Acta Neurochirurgica

, Volume 153, Issue 8, pp 1669–1675 | Cite as

Continuous intrathecal glyceryl trinitrate prevents delayed cerebral vasospasm in the single-SAH rabbit model in vivo

  • Ali Reza FathiEmail author
  • Serge Marbacher
  • Thilo Graupner
  • Felix Wehrli
  • Stephan M. Jakob
  • Gerhard Schroth
  • Javier Fandino
Experimental research



Delayed cerebral vasospasm after aneurysmal subarachnoid hemorrhage (SAH) is a major cause of high morbidity and mortality. The reduced availability of nitric oxide (NO) in blood and cerebrospinal fluid (CSF) is well established as a key mechanism of vasospasm. Systemic administration of glyceryl trinitrate (GTN), an NO donor also known as nitroglycerin, has failed to be established in clinical settings to prevent vasospasm because of its adverse effects, particularly hypotension. The purpose of this study was to analyze the effect of intrathecally administered GTN on vasospasm after experimental SAH in the rabbit basilar artery.


A single-hemorrhage model of SAH in rabbits was used to induce vasospasm. GTN (0.5 mg/ml) or saline was infused via a subcutaneous implanted osmotic pump with continuous drug release into the cerebellomedullary cistern over 5 days. The degree of vasospasm in the basilar artery was recorded with angiography on day 5 after SAH and was compared to baseline angiography on day 0.


Significant reduction of basilar artery diameter was observed in the SAH group with saline infusion compared to sham-operated animals. Intrathecally administered GTN had no effect on the vessel diameter in sham-operated animals, whereas it significantly prevented vasospasm in the SAH group. Intrathecal GTN infusion did not affect arterial blood pressure.


Prophylactic, continuous intrathecal administration of GTN prevents vasospasm of the basilar artery in the rabbit SAH model. No toxic effects could be demonstrated in this study. The clinical safety and feasibility of this strategy need to be further investigated.


Subarachnoid hemorrhage Cerebral vasospasm Delayed ischemic neurological deficits Nitroglycerin Nitric oxide donors 


Conflicts of interest



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Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Ali Reza Fathi
    • 1
    • 2
    Email author
  • Serge Marbacher
    • 1
    • 2
  • Thilo Graupner
    • 1
    • 4
  • Felix Wehrli
    • 1
    • 4
  • Stephan M. Jakob
    • 1
  • Gerhard Schroth
    • 3
  • Javier Fandino
    • 1
    • 2
  1. 1.Cerebrovascular Research Group, Department of Intensive Care MedicineUniversity of BerneBerneSwitzerland
  2. 2.Department of NeurosurgeryKantonsspital AarauAarauSwitzerland
  3. 3.Institute of Diagnostic and Interventional NeuroradiologyUniversity Hospital Inselspital BernBernSwitzerland
  4. 4.Department of NeurosurgeryUniversity Hospital Inselspital BernBernSwitzerland

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