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Sepsis-associated changes of the arachidonic acid metabolism and their diagnostic potential in septic patients*.
MedLine Citation:
PMID:  22511130     Owner:  NLM     Status:  In-Data-Review    
OBJECTIVES: : Sepsis-associated changes of the arachidonic acid metabolism and the utility of arachidonic acid metabolites for the diagnosis of sepsis have been poorly investigated so far. Therefore, the primary objective of our study was to screen for differentially regulated arachidonic acid metabolites in septic patients using a lipopolysaccharide whole-blood model and to investigate their diagnostic potential.
DESIGN: : Prospective, observational, single-center, clinical study.
SETTING: : Intensive care unit at University Hospital Leipzig.
PATIENTS: : Thirty-five patients (first cohort 25 patients, second cohort 10 patients) meeting the criteria for severe sepsis or septic shock were enrolled. Eighteen healthy volunteers (first cohort 15 subjects, second cohort 3 subjects) were enrolled as controls.
MEASUREMENTS AND MAIN RESULTS: : Arachidonic acid and its metabolites were investigated in supernatants of nonactivated (baseline) and lipopolysaccharide-activated heparinized whole blood of healthy subjects (n = 15) and septic patients (n = 25) by solid phase extraction and subsequent liquid chromatography-tandem mass spectrometry. Arachidonic acid, arachidonic acid analogues, and the cyclooxygenase-associated metabolites prostaglandin E2, 11-hydroxyeicosatetraenoic acid, and thromboxane B2 were identified as differentiating metabolites between septic patients and healthy subjects. Some of these compounds, including arachidonic acid, its analogues, and the cyclooxygenase metabolites prostaglandin E2 and thromboxane B2 differed at baseline. The inducibility of arachidonic acid and the cyclooxygenase metabolites 11-hydroxyeicosatetraenoic and prostaglandin E2 were reduced by 80% to 90% in septic patients. The degree of the inducibility was associated with severity of sepsis and clinical outcome. A reduced inducibility of COX-2 but preserved inducibility of mPGES-1 on gene expression level were confirmed in an independent cohort of septic patients (n = 10) by quantitative reverse-transcription polymerase chain reaction compared to healthy controls (n = 3).
CONCLUSIONS: : Arachidonic acid metabolism is markedly affected in patients with sepsis. Our data suggest that the analysis of arachidonic acid metabolites in an in vitro whole blood activation model may be a promising approach for risk estimation in septic patients that has to be further evaluated in subsequent large-scale clinical studies.
Mathias Bruegel; Ute Ludwig; Alisa Kleinhempel; Sirak Petros; Linda Kortz; Uta Ceglarek; Lesca Miriam Holdt; Joachim Thiery; Georg Martin Fiedler
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Critical care medicine     Volume:  40     ISSN:  1530-0293     ISO Abbreviation:  Crit. Care Med.     Publication Date:  2012 May 
Date Detail:
Created Date:  2012-04-18     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0355501     Medline TA:  Crit Care Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1478-86     Citation Subset:  AIM; IM    
From the Institute of Laboratory Medicine (MB, UT, AK, LK, UC, MH, JT, GMF), Clinical Chemistry and Molecular Diagnostics, University Hospital Leipzig, Leipzig; Department of Internal Medicine (SP), Intensive Care Unit, University Hospital Leipzig, Leipzig; Leipzig Interdisciplinary Research Cluster of Genetic Factors (LK, UC, MH, JT), Clinical Phenotypes and Environment, Leipzig, Germany.
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