Abstract
Lung overstretch involves mechanical factors, including large tidal volumes (VT), which induce inflammatory responses. The current authors hypothesised that inspiratory flow contributes to ventilator-induced inflammation.
Buffer-perfused rabbit lungs were ventilated for 2 h with 21% O2+5% CO2, positive end-expiratory pressure of 2–3 cmH2O and randomly assigned to either: 1) normal VT (6 mL·kg−1) at respiratory rate (RR) 30, inspiration:expiration time ratio (I:E) 1:1, low inspiratory flow 6 mL·kg−1·s−1; 2) large VT (12 mL·kg−1) at RR 30, I:E 1:1, high inspiratory flow 12 mL·kg−1·s−1 (HRHF); 3) large VT at RR 15, I:E 1:1, low inspiratory flow 6 mL·kg−1·s−1 (LRLF); or 4) large VT at RR 15, I:E 1:2.3, high inspiratory flow 10 mL·kg−1·s−1 (LRHF). Physiological parameters, tumour necrosis factor (TNF)‐α, interleukin (IL)‐8 and activation of mitogen-activated protein kinases (extracellular signal-regulated kinase (ERK)1/2, p38 and stress-activated protein kinase (SAPK)/c‐Jun N‐terminal kinase (JNK)) were measured.
HRHF increased weight gain, perfusate IL‐8 and phosphorylation of ERK1/2, p38 and SAPK/JNK. These responses were absent during LRLF but present during LRHF. Changes in TNF‐α were small. Tissue IL‐8 and phospho‐ERK1/2 staining was localised primarily to smooth muscle, adventitia and bronchial epithelium within larger bronchioles and arterioles.
These results indicate that mild overstretch of perfused lungs during high inspiratory flow enhances inflammatory signalling by cells in lung regions most affected by strong turbulent airflow.
- acute lung injury
- inspiratory flow
- interleukin‐8
- mechanical ventilation
- mitogen-activated protein kinase
§These authors contributed equally to the study. The research described in this article has been reviewed by the Health Effects and Environmental Research Laboratory, United States Environmental Protection Agency and has been approved for publication. Approval does not signify that the contents necessarily reflect the views and policies of the Agency, nor does mention of the trade names or commercial products constitute endorsement or recommendation for use.
Footnotes
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