title: Controlled release of lipopolysaccharide in the subarachnoid space of rabbits induces chronic vasospasm in the absence of blood.
abstract: OBJECTIVE
  Leukocyte-endothelial cell interactions appear to play a role in the development of vasospasm after SAH. Using a purely inflammatory protein, LPS, we evaluated the effect of inflammation on the development of chronic vasospasm in the absence of blood and compared it to SAH-induced vasospasm in rabbits.
  
  
  METHODS
  Lipopolysaccharide was incorporated into EVAc polymers to produce 20% LPS/EVAc polymers (wt/wt). Rabbits (n = 23) were randomized to 4 experimental groups: (1) empty polymer (n = 6), (2) SAH (n = 5), (3) 0.7 mg/kg polymeric LPS dose (n = 6), and (4) 1.4 mg/kg polymeric LPS dose (n = 6). Blood and polymers were inserted into the cisterna magna. The rabbits were killed 3 days postoperatively, and the basilar arteries were harvested for morphometric analysis. Clinical response and lumen patencies were analyzed using ANOVA and a post hoc Newman-Keuls Multiple Comparisons test.
  
  
  RESULTS
  Significant narrowing of the basilar artery was observed by insertion of 20% LPS/EVAc polymers into the subarachnoid space at a polymeric dose of 1.4 mg/kg (actual dose, 66 microg kg(-1) d(-1)) (75.4% +/- 4.2%; P < .01) and by SAH (80.3% +/- 8.1%; P < .01) as compared with the empty polymer group. A trend toward narrowing was observed in the 0.7 mg/kg polymeric LPS dose group (actual dose, 33 microg kg(-1) d(-1)) (85.2% +/- 2.6%; P > .05). Symptoms associated with SAH were noted in 50% of the rabbits in the 0.7 mg/kg LPS group and in 100% of rabbits in the 1.4 mg/kg LPS group.
  
  
  CONCLUSIONS
  Controlled release of LPS into the subarachnoid space of rabbits produced chronic vasospasm in a dose-dependent manner. At a polymeric dose of 1.4 mg/kg, LPS-induced vasospasm was equivalent to that induced by SAH. This suggests that LPS and SAH may induce vasospasm through similar mechanisms and provides further evidence that inflammation plays a central role in the etiology of chronic vasospasm.
authors.affiliation: Department of Neurosurgery, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
authors.forename: Pablo F
authors.initials: PF
authors.lastname: Recinos
authors.forename: Gustavo
authors.initials: G
authors.lastname: Pradilla
authors.forename: Quoc-Anh
authors.initials: QA
authors.lastname: Thai
authors.forename: Marilyn
authors.initials: M
authors.lastname: Perez
authors.forename: Alia M
authors.initials: AM
authors.lastname: Hdeib
authors.forename: Rafael J
authors.initials: RJ
authors.lastname: Tamargo
mesh_terms: D000818:Animals; D001488:Basilar Artery / Q000187:drug effects / Q000503:physiopathology; D001798:Blood Proteins / Q000009:adverse effects / Q000378:metabolism; D002536:Cerebral Arteries / Q000187:drug effects / Q000503:physiopathology*; D002634:Chemotaxis, Leukocyte / Q000187:drug effects / Q000502:physiology; D002908:Chronic Disease; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000493:pharmacokinetics; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004660:Encephalitis / Q000209:etiology / Q000503:physiopathology*; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D018836:Inflammation Mediators / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics; D008070:Lipopolysaccharides / Q000008:administration & dosage* / Q000378:metabolism / Q000493:pharmacokinetics; D011145:Polyvinyls / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D011817:Rabbits; D013345:Subarachnoid Hemorrhage / Q000150:complications / Q000503:physiopathology*; D013346:Subarachnoid Space / Q000187:drug effects / Q000503:physiopathology*; D014654:Vascular Patency / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology; D020301:Vasospasm, Intracranial / Q000209:etiology / Q000503:physiopathology*
chemical_list: D001798:Blood Proteins; D003692:Delayed-Action Preparations; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D011145:Polyvinyls; C016438:ethylenevinylacetate copolymer