title: Dose-response relationship of locally applied nimodipine in an ex vivo model of cerebral vasospasm.
abstract: BACKGROUND
  Cerebral vasospasm is a severe complication of subarachnoid hemorrhage (SAH). The calcium channel inhibitor nimodipine has been used for treatment of cerebral vasospasm. No evidence-based recommendations for local nimodipine administration at the site of vasospasm exist. The purpose of this study was to quantify nimodipine's local vasodilatory effect in an ex vivo model of SAH-induced vasospasm.
  
  
  METHODS
  SAH-induced vasospasm was modeled by contracting isolated segments of rat superior cerebellar arteries with a combination of serotonin and a synthetic analog of prostaglandin A(2). A pressure myograph system was used to determine vessel reactivity of spastic as well as non-spastic arteries.
  
  
  RESULTS
  Compared to the initial vessel diameter, a combination of serotonin and prostaglandin induced considerable vasospasm (55 ± 2.5 % contraction; n = 12; p < 0.001). Locally applied nimodipine dilated the arteries in a concentration-dependent manner starting at concentrations as low as 1 nM (n = 12; p < 0.05). Concentrations higher than 100 nM did not relevantly increase the vasodilatory effect. Nimodipine's vasodilatory effect was smaller in spastic than in non-spastic vessels (n = 12; p < 0.05), which we assume to be due to structural changes in the vessel wall.
  
  
  CONCLUSIONS
  The described ex vivo model allows to investigate the dose-dependent efficacy of spasmolytic drugs prior to in vivo experiments. Low concentrations of locally applied nimodipine have a strong vasodilatory effect, which is of relevance when considering the local application of nimodipine in cerebral vasospasm.
authors.affiliation: Experimental Radiation Oncology, University Medical Center Mannheim, Mannheim, Germany.
authors.forename: Fatih
authors.initials: F
authors.lastname: Seker
authors.forename: Jürgen
authors.initials: J
authors.lastname: Hesser
authors.forename: Eva
authors.initials: E
authors.lastname: Neumaier-Probst
authors.forename: Christoph
authors.initials: C
authors.lastname: Groden
authors.forename: Marc A
authors.initials: MA
authors.lastname: Brockmann
authors.forename: Rudolf
authors.initials: R
authors.lastname: Schubert
authors.forename: Carolin
authors.initials: C
authors.lastname: Brockmann
mesh_terms: D000818:Animals; D002536:Cerebral Arteries / Q000187:drug effects* / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D008297:Male; D009553:Nimodipine / Q000008:administration & dosage*; D051381:Rats; D017208:Rats, Wistar; D016896:Treatment Outcome; D014655:Vascular Resistance / Q000187:drug effects; D014665:Vasodilator Agents / Q000008:administration & dosage; D020301:Vasospasm, Intracranial / Q000188:drug therapy* / Q000503:physiopathology*
chemical_list: D014665:Vasodilator Agents; D009553:Nimodipine