• Br J Anaesth · Apr 2005

    Reduced activation of immunomodulatory transcription factors during positive end-expiratory pressure adjustment based on volume-dependent compliance in isolated perfused rabbit lungs.

    • E A Kirchner, G Mols, G Hermle, J D Muehlschlegel, K K Geiger, J Guttmann, and H L Pahl.
    • Department of Anaesthesiology and Critical Care Medicine, University Hospital, Hugstetterstrasse 55, 79106 Freiburg, Germany. edgar.kirchner@uni-freiburg.de
    • Br J Anaesth. 2005 Apr 1;94(4):530-5.

    BackgroundRepeated alveolar collapse and cyclic alveolar overdistension with associated activation of inflammatory signalling cascades contribute to ventilator-induced lung injury (VILI). The appropriate positive end-expiratory pressure (PEEP) which prevents or ameliorates VILI is unknown. In the isolated perfused lung, repeated adjustments of PEEP based on the continuously analysed intratidal compliance-volume curve have previously been shown to result in full end-expiratory alveolar recruitment and low risk of cyclic alveolar overdistension. Accordingly, we tested the hypothesis that such ventilatory management reduces intrapulmonary activation of the immunomodulatory transcription factors nuclear factor kappaB (NF-kappaB), activator protein 1 (AP-1) and cAMP-responsive element binding protein (CREB) which induce the expression of various chemokines and cytokines.MethodsIsolated perfused rabbit lungs were randomly allocated to one of three groups: zero end-expiratory pressure (ZEEP) to induce repeated alveolar collapse (n=6), high PEEP to induce cyclic alveolar overdistension (n=6) and repeated PEEP adjustments based on intratidal compliance-volume curve analysis by the slice method to minimize repeated alveolar collapse and overdistension (n=9). All lungs were ventilated with a tidal volume of 6 ml kg(-1) bodyweight for 120 min. Thereafter, activation of transcription factors NF-kappaB, AP-1 and CREB in lung tissue was analysed by electrophoretic mobility shift assay.ResultsHigh PEEP was associated with the highest activation of NF-kappaB and AP-1 and repeated PEEP adjustments with the lowest activation when compared with the other two study groups (P<0.001). In contrast, activation of CREB did not differ between groups. Activated NF-kappaB and AP-1 protein complexes consisted mainly of the transactivators p50/p65 and c-Fos/Jun, respectively.ConclusionsIn isolated perfused rabbit lungs, repeated adjustments of PEEP based on the continuously analysed intratidal compliance-volume curve were associated with less activation of early steps of inflammatory signalling cascades than ventilation with ZEEP or high PEEP.

      Pubmed     Free full text   Copy Citation     Plaintext  

      Add institutional full text...

    Notes

     
    Knowledge, pearl, summary or comment to share?
    300 characters remaining
    help        
    You can also include formatting, links, images and footnotes in your notes
    • Simple formatting can be added to notes, such as *italics*, _underline_ or **bold**.
    • Superscript can be denoted by <sup>text</sup> and subscript <sub>text</sub>.
    • Numbered or bulleted lists can be created using either numbered lines 1. 2. 3., hyphens - or asterisks *.
    • Links can be included with: [my link to pubmed](http://pubmed.com)
    • Images can be included with: ![alt text](https://bestmedicaljournal.com/study_graph.jpg "Image Title Text")
    • For footnotes use [^1](This is a footnote.) inline.
    • Or use an inline reference [^1] to refer to a longer footnote elseweher in the document [^1]: This is a long footnote..

    hide…

What will the 'Medical Journal of You' look like?

Start your free 21 day trial now.

We guarantee your privacy. Your email address will not be shared.