title: Imbalance of arginine and asymmetric dimethylarginine is associated with markers of circulatory failure, organ failure and mortality in shock patients.
abstract: In shock, organ perfusion is of vital importance because organ oxygenation is at risk. NO, the main endothelial-derived vasodilator, is crucial for organ perfusion and coronary patency. The availability of NO might depend on the balance between a substrate (arginine) and an inhibitor (asymmetric dimethylarginine; ADMA) of NO synthase. Therefore, we investigated the relationship of arginine, ADMA and their ratio with circulatory markers, disease severity, organ failure and mortality in shock patients. In forty-four patients with shock (cardiogenic n 17, septic n 27), we prospectively measured plasma arginine and ADMA at intensive care unit admission, Acute Physiology and Chronic Health Evaluation (APACHE) II-(predicted mortality) and Sequential Organ Failure Assessment (SOFA) score, and circulatory markers to investigate their relationship. Arginine concentration was decreased (34·6 (SD 17·9) μmol/l) while ADMA concentration was within the normal range (0·46 (SD 0·18) μmol/l), resulting in a decrease in the arginine:ADMA ratio. The ratio correlated with several circulatory markers (cardiac index, disseminated intravascular coagulation, bicarbonate, lactate and pH), APACHE II and SOFA score, creatine kinase and glucose. The arginine:ADMA ratio showed an association (OR 0·976, 95 % CI 0·963, 0·997, P = 0·025) and a diagnostic accuracy (area under the curve 0·721, 95 % CI 0·560, 0·882, P = 0·016) for hospital mortality, whereas the arginine or ADMA concentration alone or APACHE II-predicted mortality failed to do so. In conclusion, in shock patients, the imbalance of arginine and ADMA is related to circulatory failure, organ failure and disease severity, and predicts mortality. We propose a pathophysiological mechanism in shock: the imbalance of arginine and ADMA contributes to endothelial and cardiac dysfunction resulting in poor organ perfusion and organ failure, thereby increasing the risk of death.
authors: Department of Surgery, VU University Medical Center, PO Box 7057, 1007 MB Amsterdam, The Netherlands.
authors: Marlieke
authors: M
authors: Visser
authors: Mechteld A R
authors: MA
authors: Vermeulen
authors: Milan C
authors: MC
authors: Richir
authors: Tom
authors: T
authors: Teerlink
authors: Alexander P J
authors: AP
authors: Houdijk
authors: Piet J
authors: PJ
authors: Kostense
authors: Willem
authors: W
authors: Wisselink
authors: Bas A J M
authors: BA
authors: de Mol
authors: Paul A M
authors: PA
authors: van Leeuwen
authors: Heleen M
authors: HM
authors: Oudemans-van Straaten
mesh_terms: D000368:Aged; D019540:Area Under Curve; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood*; D015415:Biomarkers / Q000097:blood*; D001777:Blood Coagulation; D001786:Blood Glucose / Q000378:metabolism; D002254:Carbonates / Q000097:blood; D003402:Creatine Kinase / Q000097:blood; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration; D019344:Lactic Acid / Q000097:blood; D008297:Male; D008875:Middle Aged; D009102:Multiple Organ Failure / Q000097:blood* / Q000401:mortality; D009569:Nitric Oxide / Q000097:blood; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012720:Severity of Illness Index; D012769:Shock / Q000097:blood* / Q000401:mortality
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D002254:Carbonates; D009569:Nitric Oxide; D019344:Lactic Acid; C018524:N,N-dimethylarginine; D001120:Arginine; D019001:Nitric Oxide Synthase; D003402:Creatine Kinase