TY - JOUR T1 - Intravenous sulforhodamine B reduces alveolar surface tension, improves oxygenation and reduces ventilation-induced lung injury in a respiratory distress model JF - bioRxiv DO - 10.1101/2020.04.08.031435 SP - 2020.04.08.031435 AU - You Wu AU - Tam L. Ngyuen AU - Carrie E. Perlman Y1 - 2020/01/01 UR - http://biorxiv.org/content/early/2020/04/09/2020.04.08.031435.1.abstract N2 - BACKGROUND In the neonatal (NRDS) and acute (ARDS) respiratory distress syndromes, mechanical ventilation supports gas exchange but can cause ventilation-induced lung injury (VILI). Also in NRDS and ARDS, surface tension, T, is elevated and VILI may be proportional to T. Surfactant therapy is effective in NRDS but not ARDS. Intravenous sulforhodamine B (SRB) administration is a potential alternative T-lowering therapy.METHODS In anesthetized rats, we injure the lungs with 15 min of 42 ml/kg tidal volume, VT, and zero end-expiratory pressure ventilation. Then, we lower VT to 6 ml/kg; apply positive end-expiratory pressure; and administer intravenous non-T-altering fluorescein (27 μM in plasma) without or with therapeutic SRB (10 nM in plasma). We increase inspired oxygen fraction, as necessary, to maintain >90% arterial oxygen saturation. After 4 hrs, we sacrifice the rat; sample systemic venous blood for injury marker ELISAs; excise the lungs; combine confocal microscopy and servo-nulling pressure measurement to determine T; image fluorescein in flooded alveoli to assess local permeability; and lavage the right middle lobe and quantify total protein content to assess global permeability.RESULTS Lungs exhibit focal injury. Surface tension is elevated 72% throughout control lungs and in uninjured regions of SRB-treated lungs, due to lack of recruitment maneuvers, but is normal in injured regions of treated lungs. Intravenous SRB marginally reduces global permeability at the expense of marginally increased local permeability, improves oxygenation and reduces injury markers.CONCLUSION Intravenous SRB reduces alveolar surface tension specifically in injured regions and holds promise as treatment for VILI.Summary In a model of respiratory distress, intravenously administered sulforhodamine B (SRB) crosses the injured alveolar-capillary barrier to reduce alveolar surface tension specifically in injured lung regions. This novel therapy improves oxygenation and reduces ventilation-induced lung injury. Intravenous SRB administration might help not-yet-ventilated respiratory distress patients avoid mechanical ventilation and ventilated respiratory distress patients survive.Competing Interest StatementThe authors have declared no competing interest. ER -