title: ADMA levels and arginine/ADMA ratios reflect severity of disease and extent of inflammation after subarachnoid hemorrhage.
abstract: BACKGROUND
  Subarachnoid hemorrhage (SAH) is characterized by an inflammatory response that might induce endothelial dysfunction. The aim of this study was to evaluate if ADMA and arginine/ADMA ratios after SAH (indicators of endothelial dysfunction) are related to clinical parameters, inflammatory response, and outcome.
  
  
  METHODS
  Prospective observational study. ADMA, arginine, C-reactive protein (CRP), and cytokines were obtained 0-240 h (h) after SAH. Definition of severe clinical condition was Hunt&Hess (H&H) 3-5 and less severe clinical condition H&H 1-2. Impaired cerebral circulation was assessed by clinical examination, transcranial doppler, CT-scan, and angiography. Glasgow outcome scale (GOS) evaluated the outcome.
  
  
  RESULTS
  Compared to admission, 0-48 h after SAH, the following was observed 49-240 h after SAH; (a) ADMA was significantly increased at 97-240 h (highest 217-240 h), (b) CRP was significantly increased at 49-240 h (highest 73-96 h), (c) interleukin-6 (IL-6) was significantly lower at 97-240 h (highest 49-96 h), p < 0.05. ADMA, CRP, and IL-6 were significantly lower and peak arginine/ADMA ratio was significantly higher in patients with H&H 1-2 compared to patients with H&H 3-5, p < 0.05. The peak ADMA or the nadir arginine/ADMA ratio did not differ significantly between patients with (55%) or without (45%) signs of impaired cerebral circulation. The peak ADMA or the nadir arginine/ADMA ratio did not differ significantly between patients with GOS 1-3 and patients with GOS 4-5.
  
  
  CONCLUSIONS
  ADMA increased significantly after SAH, and the increase in ADMA started after the pro-inflammatory markers (CRP and IL-6) had peaked. This might indicate that endothelial dysfunction, with ADMA as a marker, is induced by a systemic inflammation.
authors.affiliation: Department of Surgical and Perioperative Sciences, Anesthesiology and Intensive Care, Umeå University, 901 87, Umeå, Sweden, Cecilia.lindgren@anestesi.umu.se.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Lindgren
authors.forename: Magnus
authors.initials: M
authors.lastname: Hultin
authors.forename: Lars-Owe D
authors.initials: LO
authors.lastname: Koskinen
authors.forename: Peter
authors.initials: P
authors.lastname: Lindvall
authors.forename: Ljubisa
authors.initials: L
authors.lastname: Borota
authors.forename: Silvana
authors.initials: S
authors.lastname: Naredi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000032:analysis; D016207:Cytokines / Q000097:blood; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood*; D008297:Male; D008875:Middle Aged; D012720:Severity of Illness Index; D013345:Subarachnoid Hemorrhage / Q000097:blood* / Q000503:physiopathology*
chemical_list: D015415:Biomarkers; D016207:Cytokines; C018524:N,N-dimethylarginine; D002097:C-Reactive Protein; D001120:Arginine