Surfactant release into the alveolar space protects the lung from ventilation-induced injury

Abstract

OBJECTIVE: The aim of this study was to investigate mechanisms involved in resistance to ventilation-induced lung injury.

METHODS: Sprague-Dawley rats were randomly exposed to a non-injurious low-stretch ventilation (V_T =9 ml/kg, PEEP=5 cm H₂O) (n=12) and an injurious high-stretch ventilation (V_T =25 ml/kg, PEEP=0 cm H₂O) (n=29). Animals were continuously monitored for a maximum period of 2.5 h. The high-stretch ventilation group (HV) was subdivided in two groups: 1) animals showing a substantial PO₂ reduction and peak airway pressure (Paw) increase, sacrificed at 60 min (HV60) (n=11); and 2) animals with insignificant PO₂ and Paw changes at 60 min (n=18), sacrificed at 150 min (HV150). Lung tissue, plasma, and bronchoalveolar fluid (BAL) were analyzed in the three groups. BAL provided native cytometric, inflammatory marker, and surfactant data.

RESULTS: The HV60 group was characterized by leakage of plasma proteins into the alveoli, presence of hyaline membranes, high increase of inflammatory markers in BAL (TNF-α, MIP-2, MCP-1, C-reactive protein, and acidic sphingomyelinase), pronounced decrease of alveolar macrophages, and an accelerated conversion of freshly secreted active surfactant to inactive surfactant. In contrast, the HV150 group was characterized by high amount of active surfactant, absence of edema, and normal PO₂. These animals exhibited a slight decrease of alveolar macrophages and increase of some BAL inflammatory markers (IL6, TNF-α, MIP-2, and MCP-1).

CONCLUSIONS: These results suggest that increased surfactant release into the alveolar space safeguards the lung from ventilation-induced injury and that surfactant alteration might directly contribute to lung dysfunction.