Reduction of cerebral infarction using the third circulation.

Abstract

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. Prospective, randomized, controlled trial. An animal laboratory in a university setting. Twenty-eight closed colony adult cats weighing between 3.5 and 4.5 kg. 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. 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). 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.