Document Detail


Evaluation of asymmetric dimethylarginine, arginine, and carnitine metabolism in pediatric sepsis.
MedLine Citation:
PMID:  22460770     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: Increased plasma concentrations of the endogenous nitric oxide synthase inhibitor, asymmetric dimethylarginine, decreased arginine bioavailability, and mitochondrial dysfunction have been reported in adult sepsis. We studied whether asymmetric dimethylarginine, arginine, and carnitine metabolism (a measure of mitochondrial dysfunction) are altered in pediatric sepsis and whether these are clinically useful biomarkers.
DESIGN: : Prospective, observational study.
SETTING: Pediatric intensive care unit at an academic medical center.
PATIENTS: : Ninety patients ≤ 18 yrs old, 30 with severe sepsis or septic shock, compared with 30 age-matched febrile and 30 age-matched healthy control subjects.
INTERVENTIONS: None.
MEASUREMENTS AND MAIN RESULTS: Plasma asymmetric dimethylarginine and whole blood arginine, citrulline, ornithine, and acylcarnitine:free carnitine ratio were measured daily for septic patients and once for control subjects using tandem mass spectrometry. Plasma asymmetric dimethylarginine concentration (median; interquartile range µmol/L) on day 1 was lower in severe sepsis and septic shock (0.38; 0.30-0.56) compared with febrile (0.45; 0.40-0.59) and healthy (0.60; 0.54-0.67) control subjects (p < .001), although decreased asymmetric dimethylarginine was predominantly found in neutropenic patients. Day 1 arginine was lower in septic (10; interquartile range, 7-20 µmol/L) compared with healthy patients (32; interquartile range, 23-40; p < .001), and the arginine:ornithine ratio was decreased in sepsis, indicating increased arginase activity (an alternative pathway for arginine metabolism). The arginine:asymmetric dimethylarginine and acylcarnitine:free carnitine ratios did not differ between septic and control patients. Asymmetric dimethylarginine was inversely correlated with organ dysfunction by Pediatric Logistic Organ Dysfunction score (r = -0.50, p = .009), interleukin-6 (r = -0.55, p = .01), and interleukin-8 (r = -0.52, p = .03) on admission. Arginine, arginine:asymmetric dimethylarginine, and acylcarnitine:free carnitine were not associated with organ dysfunction or outcomes.
CONCLUSIONS: Asymmetric dimethylarginine was decreased in pediatric sepsis and was inversely associated with inflammation and organ dysfunction. This suggests that inhibition of nitric oxide synthase by asymmetric dimethylarginine accumulation is unlikely to impact sepsis pathophysiology in septic children despite decreased arginine bioavailability. We did not find an association of asymmetric dimethylarginine with altered carnitine metabolism nor were asymmetric dimethylarginine, arginine, and acylcarnitine:free carnitine useful as clinical biomarkers.
Authors:
Scott L Weiss; Shannon Haymond; Hantamalala Ralay Ranaivo; Deli Wang; Victor R De Jesus; Donald H Chace; Mark S Wainwright
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies     Volume:  13     ISSN:  1529-7535     ISO Abbreviation:  Pediatr Crit Care Med     Publication Date:  2012 Jul 
Date Detail:
Created Date:  2012-07-09     Completed Date:  2012-11-21     Revised Date:  2013-07-03    
Medline Journal Info:
Nlm Unique ID:  100954653     Medline TA:  Pediatr Crit Care Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  e210-8     Citation Subset:  IM    
Affiliation:
Divisions of Critical Care, Children's Memorial Hospital, Northwestern Feinberg School of Medicine, Chicago, IL, USA.
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MeSH Terms
Descriptor/Qualifier:
Adolescent
Arginine / analogs & derivatives*,  blood*
Carnitine / blood*
Case-Control Studies
Child
Child, Preschool
Enzyme-Linked Immunosorbent Assay
Female
Humans
Male
Prospective Studies
Sepsis / blood*
Grant Support
ID/Acronym/Agency:
UL1 RR025741-01/RR/NCRR NIH HHS; UL1RR025741/RR/NCRR NIH HHS
Chemical
Reg. No./Substance:
30315-93-6/N,N-dimethylarginine; 541-15-1/Carnitine; 74-79-3/Arginine
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