Document Detail

Pharmacologic stimulation of the nicotinic anti-inflammatory pathway modulates gut and lung injury after hypoxia-reoxygenation injury.
MedLine Citation:
PMID:  24074423     Owner:  NLM     Status:  In-Data-Review    
PURPOSE: Pre-injury vagal nerve stimulation protects against gut and lung injury after experimental hemorrhagic shock (HS). This likely occurs via the cholinergic anti-inflammatory pathway and the α7 nicotinic acetylcholine receptor (α7nAChR). We hypothesized that, in an in vitro model, either nicotine or a selective α7nAChR agonist (AR-R17779) would modulate intestinal and pulmonary effects of gut ischemia-reperfusion after hypoxic insult.
METHODS: Confluent HT29 intestinal epithelial cells were co-cultured with Escherichia coli. Cell cultures were subjected to 21% (control) or 5% O2 (hypoxia) for 90 minutes followed by reoxygenation (H/R). HT29 cells were treated with nicotine or AR-R17779 before or immediately after hypoxic insult. From the HT29 cell culture supernatants, tumor necrosis factor-α and interleukin-6 levels were quantitated. Confluent pulmonary microvascular epithelial cells (HMVEC) were co-cultured with HT29 supernatants and permeability and intercellular adhesion molecule-1 expression were determined.
RESULTS: In post H/R insult treatments with the receptor agonist, cytokine levels in HT29 cells were reduced to control levels. In HMVEC experiments, a protective effect was seen with treatment post H/R injury. Disruption of HT29 actin microfilaments was demonstrated after H/R insult and was abrogated by both agonists.
CONCLUSION: Post-insult pharmacologic stimulation seems to mimic the protective effects of pre-HS vagal nerve stimulation seen in animal studies.
Samantha L Tarras; Lawrence N Diebel; David M Liberati; Kevin Ginnebaugh
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Surgery     Volume:  154     ISSN:  1532-7361     ISO Abbreviation:  Surgery     Publication Date:  2013 Oct 
Date Detail:
Created Date:  2013-09-30     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0417347     Medline TA:  Surgery     Country:  United States    
Other Details:
Languages:  eng     Pagination:  841-8     Citation Subset:  AIM; IM    
Copyright Information:
Copyright © 2013 Mosby, Inc. All rights reserved.
Department of Surgery, Wayne State University, Detroit, MI.
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