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In vivo and in vitro modelling in acute lung injury
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    S88 SOURCES OF INCREASED PLASMA SOLUBLE TNF RECEPTORS DURING INJURIOUS MECHANICAL VENTILATION IN MICE

    A. D. Dorr, M. R. Wilson, K. P. O’Dea, M. Takata. Department of Anaesthetics, Pain Medicine and Intensive Care, Imperial College, London, UK

    Introduction Increased plasma levels of soluble tumour necrosis factor (TNF) receptors (sTNFRs) are associated with mortality in patients with acute respiratory distress syndrome (ARDS) ventilated with high tidal volumes (VTs). These increases are considered to reflect either systemic inflammation, or decompartmentalisation of elevated intra-alveolar sTNFRs into the circulation due to alveolar–capillary barrier dysfunction. However, the contribution of mechanical ventilation per se has not been well defined. We have previously shown in an in vivo mouse model of pure ventilator-induced lung injury that sTNFRs can leak into the alveolar space from the plasma.1 Consequently, it is unclear where increases in plasma sTNFRs would originate.

    Methods Anaesthetised C57BL6 mice were ventilated with high (36–41 ml/kg) or low VT (8–9 ml/kg) for up to 2 h. Upon termination, plasma samples were taken for quantification of sTNFR p55 and p75 (ELISA), and lungs were harvested for flow cytometric analysis of lung cell suspensions for TNFR p55 and p75 expression.

    Results Plasma sTNFR p55 levels substantially increased at 1 h with high VT compared with low VT (see table 1), but declined at 2 h. A similar trend, though not statistically significant, was observed for sTNFR p75. After 2 h of high VT ventilation, pulmonary endothelial cells and lung-marginated monocytes had decreased surface expression of TNFRs. Lung-marginated neutrophils exhibited no changes in sTNFR expression.

    Conclusions These data indicate that injurious ventilation can induce systemic sTNFR changes in the absence of pre-existing lung/systemic pathology. The increases in plasma sTNFRs occur earlier than previously reported sTNFR elevation in the alveolar space,1 and therefore cannot be explained by decompartmentalisation of elevated intra-alveolar sTNFRs. Conversely, our data strongly …

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