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Proteomics reveals region-specific hemostatic alterations in response to mechanical ventilation in a preterm lamb model of lung injury.

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 H2O, 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.

journal_name

Thromb Res

journal_title

Thrombosis research

authors

Schmid C,Ignjatovic V,Pang B,Nie S,Williamson NA,Tingay DG,Pereira-Fantini PM

doi

10.1016/j.thromres.2020.09.036

subject

Has Abstract

pub_date

2020-12-01 00:00:00

pages

466-475

eissn

0049-3848

issn

1879-2472

pii

S0049-3848(20)30545-4

journal_volume

196

pub_type

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Proteomics reveals region-specific hemostatic alterations in response to mechanical ventilation in a preterm lamb model of lung injury.