Document Detail

Reduced activation of immunomodulatory transcription factors during positive end-expiratory pressure adjustment based on volume-dependent compliance in isolated perfused rabbit lungs.
MedLine Citation:
PMID:  15665073     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: Repeated 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.
METHODS: Isolated 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.
RESULTS: High 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.
CONCLUSIONS: In 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.
E A Kirchner; G Mols; G Hermle; J D Muehlschlegel; K K Geiger; J Guttmann; H L Pahl
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Publication Detail:
Type:  Journal Article     Date:  2005-01-21
Journal Detail:
Title:  British journal of anaesthesia     Volume:  94     ISSN:  0007-0912     ISO Abbreviation:  Br J Anaesth     Publication Date:  2005 Apr 
Date Detail:
Created Date:  2005-03-10     Completed Date:  2005-04-26     Revised Date:  2014-07-11    
Medline Journal Info:
Nlm Unique ID:  0372541     Medline TA:  Br J Anaesth     Country:  England    
Other Details:
Languages:  eng     Pagination:  530-5     Citation Subset:  IM    
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MeSH Terms
Cyclic AMP Response Element Modulator
DNA-Binding Proteins / metabolism
Electrophoretic Mobility Shift Assay
Lung / immunology,  metabolism
Lung Compliance / physiology*
NF-kappa B / metabolism
Positive-Pressure Respiration / methods*
Respiratory Mechanics / physiology
Tidal Volume
Transcription Factor AP-1 / metabolism
Transcription Factors / metabolism*
Reg. No./Substance:
0/DNA-Binding Proteins; 0/NF-kappa B; 0/Transcription Factor AP-1; 0/Transcription Factors; 135844-64-3/Cyclic AMP Response Element Modulator

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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