L-arginine and Asymmetric Dimethylarginine (ADMA) levels in pericardial fluid in patients undergoing open heart surgery

Abstract

Purpose: The primary function of pericardial fluid (PF) to ensure a proper friction between the pericardium and the heart. However, recent findings suggest that PF contains several biological active substances, which may reflect the function of the heart. Such molecules are L-arginine and its methylated derivative asymmetric dimethylarginine (ADMA), which may affect the function of endothelial nitric oxide synthase (eNOS), thus production and/or bioavailability of NO. We hypothesized that L-arginine and ADMA are present in PF, and their concentrations are different in CABG and VR groups, and correlates with morphological parameters of the heart. Methods: Plasma and PF were collected from patients undergoing open coronary artery bypass graft (CABG, n=28) and valve replacement (VR, n=15) and concentrations of L-arginine and ADMA were determined using liquid chromatography mass spectrometry (LC-MS). Cardiac wall parameters were determined by echocardiography. Results: We found the following significant (p<0.05) differences: In both groups, the level of both plasma and PF L-arginine was higher than that of ADMA (CABG, plasma L-arginine vs. plasma ADMA: 75.7mmol/L vs. 0.7mmol/L, PF L-arginine vs. PF ADMA: 76.9mmol/L vs. 0.7mmol/L; VR, plasma L-arginine vs. plasma ADMA: 57.7mmol/L vs. 0.8mmol/L, PF L-arginine vs. PF ADMA: 71.5mmol/L vs. 0.9mmol/L). Furthermore, the level of plasma L-arginine was higher in the CABG group compared to the VR group, and the level of PF ADMA was higher in the VR group compared to the CABG group. Both the plasma and PF L-arginine/ADMA ratios were higher in the CABG group compared to the VR group (plasma: 125.4 vs. 74.9; PF: 110.4 vs. 79.5). The thickness of interventricular septum (IVS) and the posterior wall (PW), as well as the right ventricular (RV) and right atrial (RA) areas were higher in the VR group compared to the CABG group. In addition, the left ventricular mass (LVM) was higher in the VR group compared to the CABG group. In the VR group, we found a positive correlation between the level of PF ADMA and the left ventricular end-systolic diameter (Ds). Also, in the VR group, there was a positive correlation between the level of plasma ADMA and the RV. Furthermore, in the VR group, we found a negative correlation between the PF L-arginin/ADMA ratio and the Ds. Conclusions: On the basis of these findings we propose that the positive correlation between the concentration of PF ADMA and the cardiac parameters indicates reduced production and/or availability of endothelial NO, which may influence both the coronary circulation and the morphology of cardiac wall.