Proteomics reveals region-specific hemostatic alterations in response to mechanical ventilation in a preterm lamb model of lung injury. Issue 196 (December 2020)

• Record Type: Journal Article
• Authors: Schmid, Christine; Ignjatovic, Vera; Pang, Boyuan; Nie, Shuai; Williamson, Nicholas A.; Tingay, David G.; Pereira-Fantini, Prue M.
• Is Part Of: Thrombosis research. Issue 196(2020)
• Page Start: 466
• Page End: 475
• Publication Date: 2020-12
• Subjects: CPAP continuous positive airway pressure -- CoV geometric centre of gravity-dependent ventilation -- DMSO dimethyl sulfoxide -- EIT electrical impedance tomography -- FA formic acid -- FC fold change -- IM intramuscular -- IV intravenous -- KEGG Kyoto Encyclopedia of Genes and Genomes -- MS mass spectrometry -- PEEP positive end-expiratory pressure -- PIP peak inspiratory pressure -- PPV positive pressure ventilation -- RDS respiratory distress syndrome -- UVC unventilated control -- VILI ventilator-induced lung injury -- VT tidal volume; Preterm -- Lung injury -- Coagulation -- Platelet activation -- Proteomics; Thrombosis -- Periodicals; 616.135
• DOI: 10.1016/j.thromres.2020.09.036
• Languages: English
• ISSNs: 0049-3848

Abstract

Abstract: Introduction: Preterm infants often require assisted ventilation, however ventilation when applied to the immature lung can initiate ventilator-induced lung injury (VILI). The biotrauma which underscores VILI is largely undefined, and is likely to involve vascular injury responses, including hemostasis. We aimed to use a ventilated, preterm lamb model to: (1) characterize regional alterations in hemostatic mediators within the lung and (2) assess the functional impact of protein alterations on hemostasis by analyzing temporal thrombin generation. Materials and methods: Preterm lambs delivered at 124 to 127 days gestation received 90 min of mechanical ventilation (positive end-expiratory pressure = 8 cm H2 O, VT = 6–8 ml/kg) and were compared with unventilated control lambs. At study completion, lung tissue was taken from standardized nondependent and gravity-dependent regions, and Orbitrap-mass spectrometry and KEGG were used to identify and map regional alterations in hemostasis pathway members. Temporal alterations in plasma thrombin generation were assessed. Results: Ventilation was distributed towards the nondependent lung. Significant changes in hemostatic protein abundance, were detected at a two-fold higher rate in the nondependent lung when compared with the gravity-dependent lung. Seven proteins were uniquely altered in non-dependent lung (SERPINA1, MYL12A, RAP1B, RHOA, ITGB1, A2M, GNAI2), compared with a single proteins in gravity-dependent lung (COL1A2). Four proteins were altered in both regions (VTN, FGG, FGA, and ACTB). Tissue protein alterations were mirrored by plasma hypocoagulability at 90-minutes of ventilation. Conclusions: We observed regionally specific, hemostatic alterations within the preterm lung together with disturbed fibrinolysis following a short period of mechanical ventilation. Highlights: Short periods of ventilation resulted in regional disturbances in hemostasis. A greater magnitude of hemostatic disturbance is observed in the non-dependent lung. Tissue proteome alterations predominantly reflected disturbed fibrinolysis. Tissue protein alterations were mirrored by plasma hypocoaguability.