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Liquid Lung Rest During Extracorporeal Life Support in a Porcine Model of Acute Lung Injury

Blauvelt, D.; Hesek, A.; Golecki, M.; Nithianadam, P.; Parrish, G. M.; Keith, J.; Jones, L.; Massa, K.; Weiss, S. L.; Shaffer, T.

2025-10-17 physiology
10.1101/2025.10.17.683108 bioRxiv
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RationaleIn patients with severe lung injury, extracorporeal life support can enable lung rest, but the optimal strategy is unknown. ObjectiveTo compare liquid lung rest versus standard gas rest ventilation in a porcine model of acute lung injury and extracorporeal life support. MethodsTwenty neonatal pigs with lung injury after systemic injection of oleic acid were placed on extracorporeal life support. Pigs were ventilated with standard rest settings (peak inspiratory pressure: 20 cmH2O; end expiratory pressure: 10 cmH2O; rate: 10 breaths/minute) and randomized to receive no additional therapy (gas ventilation) or 5 mL/kg perfluorooctylbromide instilled endotracheally (liquid lung rest). The study continued for 4 hours with hourly pulmonary compliance measurements. After euthanasia, lung samples were taken for histologic analysis. Inflammation was quantified via blood and lung tissue cytokines. Measurements and Main ResultsAll pigs achieved significant lung injury; static compliance decreased by a mean of 54%. After 4 hours of lung rest, static compliance was higher with liquid lung rest compared to gas ventilation (0.88{+/-}0.05 mL/kg/cmH2O versus 0.57{+/-}0.05, p<0.001). Histology revealed 2.1-fold greater airspace in dependent lung regions with liquid lung rest (p<0.001) and a reduced airspace heterogeneity index (LLR: 0.071{+/-}0.004, gas: 0.095{+/-}0.010, p=0.04), suggesting more uniform alveolar recruitment. Cytokine analysis demonstrated a 3.7-fold decrease in tissue interleukin-10 levels with liquid lung rest (p=0.02). ConclusionsLiquid lung rest improved pulmonary compliance, achieved better alveolar recruitment, and decreased tissue interleukin-10 levels compared to standard gas ventilation. This strategy may enhance lung recovery in acute lung injury requiring extracorporeal life support.

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