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ADMA Levels and Arginine/ADMA Ratios Reflect Severity of Disease and Extent of Inflammation After Subarachnoid Hemorrhage

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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.

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Acknowledgments

We would like to thank the staff at our high dependency and intensive care units. Without their dedicated work, this study could not have been performed. We also extend a special thanks to our research nurses for their invaluable help and support. The Swedish Society of Medicine, the Faculty of Medicine at Umeå University, and The Stroke Foundation of Northern Sweden supported this study.

Conflict of interest

Cecilia Lindgren, Magnus Hultin, Lars-Owe Koskinen, Peter Lindvall, Ljubisa Borota, and Silvana Naredi declare that they have no conflict of interests.

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Authors and Affiliations

  1. Department of Surgical and Perioperative Sciences, Anesthesiology and Intensive Care, Umeå University, 901 87, Umeå, Sweden

    Cecilia Lindgren, Magnus Hultin & Silvana Naredi

  2. Department of Pharmacology and Clinical Neuroscience, Neurosurgery, Umeå University, 901 87, Umeå, Sweden

    Lars-Owe D. Koskinen & Peter Lindvall

  3. Department of Radiology, Oncology and Radiation Science, Uppsala University, 751 05, Uppsala, Sweden

    Ljubisa Borota

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  1. Cecilia Lindgren
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Correspondence to Cecilia Lindgren.

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Lindgren, C., Hultin, M., Koskinen, LO.D. et al. ADMA Levels and Arginine/ADMA Ratios Reflect Severity of Disease and Extent of Inflammation After Subarachnoid Hemorrhage. Neurocrit Care 21, 91–101 (2014). https://doi.org/10.1007/s12028-013-9945-8

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