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Journal of Neuroinflammation 2017-Dec

Dimethylarginines in patients with intracerebral hemorrhage: association with outcome, hematoma enlargement, and edema.

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Hans Worthmann
Na Li
Jens Martens-Lobenhoffer
Meike Dirks
Ramona Schuppner
Ralf Lichtinghagen
Jan T Kielstein
Peter Raab
Heinrich Lanfermann
Stefanie M Bode-Böger

Nyckelord

Abstrakt

BACKGROUND

Asymmetric dimethylarginine (ADMA)--the most potent endogenous NO-synthase inhibitor, has been regarded as mediator of endothelial dysfunction and oxidative stress. Considering experimental data, levels of ADMA and its structural isomer symmetric dimethylarginine (SDMA) might be elevated after intracerebral hemorrhage (ICH) and associated with clinical outcome and secondary brain injury.

METHODS

Blood samples from 20 patients with acute ICH were taken at ≤ 24 h and 3 and 7 days after the event. Nine patients had favorable (modified Rankin Scale (mRS) at 90 days 0-2) outcome, and 11 patients unfavorable outcome (mRS 3-6). Patients' serum ADMA, SDMA, and L-arginine levels were determined by high-performance liquid chromatography-tandem mass spectrometry. Levels were compared to those of 30 control subjects without ICH. For further analysis, patients were grouped according to outcome, hematoma and perihematomal edema volumes, occurrence of hematoma enlargement, and cytotoxic edema as measured by computed tomography and serial magnetic resonance imaging.

RESULTS

Levels of ADMA--but not SDMA and L-arginine--were elevated in ICH patients compared to controls (binary logistic regression analysis: ADMA ≤ 24 h, p = 0.003; 3 days p = 0.005; 7 days p = 0.004). If patients were grouped according to outcome, dimethylarginines were increased in patients with unfavorable outcome. The binary logistic regression analysis confirmed an association of SDMA levels ≤ 24 h (p = 0.048) and at 3 days (p = 0.028) with unfavorable outcome. ADMA ≤ 24 h was increased in patients with hematoma enlargement (p = 0.003), while SDMA ≤ 24 h was increased in patients with large hematoma (p = 0.029) and perihematomal edema volume (p = 0.023).

CONCLUSIONS

Our data demonstrate an association between dimethylarginines and outcome of ICH. However, further studies are needed to confirm this relationship and elucidate the mechanisms behind.

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