Reduction of cerebral infarction using the third circulation

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. Design: Prospective, randomized, controlled trial. Setting: An animal laboratory in a university setting. Subjects: Twenty-eight closed colony adult cats weighing between 3.5 and 4.5 kg. Interventions: 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. Measurements and Main Results: There was a significant difference in cerebral infarct volume in the OFNE-perfused animals compared with the other groups (p less than or equal to.015). Intracranial pressure was significantly reduced in the OFNE-perfused group relative to the surgical control group at 18 hrs (p less than or equal to5.05). 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.