TECHNIQUE OF, AND COMPLICATIONS ATTRIBUTABLE TO, REPEATED HYPEROSMOTIC BLOOD-BRAIN-BARRIER DISRUPTION IN DOGS

Objective-To design a repeatable technique for reversible, hyperosmoti c blood-brain barrier disruption (BBBD) in dogs and evaluate clinical effects of multiple BBBD. Animals-10 healthy adult dogs. Procedure-Usi ng fluoroscopic guidance, an arterial catheter was directed into the i nternal carotid artery via the femoral artery of 10 dogs. Blood-brain barrier disruption was achieved in 5 dogs, using intracarotid infusion of mannitol. Five control dogs received only saline solution. After r ecovery, dogs were monitored for clinical signs of disease before a se cond, nonsurvival procedure was performed 2 to 3 weeks later. BBBD was estimated, using computed tomographic (CT) densitometry values, as we ll as Evan's blue dye staining on necropsy specimens. Results-Seven do gs completed the entire study. Two treatment dogs were lost after the first infusion because of deteriorating neurologic function attributed to CNS edema and increased intracranial pressure. One control dog was lost because of vessel wall damage during catheterization. The remain ing dogs had only transient neurologic, ocular, and vasculature injuri es. Successful BBBD was documented in all treated dogs by use of CT an d Evan's blue dye evaluation. Conclusion-Repeated catheterization of t he internal carotid artery and disruption of the blood-brain barrier i s possible in dogs. Clinical Relevance-Refinement of this technique wo uld be useful not only for improved delivery of chemotherapeutic agent s in patients with brain tumors, but also would allow further investig ation of new treatments involving genetically engineered retroviruses and monoclonal antibodies.