Sulforhodamine B and exogenous surfactant effects on alveolar surface tension in acute respiratory distress syndrome models

BACKGROUND: In the acute respiratory distress syndrome (ARDS), elevated alveolar surface tension, T, may increase ventilation-induced lung injury. Exogenous surfactant therapy has not reduced ARDS mortality. Sulforhodamine B (SRB), which acts with albumin to improve native lung surfactant efficacy, could be an alternative T-lowering therapeutic. We test whether substances suspected of elevating T in ARDS raise T in the lungs - where, unlike in most in vitro tests, the surfactant monolayer is intact - and test the abilities of exogenous surfactant and SRB to reduce T. METHODS: In isolated rat lungs, we micropuncture a surface alveolus and instill a solution containing a substance purported to raise T in ARDS: control saline, cell debris, secretory phospholipase A2 (sPLA2), acid or mucins. We test each substance alone; with albumin, to model proteinaceous edema liquid; with albumin and subsequent exogenous surfactant; or with albumin and SRB. We determine T by combining servo-nulling pressure measurement with confocal microscopy, and applying the Laplace relation. RESULTS: In the control group, saline, albumin and Infasurf do not alter T; SRB reduces T below normal. With albumin, the experimental substances raise T. With cell debris, surfactant does not alter T; SRB normalizes T. With sPLA2, surfactant normalizes T; SRB reduces T. With acid or mucins, neither surfactant nor SRB alters T. CONCLUSIONS: The inability of surfactant to counter cell debris may contribute to the failure of surfactant therapy for ARDS. For non-aspiration ARDS, SRB, which can be delivered intravascularly to target injured lung regions, holds promise as a treatment.