Document Detail


Metabolic profiling of arginine and nitric oxide pathways predicts hemodynamic abnormalities and mortality in patients with cardiogenic shock after acute myocardial infarction.
MedLine Citation:
PMID:  17967979     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: It is unclear whether abnormalities of arginine and nitric oxide metabolism are related to hemodynamic dysfunction and mortality in patients with cardiogenic shock (CS) after acute myocardial infarction. METHODS AND RESULTS: Plasma metabolites reflecting arginine bioavailability, nitric oxide metabolism, and protein oxidation were analyzed by mass spectrometry in patients with CS (n=79) and age- and gender-matched patients with coronary artery disease and normal left ventricular function (n=79). CS patients had higher levels of asymmetric dimethylarginine (ADMA; P<0.0001), symmetric dimethylarginine (P<0.0001), monomethylarginine (P=0.0003), nitrotyrosine (P<0.0001), and bromotyrosine (P<0.0001) and lower levels of arginine (P<0.0001), ratio of arginine to ornithine (P=0.03), and ratio of arginine to ornithine plus citrulline) (P=0.0003). CS patients with elevated ADMA levels were 3.5-fold (95% confidence interval, 1.4 to 11.3; P=0.02) more likely to die in 30 days than patients with low ADMA levels. ADMA remained the only independent predictor of mortality on multiple logistic regression analysis. In patients with normal renal function, symmetric dimethylarginine levels inversely correlated with mean arterial pressure and systemic vascular resistance, whereas levels of ADMA correlated with pulmonary capillary wedge pressure and both systolic and diastolic pulmonary artery pressures. Despite dramatic elevations, levels of protein oxidation products did not predict hemodynamic dysfunction or mortality in CS patients. CONCLUSIONS: CS is characterized by an arginine-deficient and highly specific pro-oxidant state, with elevated levels of methylated arginine derivatives, including endogenous nitric oxide synthase inhibitors. Levels of methylated arginine derivatives strongly correlate with hemodynamic dysfunction. Among all clinical and laboratory parameters monitored, ADMA levels were the strongest independent predictor of 30-day mortality.
Authors:
Stephen J Nicholls; Zeneng Wang; Robert Koeth; Bruce Levison; Brian DelFraino; Vladimir Dzavik; Owen W Griffith; David Hathaway; Julio A Panza; Steven E Nissen; Judith S Hochman; Stanley L Hazen
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2007-10-29
Journal Detail:
Title:  Circulation     Volume:  116     ISSN:  1524-4539     ISO Abbreviation:  Circulation     Publication Date:  2007 Nov 
Date Detail:
Created Date:  2007-11-13     Completed Date:  2007-12-18     Revised Date:  2008-09-23    
Medline Journal Info:
Nlm Unique ID:  0147763     Medline TA:  Circulation     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2315-24     Citation Subset:  AIM; IM    
Affiliation:
Department of Cardiovascular Medicine and Center for Cardiovascular Diagnostics and Prevention, Cleveland Clinic Foundation, 9500 Euclid Ave, NE-10, Cleveland, OH 44195, USA. nichols1@ccf.org
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MeSH Terms
Descriptor/Qualifier:
Aged
Arginine / metabolism*
Biological Markers
Citrulline / metabolism
Humans
Male
Methylation
Myocardial Infarction / metabolism*,  mortality*
Nitric Oxide / metabolism*
Ornithine / metabolism
Oxidation-Reduction
Oxidative Stress
Predictive Value of Tests
Shock, Cardiogenic / metabolism*,  mortality*
Grant Support
ID/Acronym/Agency:
HL081064/HL/NHLBI NIH HHS; HL70621/HL/NHLBI NIH HHS; M01 RR018390/RR/NCRR NIH HHS; P01 HL076491/HL/NHLBI NIH HHS; P01 HL77107/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Biological Markers; 10102-43-9/Nitric Oxide; 372-75-8/Citrulline; 7006-33-9/Ornithine; 74-79-3/Arginine
Comments/Corrections
Comment In:
Circulation. 2008 Sep 2;118(10):e149; author reply e150   [PMID:  18765383 ]

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