the in vivo activity of the surfactant apoproteins (SP-A, SP-B, SP-C), we administered surfactants with defined apoprotein compositions to prematurely delivered rabbit pups. Rabbits given simple phospholipid mixtures containing dipalmitoylphosphatidylcholine and phosphatidylglycerol supplemented with both SP-B and SP-C or either protein alone had significantly greater lung compliance during ventilation and lung expansion during a quasi-static pressure-volume maneuver than did saline-or lipid-treated controls. The response to the surfactants containing SP-B/C was markedly dependent on the level of end-expiratory pressure used during ventilation. When the rabbits were ventilated with a positive end-expiratory pressure (PEEP) of 4 cmH2O, lung function in the pups treated with SP-B/C was not significantly different from rabbit surfactant-treated controls. Addition of SP-A to the surfactants containing SP-B/C did not significantly further improve lung function if the pups were ventilated with a PEEP of 4 cmH2O. With a lower PEEP of 1 cmH2O, lung function in the pups given surfactants containing SP-B/C was no longer equivalent to the lung function of the rabbit surfactant-treated controls. At the lower PEEP, SP-A significantly improved lung function when it was added to surfactants containing SP-B and SP-C. No beneficial effect of SP-A was seen when the surfactant contained either SP-B or SP-C alone. We conclude that with assisted ventilation that includes a moderate level of PEEP, SP-B and SP-C significantly enhance the effect of a simple phospholipid mixture on the lung function of prematurely delivered rabbits. At lower levels of PEEP the effects of SP-B and SP-C on lung function are markedly reduced but can be restored by the addition of SP-A. Our results are consistent with the existence of cooperative protein-protein interactions in surfactant function in vivo and suggest that the response to a surfactant will be determined by both the ventilation strategy and the surfactant composition. composition.