Progress in dodecafluoropentane emulsion as a neuroprotective agent in a rabbit stroke model.

Abstract

Dodecafluoropentane emulsion (DDFPe) in 250 nm nanodroplets seems to swell modestly to accept and carry large amounts of oxygen in the body at >29 °C. Small particle size allows oxygen delivery even into hypoxic tissue unreachable by erythrocytes. Using permanent cerebral embolic occlusion in rabbits, we assessed DDFPe dose response as a neuroprotectant at 7 and 24 h post-embolization without lysis of arterial obstructions and investigated blood pharmacokinetics. New Zealand White rabbits (N = 56) received cerebral angiography and embolic spheres (diameter = 700-900 μm) occluded middle and/or anterior cerebral arteries. Intravenous DDFPe dosing (2 % w/v emulsion) began at 60 min and repeated every 90 min until sacrifice at 7 or 24 h post-embolization. Seven-hour groups: (1) control (embolized without treatment, N = 6), and DDFPe treatment: (2) 0.1 ml/kg (N = 7), (3) 0.3 ml/kg (N = 9), (4) 0.6 ml/kg (N = 8). Twenty-four-hour groups: (5) control (N = 16), and DDFPe treatment: (6) 0.1 ml/kg (N = 10). Infarcts as percent of total brain volume were determined using vital stains on brain sections. Other alert normal rabbits (N = 8) received IV doses followed by rapid arterial blood sampling and GC-MS analysis. Percent infarct volume means significantly decreased for all DDFPe-treated groups compared with controls, p = <0.004 to <0.03. Blood DDFP (gas) half-life was 1.45 ± 0.17 min with R = 0.958. Mean blood clearance was 78.5 ± 24.9 ml/min/kg (mean ± SE). Intravenous DDFPe decreases ischemic stroke infarct volumes. Blood half-life values are very short. The much longer therapeutic effect, >90 min, suggests multiple compartments. Lowest effective dose and maximum effective therapy duration are not yet defined. Rapid development is warranted.

• Authors: S D Woods, R D Skinner, A M Ricca, A T Brown, J D Lowery, M J Borrelli, J O Lay, W C Culp
• Journal: Molecular neurobiology (Mol Neurobiol) Vol. 48 Issue 2 Pg. 363-7 (Oct 2013) ISSN: 1559-1182 [Electronic] United States
• PMID: 23813100 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Emulsions
• Fluorocarbons
• Neuroprotective Agents
• perfluoropentane

Topics

• Animals
• Brain (drug effects, pathology)
• Cerebral Infarction (drug therapy, pathology)
• Disease Models, Animal
• Emulsions
• Fluorocarbons (blood, pharmacology, therapeutic use)
• Neuroprotective Agents (pharmacology, therapeutic use)
• Rabbits
• Stroke (drug therapy, pathology)
• Time Factors