Document Detail


Tryptophan metabolism to kynurenine is a potential novel contributor to hypotension in human sepsis.
MedLine Citation:
PMID:  21765346     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
OBJECTIVES:: To determine whether tryptophan metabolism to kynurenine contributes to the direct regulation of vascular tone in human septic shock. BACKGROUND:: Indoleamine 2,3-dioxygenase 1 is an inducible enzyme that converts tryptophan to kynurenine and shares functional similarities with inducible nitric oxide synthase. Recently, kynurenine has been identified as an endothelium-derived relaxing factor produced during inflammation, raising the possibility that this novel pathway may contribute to hypotension in human sepsis. DESIGN:: Prospective, matched, single-center, cohort study. SETTINGS:: Intensive care unit of a tertiary teaching hospital matched to control subjects from the general medical ward and healthy volunteers. SUBJECTS:: Patients (n = 16) with septic shock had indoleamine 2,3-dioxygenase 1 activity assessed as the kynurenine-to-tryptophan ratio, and the severity of hypotension was determined by their inotrope requirements. Healthy and blood pressure-matched nonseptic control subjects were also studied. INTERVENTIONS:: None. MEASUREMENTS AND MAIN RESULTS:: Tissues from septic and control patients were stained for the presence of indoleamine 2,3-dioxygenase 1. Indoleamine 2,3-dioxygenase 1 activity increased up to ninefold in patients with septic shock and was significantly higher than in the two control groups (p < .005). Indoleamine 2,3-dioxygenase 1 activity was strongly correlated with inotrope requirements (p < .001). Indoleamine 2,3-dioxygenase 1 protein was expressed in inflamed cardiac tissue as well as in endothelial cells of resistance vessels in hearts and kidneys from subjects who died from sepsis. CONCLUSIONS:: Indoleamine 2,3-dioxygenase 1 is expressed in resistance vessels in human sepsis and Indoleamine 2,3-dioxygenase 1 activity correlates with hypotension in human septic shock. Indoleamine 2,3-dioxygenase 1 is thus a potential novel contributor to hypotension in sepsis.
Authors:
Dechaboon Changsirivathanathamrong; Yutang Wang; Dorrilyn Rajbhandari; Ghassan J Maghzal; Wendy M Mak; Clive Woolfe; Johan Duflou; Val Gebski; Cris G Dos Remedios; David S Celermajer; Roland Stocker
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-7-14
Journal Detail:
Title:  Critical care medicine     Volume:  -     ISSN:  1530-0293     ISO Abbreviation:  -     Publication Date:  2011 Jul 
Date Detail:
Created Date:  2011-7-18     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0355501     Medline TA:  Crit Care Med     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
From the Centre for Vascular Research (DC, YW, GJM, WMM, RS), School of Medical Sciences (Pathology) and Bosch Institute, Sydney, Australia; Royal Prince Alfred Hospital (DC, DR, CW, DSC), Sydney, Australia; the Department of Forensic Medicine Sydney (JD), Sydney, Australia; NHMRC Clinical Trials Centre (VG), Sydney, Australia; and the School of Medical Sciences (Anatomy) and Bosch Institute (CGdR), The University of Sydney, Sydney NSW, Australia.
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