Sevoflurane does not restore alveolar fluid clearance in a murine model of endotoxin-induced acute lung injury.

Authors

Thomas Finotto, Baptiste Bezaud, Camille Theilliere, Coralie Roche, Lucie Vivier, Fanny Henrioux, Laurent Renard Triché, Cécile Saint-Béat, Louna Monturet, Corinne Belville, Damien Bouvier, Loic Blanchon, Vincent Sapin, Marc Garnier, Matthieu Jabaudon

Published in

Scientific reports. Jul 04, 2026. Epub Jul 04, 2026.

Abstract

Volatile anesthetics have demonstrated anti-inflammatory and epithelial-protective effects in several sterile experimental models of acute lung injury (ALI). However, their effects in endotoxin-induced ALI remain unclear, and recent clinical data have raised concerns regarding their potential impact on patient outcomes. We investigated whether sevoflurane restores alveolar fluid clearance (AFC) and preserves epithelial integrity in a murine model of lipopolysaccharide (LPS)-induced ALI. Wild-type (WT) and receptor for advanced glycation end-products-deficient (RAGE-/-) mice received intratracheal lipopolysaccharide (LPS) and were exposed to sevoflurane (1 vol %) or control gas for 1 h. Our primary outcome, the net AFC rate was measured 48 h after injury. Secondary outcomes included lung histology, bronchoalveolar lavage (BAL) protein and cytokine levels, and lung expression of epithelial sodium channel (ENaC), water transporter aquaporin-5 (AQP5), and adherens junction protein E-cadherin. LPS induced significant weight loss and severe lung injury, with impaired AFC and downregulation of ENaC and AQP5. Sevoflurane did not restore AFC, reduce alveolar-capillary permeability, or preserve epithelial junctional integrity. RAGE-/- mice exhibited attenuated lung injury and partial preservation of epithelial marker expression, without a statistically significant interaction with sevoflurane exposure. BAL cytokine levels were largely unaffected by sevoflurane. These findings suggest context-dependent effects of a 1-h exposure to 1.0 vol% sevoflurane in experimental ALI, with absence of epithelial benefit in a mouse model of endotoxin-induced ALI, in contrast with previously reported effects in a sterile model. This work may provide mechanistic insight into the differential translational impact of inhaled sedation strategies.

PMID:
42401636
Bibliographic data and abstract were imported from PubMed on 05 Jul 2026.

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