Open AccessIntravenous sulforhodamine B reduces alveolar surface tension, improves oxygenation, and reduces ventilation injury in a respiratory distress model
Author(s) -
You Wu,
Tam Luong Nguyen,
Carrie E. Perlman
Publication year - 2021
Publication title -
journal of applied physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.253
H-Index - 229
eISSN - 8750-7587
pISSN - 1522-1601
DOI - 10.1152/japplphysiol.00421.2020
Subject(s) - ards , medicine , anesthesia , oxygenation , lung , mechanical ventilation , oxygen tension , respiratory distress , diffuse alveolar damage , ventilation (architecture) , tidal volume , respiratory system , pulmonary surfactant , chemistry , acute respiratory distress , oxygen , mechanical engineering , biochemistry , engineering , organic chemistry
In the neonatal respiratory distress syndrome (NRDS) and acute respiratory distress syndrome (ARDS), mechanical ventilation supports gas exchange but can cause ventilation-induced lung injury (VILI) that contributes to high mortality. Further, surface tension, T , should be elevated and VILI is proportional to T . Surfactant therapy is effective in NRDS but not ARDS. Sulforhodamine B (SRB) is a potential alternative T- lowering therapeutic. In anesthetized male rats, we injure the lungs with 15 min of 42 mL/kg tidal volume, V T , and zero end-expiratory pressure ventilation. Then, over 4 h, we support the rats with protective ventilation- V T of 6 mL/kg with positive end-expiratory pressure. At the start of the support period, we administer intravenous non- T -altering fluorescein (targeting 27 µM in plasma) without or with therapeutic SRB (10 nM). Throughout the support period, we increase inspired oxygen fraction, as necessary, to maintain >90% arterial oxygen saturation. At the end of the support period, we euthanize the rat; sample systemic venous blood for injury marker ELISAs; excise the lungs; combine confocal microscopy and servo-nulling pressure measurement to determine T in situ in the lungs; image fluorescein in alveolar liquid to assess local permeability; and determine lavage protein content and wet-to-dry ratio ( W / D ) to assess global permeability. Lungs exhibit focal injury. Surface tension is elevated 72% throughout control lungs and in uninjured regions of SRB-treated lungs, but normal in injured regions of treated lungs. SRB administration improves oxygenation, reduces W / D , and reduces plasma injury markers. Intravenous SRB holds promise as a therapy for respiratory distress. NEW & NOTEWORTHY Sulforhodmaine B lowers T in alveolar edema liquid. Given the problematic intratracheal delivery of surfactant therapy for ARDS, intravenous SRB might constitute an alternative therapeutic. In a lung injury model, we find that intravenously administered SRB crosses the injured alveolar-capillary barrier thus reduces T specifically in injured lung regions; improves oxygenation; and reduces the degree of further lung injury. Intravenous SRB administration might help respiratory distress patients, including those with the novel coronavirus, avoid mechanical ventilation or, once ventilated, survive.