title: Continuous intrathecal glyceryl trinitrate prevents delayed cerebral vasospasm in the single-SAH rabbit model in vivo.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Cerebrovascular Research Group, Department of Intensive Care Medicine, University of Berne, Berne, Switzerland. ar.fathi@gmx.net
authors.forename: Ali Reza
authors.initials: AR
authors.lastname: Fathi
authors.forename: Serge
authors.initials: S
authors.lastname: Marbacher
authors.forename: Thilo
authors.initials: T
authors.lastname: Graupner
authors.forename: Felix
authors.initials: F
authors.lastname: Wehrli
authors.forename: Stephan M
authors.initials: SM
authors.lastname: Jakob
authors.forename: Gerhard
authors.initials: G
authors.lastname: Schroth
authors.forename: Javier
authors.initials: J
authors.lastname: Fandino
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D007278:Injections, Spinal / Q000379:methods; D002532:Intracranial Aneurysm / Q000150:complications; D008297:Male; D005996:Nitroglycerin / Q000494:pharmacology*; D011817:Rabbits; D013345:Subarachnoid Hemorrhage / Q000150:complications* / Q000188:drug therapy*; D016896:Treatment Outcome; D014665:Vasodilator Agents / Q000494:pharmacology*; D020301:Vasospasm, Intracranial / Q000188:drug therapy / Q000517:prevention & control*
chemical_list: D014665:Vasodilator Agents; D005996:Nitroglycerin