| Abstract |
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. Summary In the acute respiratory distress syndrome (ARDS), surface tension, T, is believed to be elevated and surfactant therapy has failed to reduce mortality. Here, we test whether various substances suggested to contribute to elevated T in ARDS in fact raise T in the lungs. And we test the ability of exogenous surfactant and of a potential alternative therapeutic, sulforhodamine B (SRB), to reduce T. We find exogenous surfactant unable to lower T in the presence of cell debris but SRB, which can be administered intravascularly, a candidate for lowering T in non-aspiration ARDS.
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