Evaluation of alveolar surfactant aggregates in vitro and in vivo.

In acute lung injury, a decrease in surface-active large aggregates and an increase in the less surface-active small surfactant aggregates are observed. The objective of the current study was to determine if the increase in small aggregates interfered with the function of large aggregates, thereby independently contributing to lung dysfunction. Isolated large aggregates, small aggregates, and large aggregate+small aggregate combinations were analysed for in vitro surface activity utilizing a pulsating bubble surfactometer. Subsequently, large aggregates, small aggregates, and large aggregate+ small aggregate combinations were administered to surfactant-deficient, adult Sprague-Dawley rats. Physiological parameters were measured during 1 h of ventilation. After sacrifice, the whole lung lavage was analysed for protein concentration, and surface activity of the recovered large aggregates. The minimum surface tension of the large aggregate+small aggregate preparations (10 mN x m(-1)) was significantly higher than large aggregates alone (1 mN x m(-1)), but lower than small aggregates alone (21 mN x m(-1) ) after 100 pulsations. In vivo, rats receiving large aggregates+small aggregates showed immediate increases in oxygenation, similar to animals given large aggregates, whereas animals given small aggregates and control animals maintained low oxygenation values. In conclusion, small aggregates interfered with large aggregates function in vitro, but this was not observed in vivo in this experimental model.

Surfactant treatment for ventilation-induced lung injury in rats: effects on lung compliance and cytokines.

The objective of this study was to determine if exogenous surfactant therapy could prevent the harmful effects of ventilation at high tidal volumes without positive end-expiratory pressure (PEEP). Rats were randomized to either a nontreated control group (8 mL/kg 4 cm H2O PEEP), a nontreated injuriously ventilated group (20 mL/kg 0 cm H2O PEEP) or a treatment group of either 50 mg/kg, 50 mg/kg + 5% surfactant-associated protein A, 100 mg/kg exogenous surfactant followed by injurious ventilation. Isolated lungs from animals in all 5 groups were ventilated in a humidified box at 37 degrees C for 2 hours. Pressure-volume curves and light microscopy showed that surfactant treatment reduced the ventilation-induced lung injury (VILI). Inflammatory cytokines (tumor necrosis factor-alpha [TNFalpha], interleukin [IL]-1beta, and IL-6) in the lavage were significantly higher in injuriously ventilated lungs compared to the control group. However the 3 treatment groups had cytokine concentrations that were similar to the injuriously ventilated group. We conclude that surfactant treatment is beneficial in preventing VILI; however, it does not prevent the release of inrflammatory cytokines during mechanical ventilation.

Effects of ventilation on the surfactant system in sepsis-induced lung injury.

The present study examined the effects of mechanical ventilation, with or without positive end-expiratory pressure (PEEP), on the alveolar surfactant system in an animal model of sepsis-induced lung injury. Septic animals ventilated without PEEP had a significant deterioration in oxygenation compared with preventilated values (arterial PO(2)/inspired O(2) fraction 316 +/- 16 vs. 151 +/- 14 Torr; P < 0.05). This was associated with a significantly lower percentage of the functional large aggregates (59 +/- 3 vs. 72 +/- 4%) along with a significantly reduced function (minimum surface tension 17.7 +/- 1.8 vs. 11.8 +/- 3.8 mN/m) compared with nonventilated septic animals (P < 0.05). Sham animals similarly ventilated without PEEP maintained oxygenation, percent large aggregates and surfactant function. With the addition of PEEP, the deterioration in oxygenation was not observed in the septic animals and was associated with no alterations in the surfactant system. We conclude that animals with sepsis-induced lung injury are more susceptible to the harmful effects of mechanical ventilation, specifically lung collapse and reopening, and that alterations in alveolar surfactant may contribute to the development of lung dysfunction.