title: Elevated Levels of Asymmetric Dimethylarginine (ADMA) in the Pericardial Fluid of Cardiac Patients Correlate with Cardiac Hypertrophy.
abstract: BACKGROUND
  Pericardial fluid (PF) contains several biologically active substances, which may provide information regarding the cardiac conditions. Nitric oxide (NO) has been implicated in cardiac remodeling. We hypothesized that L-arginine (L-Arg) precursor of NO-synthase (NOS) and asymmetric dimethylarginine (ADMA), an inhibitor of NOS, are present in PF of cardiac patients and their altered levels may contribute to altered cardiac morphology.
  
  
  METHODS
  L-Arg and ADMA concentrations in plasma and PF, and echocardiographic parameters of patients undergoing coronary artery bypass graft (CABG, n = 28) or valve replacement (VR, n = 25) were determined.
  
  
  RESULTS
  We have found LV hypertrophy in 35.7% of CABG, and 80% of VR patients. In all groups, plasma and PF L-Arg levels were higher than that of ADMA. Plasma L-Arg level was higher in CABG than VR (75.7 ± 4.6 μmol/L vs. 58.1 ± 4.9 μmol/L, p = 0.011), whereas PF ADMA level was higher in VR than CABG (0.9 ± 0.0 μmol/L vs. 0.7 ± 0.0 μmol/L, p = 0.009). L-Arg/ADMA ratio was lower in the VR than CABG (VRplasma: 76.1 ± 6.6 vs. CABGplasma: 125.4 ± 10.7, p = 0.004; VRPF: 81.7 ± 4.8 vs. CABGPF: 110.4 ± 7.2, p = 0.009). There was a positive correlation between plasma L-Arg and ADMA in CABG (r = 0.539, p = 0.015); and plasma and PF L-Arg in CABG (r = 0.357, p = 0.031); and plasma and PF ADMA in VR (r = 0.529, p = 0.003); and PF L-Arg and ADMA in both CABG and VR (CABG: r = 0.468, p = 0.006; VR: r = 0.371, p = 0.034). The following echocardiographic parameters were higher in VR compared to CABG: interventricular septum (14.7 ± 0.5 mm vs. 11.9 ± 0.4 mm, p = 0.000); posterior wall thickness (12.6 ± 0.3 mm vs. 11.5 ± 0.2 mm, p = 0.000); left ventricular (LV) mass (318.6 ± 23.5 g vs. 234.6 ± 12.3 g, p = 0.007); right ventricular (RV) (33.9 ± 0.9 cm2 vs. 29.7 ± 0.7 cm2, p = 0.004); right atrial (18.6 ± 1.0 cm2 vs. 15.4 ± 0.6 cm2, p = 0.020); left atrial (19.8 ± 1.0 cm2 vs. 16.9 ± 0.6 cm2, p = 0.033) areas. There was a positive correlation between plasma ADMA and RV area (r = 0.453, p = 0.011); PF ADMA and end-diastolic (r = 0.434, p = 0.015) and systolic diameter of LV (r = 0.487, p = 0.007); and negative correlation between PF ADMA and LV ejection fraction (r = -0.445, p = 0.013) in VR.
  
  
  CONCLUSIONS
  We suggest that elevated levels of ADMA in the PF of patients indicate upregulated RAS and reduced bioavailability of NO, which can contribute to the development of cardiac hypertrophy and remodeling.
authors: Department of Pathophysiology and Gerontology and Szentagothai Research Centre, University of Pecs, Medical School, Pecs, Hungary.
authors: Zoltan
authors: Z
authors: Nemeth
authors: Heart Institute, University of Pecs, Medical School, Pecs, Hungary.
authors: Attila
authors: A
authors: Cziraki
authors: Heart Institute, University of Pecs, Medical School, Pecs, Hungary.
authors: Sandor
authors: S
authors: Szabados
authors: Department of Applied Chemistry, University of Debrecen, Faculty of Science, Debrecen, Hungary.
authors: Bernadett
authors: B
authors: Biri
authors: Department of Applied Chemistry, University of Debrecen, Faculty of Science, Debrecen, Hungary.
authors: Sandor
authors: S
authors: Keki
authors: Department of Pathophysiology and Gerontology and Szentagothai Research Centre, University of Pecs, Medical School, Pecs, Hungary; Institute of Natural Sciences, University of Physical Education, Budapest, Hungary; Department of Physiology, New York Medical College, Valhalla, New York, United States of America.
authors: Akos
authors: A
authors: Koller
mesh_terms: D000328:Adult; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism*; D006332:Cardiomegaly / Q000175:diagnosis / Q000378:metabolism*; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000473:pathology; D009569:Nitric Oxide / Q000378:metabolism / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D000069236:Pericardial Fluid / Q000378:metabolism*; D020257:Ventricular Remodeling
chemical_list: D009569:Nitric Oxide; C018524:N,N-dimethylarginine; D001120:Arginine; D019001:Nitric Oxide Synthase