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Effects of a peripheral cholinesterase inhibitor on cytokine production and autonomic nervous activity in a rat model of sepsis.
MedLine Citation:
PMID:  22138106     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
PURPOSE: Recently, cholinergic anti-inflammatory pathway manipulation has been proposed as a new strategy to control cytokine production in sepsis. We investigated whether hypercytokinemia can be controlled via this pathway in an animal model of sepsis, with concomitant monitoring of autonomic nervous activity involving heart rate variability (HRV) analysis of electrocardiographic R-R intervals. METHODS: Sixty-eight adult male Sprague-Dawley rats were used (28 for examination of cytokine production and autonomic nervous activity; 40 for survival analysis). Each part of the study involved four animal groups, including two control groups without drug administration. Sepsis was induced by cecal ligation and puncture (CLP). Distigmine bromide, a peripheral, non-selective cholinesterase inhibitor (0.01mg/kg), was administered subcutaneously 90min after surgery. Continuous electrocardiograms were recorded for 5min before and after surgery (at intervals of 5h) in CLP and sham-operated animals for HRV analysis. Blood samples were collected 20h after surgery for serum cytokine and catecholamine assay. RESULTS: On HRV analysis, distigmine inhibited reduction of total power and high-frequency components in CLP animals (P<0.05). Distigmine significantly inhibited cytokine induction (IL-6 and IL-10) (P<0.01) as well as increase in serum levels of noradrenaline and dopamine (P<0.05). Distigmine did not significantly improve CLP animal survival rate. CONCLUSIONS: The cholinesterase inhibitor distigmine inhibited induction of inflammatory cytokines and catecholamines as well as HRV suppression in a rat CLP model, suggesting that an agent modulating the cholinergic anti-inflammatory pathway can control excess cytokine production involved in the pathogenesis of severe sepsis/septic shock.
Authors:
Daisuke Setoguchi; Henry Yatsuki; Tomohito Sadahiro; Masataka Nakamura; Yo Hirayama; Eizo Watanabe; Yoshihisa Tateishi; Shigeto Oda
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-12-2
Journal Detail:
Title:  Cytokine     Volume:  -     ISSN:  1096-0023     ISO Abbreviation:  -     Publication Date:  2011 Dec 
Date Detail:
Created Date:  2011-12-5     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9005353     Medline TA:  Cytokine     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2011 Elsevier Ltd. All rights reserved.
Affiliation:
Department of Emergency and Critical Care Medicine, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo, Chiba City, Chiba, Japan.
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