Apr 9, 2020

Intravenous sulforhodamine B reduces alveolar surface tension, improves oxygenation and reduces ventilation-induced lung injury in a respiratory distress model

BioRxiv : the Preprint Server for Biology
Y. WuCarrie E. Perlman


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 uM 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. ...Continue Reading

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