Evolution of the inflammatory and fibroproliferative responses during resolution and repair after ventilator-induced lung injury in the rat

Gerard F. Curley, Maya Contreras, Brendan Higgins, Cecilia O'Kane, Daniel F. McAuley, Daniel O'Toole, John G. Laffey*

*Corresponding author for this work

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Background: The time course and mechanisms of resolution and repair, and the potential for fibrosis following ventilation-induced lung injury (VILI), are unclear. We sought to examine the pattern of inflammation, injury, repair, and fibrosis following VILI. Methods: Sixty anesthetized rats were subject to high-stretch; low-stretch, or sham ventilation, and randomly allocated to undergo periods of recovery of 6, 24, 48, and 96 h, and 7 and 14 days. Animals were then reanesthetized, and the extent of lung injury, inflammation, and repair determined. RESULTS:: No injury was seen following low-stretch or sham ventilation. VILI caused severe lung injury, maximal at 24 h, but largely resolved by 96 h. Arterial oxygen tension decreased from a mean (SD) of 144.8 (4.1) mmHg to 96.2 (10.3) mmHg 6 h after VILI, before gradually recovering to 131.2 (14.3) mmHg at 96 h. VILI induced an early neutrophilic alveolitis and a later lymphocytic alveolitis, followed by a monocyte/macrophage infiltration. Alveolar tumor necrosis factor-α, interleukin-1β, and transforming growth factor-β1 concentrations peaked at 6 h and returned to baseline within 24 h, while interleukin-10 remained increased for 48 h. VILI generated a marked but transient fibroproliferative response, which restored normal lung architecture. There was no evidence of fibrosis at 7 and 14 days. Conclusions: High-stretch ventilation caused severe lung injury, activating a transient inflammatory and fibroproliferative repair response, which restored normal lung architecture without evidence of fibrosis.

Original languageEnglish
Pages (from-to)1022-1032
Number of pages11
JournalAnesthesiology
Volume115
Issue number5
DOIs
Publication statusPublished - Nov 2011

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine

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