Subarachnoid haemorrhage induces an inflammatory response followed by a delayed persisting increase in asymmetric dimethylarginine

Abstract

Objective. Subarachnoid haemorrhage (SAH) is associated with an inflammatory systemic response and cardiovascular complications. Asymmetric dimethyl arginine (ADMA), an endogenous inhibitor of nitric oxide synthase, mediates vasoconstriction and might contribute to cerebral vasoconstriction and cardiovascular complications after SAH. ADMA is also involved in inflammation and induces endothelial dysfunction. The aim of this study was to evaluate whether and how CRP (marker for systemic inflammation) and ADMA increased in patients during the acute phase (first week) after SAH. The ADMA level was also assessed in the patients in a non-acute phase (three months), and in healthy controls. Methods. A prospective study of 20 patients with aneurysmal SAH. ADMA and CRP were followed daily during the first week after SAH and a follow up sample for ADMA was obtained 3 months later. A single blood sample for ADMA was collected from age- and sex-matched healthy controls (n = 40, two for each case). Results. CRP increased significantly from day 2; 16 (Confidence interval (CI) 10–23) mg/L to day 4; 84 (CI 47–120) mg/L, (p < 0.01). ADMA increased significantly from day 2; 0.22 (CI 0.17–0.27) μmol/L, to day 7; 0.37 (CI 0.21–0.54) μmol/L, p < 0.01. ADMA remained elevated at a 3-month follow-up: 0.36 (CI 0.31–0.42) μmol/L. ADMA in the first sample from the patients (day 1–3); 0.25 (CI 0.19–0.30) μmol/L, was not different from ADMA in matched healthy controls; 0.25 (CI 0.20–0.31), p > 0.05. Conclusion. After SAH, CRP and ADMA in serum increased significantly during the first week and ADMA remained elevated 3 months later.

Key Words::

• Acute-phase reaction
• C-reactive protein
• subarachnoid hemorrhage
• intracranial aneurysm
• arginine/administration & dosage/analogs & derivatives/blood

Acknowledgements

We express our gratitude to the research nurses at the neurosurgical department for their invaluable enthusiasm and quality of work.

This study was supported by grants from the Swedish Medical Society SLS-97381, the Neurological Foundation at Umeå University and the Faculty of Medicine at Umeå University, Sweden.

Parts of the results were presented as an abstract at ESCIM 2006, September 24–27, Barcelona, Spain.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.