Impact of tidal volume strategy at birth on initiating lung injury in preterm lambs.

Abstract

Tidal ventilation is essential in supporting the transition to air-breathing at birth, but excessive tidal volume (VT) is an important factor in preterm lung injury. Few studies have assessed the impact of specific VT levels on injury development. Here we used a lamb model of preterm birth to investigate the role of different levels of VT during positive pressure ventilation (PPV) in promoting aeration and initiating early lung injury pathways. VT was delivered as; (i) 7ml/kg throughout (VTstatic), (ii) begun at 3ml/kg and increased to a final VT of 7ml/kg over 3-minutes (VTinc) or (iii) commenced at 7ml/kg, decreased to 3ml/kg and the returned to 7ml/kg (VTalt). VT, inflating pressure, lung compliance and aeration were similar in all groups from 4 minutes, as was post-mortem histology and lung lavage protein concentration. However, transient decrease in VT in the VTalt group caused increased ventilation heterogeneity. Following TMT-based quantitative mass spectrometry proteomics, 1610 proteins were identified in the lung. 3-fold more proteins were significantly altered with VTalt compared with VTstatic or VTinc strategies. Gene set enrichment analysis identified VTalt specific enrichment of immune and angiogenesis pathways and VTstatic enrichment of metabolic processes. Our finding of comparable lung physiology and volutrauma across VT groups challenges the paradigm that there is a need to rapidly aerate the preterm lung at birth. Increased lung injury and ventilation heterogeneity was identified when initial VT was suddenly decreased during respiratory support at birth, further supporting the benefit of a gentle VT approach.