Abstract 190: Repeated Doses of Dodecafluoropentane Emulsion Provide Neuroprotection Up to 24 Hours Following Cerebral Artery Occlusion in Rabbits

Abstract

Introduction: Neuroprotective strategies in ischemic stroke include oxygen delivery to sustain penumbra and prevent hypoxic cell death. Hyperbaric oxygen, blood substitutes, and liquid fluorocarbon-based oxygen carriers have often failed in treatment of stroke and other ischemic disorders. Dodecafluoropentane emulsion (DDFPe, boiling point 29°C) shifts to quasi-gas phase at body temperature, which allows absorption and transportation of very high levels of oxygen. Exceptionally small particle size, 250-300 nm, may allow oxygen delivery even through occluded vessels, by diffusion into hypoxic tissue unreachable by whole blood. In a preliminary stroke study in rabbits, DDFPe reduced infarct volumes in all experimental groups by 80% or more. Hypothesis: Repeated doses of DDFPe can reduce infarct volume for up to 24 hours after permanent cerebral artery occlusion in rabbits. Methods: New Zealand White rabbits (N=55) received cerebral angiography from a femoral artery approach. Embolic microspheres (diameter=700-900 μm) were injected into the internal carotid artery, permanently occluding the middle cerebral and/or anterior cerebral arteries. Rabbits were randomly assigned to treatment groups and sacrifice times as in Table 1. In all treated groups, intravenous DDFPe dosing with a 2% w/v emulsion began at 1 hour post-embolization and was repeated every 90 minutes until sacrifice at either 7 or 24 hours post-embolization. Following sacrifice, infarcts were measured as a percent of brain volume using vital stains on brain sections. Results: Percent infarct volume means significantly decreased for all DDFPe treated groups compared with controls (Table 1). Conclusion: Intravenous DDFPe begun 1 hour after stroke onset protects the brain from ischemic injury in the rabbit model of permanent embolic stroke. Decreased infarct volumes represent salvaged brain tissue. This effect can be observed for 24 hours with repeated doses.