title: Reduction of cerebral infarction using the third circulation.
abstract: OBJECTIVE
  To ascertain whether ventriculosubarachnoid perfusion of the brain with an oxygen-carrying nutrient emulsion affects the volume of infarction in animals with permanent middle cerebral artery occlusion.
  
  
  METHODS
  Prospective, randomized, controlled trial.
  
  
  METHODS
  An animal laboratory in a university setting.
  
  
  METHODS
  Twenty-eight closed colony adult cats weighing between 3.5 and 4.5 kg.
  
  
  METHODS
  Cats were assigned randomly into one of three groups: untreated surgical controls, artificial cerebrospinal fluid (ACSF) perfused, or oxygenated fluorochemical (t-bis perfluorobutylethylene; F44E) nutrient emulsion (OFNE) perfused. The formulation used in this study was developed for clinical use and is currently being used in a phase 1 clinical trial in patients with severe ischemic stroke. Focal cerebral ischemia was induced by permanently clipping the middle cerebral artery via the retro-orbital approach. Treatment was initiated 90 mins postocclusion and continued for 18 hrs. Animals were killed 1 hr after the termination of perfusion, the brains were sectioned and stained with 2,3,5-triphenyltetrazolium chloride, and the infarct area was determined with a computer digitizer.
  
  
  RESULTS
  There was a significant difference in cerebral infarct volume in the OFNE-perfused animals compared with the other groups ( p<or=.015). Intracranial pressure was significantly reduced in the OFNE-perfused group relative to the surgical control group at 18 hrs ( P<or=.05). Overall, infarct volume correlated with intracranial pressure measured at the end of the treatment period (Spearman rank order, p<.001).
  
  
  CONCLUSIONS
  Fluorochemical emulsion delivery of oxygen and nutrients directly to the brain by means of ventriculocisternal perfusion is a viable treatment alternative for cerebral ischemia. In addition, this technique may control elevations in intracranial pressure following stroke.
authors.affiliation: Department of Neurology, Thomas Jefferson University, 1025 Walnut Street, 310 College Building, Philadelphia, PA 19107, USA.
authors.forename: Rodney D
authors.initials: RD
authors.lastname: Bell
authors.forename: Glenn D
authors.initials: GD
authors.lastname: Frazer
authors.forename: David G
authors.initials: DG
authors.lastname: Brock
authors.forename: Jamie
authors.initials: J
authors.lastname: Strause
authors.forename: Barbara L
authors.initials: BL
authors.lastname: Powers
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Pelura
authors.forename: Michael S
authors.initials: MS
authors.lastname: Kramer
authors.forename: Jewell L
authors.initials: JL
authors.lastname: Osterholm
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D002415:Cats; D002552:Cerebral Ventricles; D004655:Emulsions; D005466:Fluorocarbons / Q000008:administration & dosage*; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy* / Q000473:pathology; D007263:Infusions, Parenteral; D007427:Intracranial Pressure / Q000187:drug effects; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D010100:Oxygen / Q000008:administration & dosage*; D011897:Random Allocation; D018709:Statistics, Nonparametric; D013346:Subarachnoid Space
chemical_list: D004655:Emulsions; D005466:Fluorocarbons; D018696:Neuroprotective Agents; C057576:bis(perfluorobutyl)ethene; D010100:Oxygen