TY - JOUR
T1 - Imbalance of arginine and asymmetric dimethylarginine is associated with markers of circulatory failure, organ failure and mortality in shock patients
AU - Visser, Marlieke
AU - Vermeulen, Mechteld A. R.
AU - Richir, Milan C.
AU - Teerlink, Tom
AU - Houdijk, Alexander P. J.
AU - Kostense, Piet J.
AU - Wisselink, Willem
AU - de Mol, Bas A. J. M.
AU - van Leeuwen, Paul A. M.
AU - Oudemans-van Straaten, Heleen M.
PY - 2012
Y1 - 2012
N2 - 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 77 27), we prospectively measured plasma arginine and ADMA at intensive care unit admission, Acute Physiology and Chronic Health Evaluation (APACHE) II-(predictecl mortality) and Sequential Organ Failure Assessment (SOFA) score, and circulatory markers to investigate their relationship. Arginine concentration was decreased (34.6 (SD 17.9) mu mol/l) while ADMA concentration was within the normal range (0.46 (SD 0.18) mu mol/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
AB - 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 77 27), we prospectively measured plasma arginine and ADMA at intensive care unit admission, Acute Physiology and Chronic Health Evaluation (APACHE) II-(predictecl mortality) and Sequential Organ Failure Assessment (SOFA) score, and circulatory markers to investigate their relationship. Arginine concentration was decreased (34.6 (SD 17.9) mu mol/l) while ADMA concentration was within the normal range (0.46 (SD 0.18) mu mol/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
U2 - https://doi.org/10.1017/S0007114511004648
DO - https://doi.org/10.1017/S0007114511004648
M3 - Article
C2 - 22129964
SN - 0007-1145
VL - 107
SP - 1458
EP - 1465
JO - British journal of nutrition
JF - British journal of nutrition
IS - 10
ER -