585 - Lung, Plasma, and Liver Crosstalk: Interplay of the organs following mechanical ventilation-induced lung injury

Poster Number: 585
Publication Number: 585.1523

Background: Proinflammatory mediators released into the systemic circulation of ventilated adults can initiate lung and liver dysfunction, and the lung immune landscape is mediated by hepatic signals during systemic inflammation. These interactions, however, remain enigmatic in ventilated preterm neonates.

Objective: The objective of this study is to elucidate the lung-liver axis in a preterm lamb model where lung-injury interactions have been described, using proteomics and bioinformatics to profile ventilator-induced changes in lung, liver, and plasma.

Design/Methods: 123-127d (term 145d) preterm lambs received 15-min respiratory support (initial dynamic PEEP manoeuvre) with either (i) no tidal inflations (P) (n=8) [DynPEEP], (ii) 20 cmH2O P (n=5) [Dyn20], or (iii) 30 cmH2O P (n=5) [Dyn30]; then 30-min apnoea for injury marker expression. Protein alterations in tissue and plasma were compared between DynPEEP and Dyn20 or Dyn30 with bioinformatic analysis performed to identify biological processes underlying proteome changes.

Results: Across sample types, principal component analysis revealed distinct clustering of Dyn20 and Dyn30 proteome from DynPEEP. In the lung, both Dyn20 and Dyn30 exhibited enrichment of proteins associated with immune regulation, coagulation, tissue remodelling, and metabolism. Alterations observed in the liver included increased inflammation, angiogenesis, and energy metabolism. Indicators of organ damage were significantly increased in Dyn30 plasma compared to DynPEEP and Dyn20, including antioxidative and anti-inflammatory proteins.

Conclusion(s): Extrapulmonary proteome changes were identified in the preterm liver and plasma following ventilation. Inflammatory, angiogenic, and metabolic processes upregulated in the liver indicate potential mechanisms driving hepatic dysfunction, and protein mediators of injury identified in plasma highlight their role in interorgan crosstalk.