Abstract 9303: Dodecafluoropentane Emulsion Decreases Cerebral Infarcts in a Rabbit Embolic Stroke Model
Introduction Dodecafluoropentane emulsion (DDFPe) absorbs, transports, and delivers very high levels of oxygen in vitro and in vivo, with the potential to protect tissues during varied ischemic episodes including stroke. DDFPe may be beneficial by protecting cells during hypoxic perturbations such as myocardial infarction, cardiac surgery, carotid interventions, or stroke. For clinical success in current stroke therapy, tPA must be given within 4.5-hours of onset. Agents that can extend this time frame by delaying ischemic damage have the potential to increase access to thrombolysis treatment and improve outcomes. Using a rabbit model of acute insoluble embolic stroke, we describe the efficacy of DDFPe at decreasing infarct volumes.
Hypothesis We assessed the hypothesis that treatment with DDFPe effectively decreases infarct volumes without lysis of the arterial occlusion.
Methods New Zealand White rabbits (N=45, 5.1±0.50 kg) received angiography and three embolic spheres (700-900 µm diameter) were injected into the internal carotid artery, permanently occluding the middle cerebral artery. Rabbits were randomly assigned to control (N=7, embolized without treatment) or one of three DDFPe treatment start times: pre-treatment 30-min before stroke (N=7), hyperacute treatment 0-30 min after stroke (N=13) or acute treatment 1-3 hours after stroke (N=18). DDFPe dose was 2% w/v intravenous injection, 0.6 ml/kg, at the group start time and repeated every 90 minutes as time allowed. Following euthanasia at 4 hours infarct volume was measured using vital stains on brain sections.
Results Percent infarct volumes were decreased (P=0.001) for all DDFPe treated rabbits (0.73±0.51%, N=38) compared with controls (3.57±0.67%). DDFPe pre-treatment (0.64±0.65%), hyperacute treatment (0.73±0.48%) and acute treatment (0.76±0.40%) all significantly decreased infarct volumes compared to controls (P=0.021, 0.021, and 0.005, respectively).
Conclusions DDFPe protects ischemic brain from hypoxia and decreases infarct volumes. Further testing is warranted of DDFPe as a therapeutic agent where delivery of oxygen may be of great benefit. Potential clinical applications may be much broader and development is urgently needed.
- © 2011 by American Heart Association, Inc.