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

Abstract

In the neonatal (NRDS) and acute (ARDS) respiratory distress syndromes, 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, VT, and zero end-expiratory pressure ventilation. Then, over 4 hrs, we support the rats with protective ventilation - VT 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 mM 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 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 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), both 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. Sulforhodamine B administration improves oxygenation, reduces W/D and reduces plasma injury markers. Intravenous SRB holds promise as a therapy for respiratory distress.

Nanoparticle-mediated surfactant therapy in patients with severe COVID-19: a perspective

“…Hence, with nanoparticle-driven more efficient administration, the exogenous surfactant should work towards improved oxygenation, reduced systemic inflammation, and lower VILI as shown in live animal models. 37 Clinical studies have provided a strong rationale for employing exogenous surfactants in COVID-19 patients. 23,38 In a retrospective case-control pilot study conducted by Portman and colleagues, 23 seven COVID-19 PCR positive ARDS patients received liquid Curosurf (720 mg) in 150 ml normal saline through a bronchoscope into second-generation bronchi.…”