Abstract 17458: Dodecafluoropentane Emulsion Decreases Stroke Volume in a Rat Permanent Occlusion Stroke Model
Introduction: Dodecafluoropentane emulsion (DDFPe) offers a safe, simple, and effective means of reducing infarct volume by transporting oxygen to areas inaccessible to red blood cells, thus prolonging the window for stroke intervention. Whereas other experimental oxygen delivery systems have failed in clinical trials due to either toxicity or impracticality, DDFPe is biologically inert, quickly clears from the body, and has been shown upon repeated doses to reduce infarct volume up to 24 hours post-ischemia in a rabbit permanent occlusion model. The success of the current study in rats provides a second animal model, required by the FDA for progression to human trials, as well as an excellent model for future mechanistic investigation of DDFPe.
Hypothesis: Repeated doses of DDFPe will reduce infarct volumes in rats following permanent occlusion of the middle cerebral artery (MCA).
Methods: Spontaneously hypertensive rats (N=21) underwent cauterization of the MCA, permanently occluding the vessel. Rats were randomly assigned to control and treatment groups and sacrificed 6 hours following vascular occlusion. Treatment rats intravenously received 2% w/v doses of DDFPe, standardized at 0.6 mL/kg, 1 hour after MCA cauterization followed by repeat doses every 90 minutes until sacrifice. Following euthanasia, the brains were harvested, sectioned, and treated with TTC (2,3,5-triphenyltetrazolium chloride) vital staining. Infarct volume was subsequently quantified using ImageJ, an imaging evaluation software.
Results: Percent infarct volumes were significantly decreased (P=0.0007) for the DDFPe treated rats (1.7±0.5%, N=11) as compared to the controls (8.4±1.9%, N=10).
Conclusion: Repeated doses of DDFPe protect the ischemic brain from hypoxic insult and decrease infarct volume following permanent occlusion in a rat model. This model will facilitate further mechanistic and pharmacokinetic study necessary for the imminent clinical evaluation of DDFPe.
- © 2013 by American Heart Association, Inc.