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

Abstract

This is an accepted version of a paper published in Scandinavian Journal of Clinical and Laboratory Investigation. This paper has been peer-reviewed but does not include the final publisher proof-corrections or journal pagination.Citation for the published paper: Rodling Wahlström, M., Olivecrona, M., Koskinen, L., Naredi, S., Hultin, M. (2012) "Subarachnoid haemorrhage induces an inflammatory response followed by a delayed persisting increase in asymmetric dimethylarginine" Scandinavian Journal of Clinical and Laboratory Investigation, Access to the published version may require subscription. AbstractObject: 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: 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 three months later. A single blood sample for ADMA was collected from age and sex matched healthy controls (n=40, 2 for each case). Conclusion:After SAH, CRP and ADMA in serum increased significantly during the first week and ADMA remained elevated three months later.

Low Plasma Arginine:Asymmetric Dimethyl Arginine Ratios Predict Mortality After Intracranial Aneurysm Rupture

“…19 ADMA levels were within the 0.2 to 0.4μmol/L range, which is similar to our findings, though we did not see such a marked increase. 19 Peripheral endothelial dysfunction and reduced plasma L-arginine:ADMA ratio have been shown to occur in the first 5 days after ischemic stroke, which is different from our observation: that whereas changes in ADMA and arginine do occur after SAH, the arginine:ADMA ratio remains overall stable.…”

“…[14][15][16][17][18] In a recent study, plasma ADMA was found to increase over the first week after SAH. 19 In addition, high concentrations of ADMA in cerebrospinal fluid have been found to associate with cerebral vasospasm in humans and in primates with experimentally induced SAH. 11,20,21 The aim of this prospective observational study was to investigate if circulating ADMA, arginine, arginine:ADMA ratio, and NOx are associated with survival after SAH.…”

“…46 Our finding that neither ADMA, arginine, or arginine:ADMA was related to V MCA is in line with previous findings, though they are limited in numbers. 19,21,47 Biological explanations may be that first, systemic ADMA is not a reflection of intracellular concentrations; second, the plasma ADMA is too low in concentration to limit arginine transport; 48 and third, the effect of ADMA may be on the microvascular level in reducing blood flow. In contrast to this, we found that higher serum NOx concentration associated with lower V MCA ( Figure 3A).…”

Risk Factors for Hemorrhagic Complications following Pipeline Embolization Device Treatment of Intracranial Aneurysms: Results from the International Retrospective Study of the Pipeline Embolization Device

“…While most of the ruptured aneurysms treated in this study were not treated in the acute phase of subarachnoid hemorrhage, studies suggest that acute-phase proteins can remain elevated for several months following subarachnoid hemorrhage. 24 Another hypothesis that has been suggested regarding the etiology of IPH is one of hyperperfusion following PED placement. This is thought to be due to a sudden loss of a large capacitance chamber in the form of a giant aneurysm.…”

The role of inflammation and potential use of sex steroids in intracranial aneurysms and subarachnoid hemorrhage

“…[ 25 ] Asymmetric dimethyl arginine (ADMA), an endogenous inhibitor of nitric oxide synthase and a marker of endothelial dysfunction and inflammation, was also shown be increased starting from day 2 and was highest approximately 9–10 days after SAH. [ 76 114 ] Higher levels of macrophage migration inhibitory factor (MIF), soluble CD40 ligand (sCD40L), and platelet-derived growth factor (PDGF)-BB were also correlated with poor outcome. [ 23 70 ] aSAH patients may also experience cardiopulmonary complications as part of the systemic reaction.…”