Technique of, and complications attributable to, repeated hyperosmotic blood-brain barrier disruption in dogs.

OBJECTIVE

To design a repeatable technique for reversible, hyperosmotic blood-brain barrier disruption (BBBD) in dogs and evaluate clinical effects of multiple BBBD.

ANIMALS

10 healthy adult dogs.

PROCEDURE

Using fluoroscopic guidance, an arterial catheter was directed into the internal 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 recovery, dogs were monitored for clinical signs of disease before a second, nonsurvival procedure was performed 2 to 3 weeks later. BBBD was estimated, using computed tomographic (CT) densitometry values, as well as Evan's blue dye staining on necropsy specimens.

RESULTS

Seven dogs 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 remaining dogs had only transient neurologic, ocular, and vasculature injuries. Successful BBBD was documented in all treated dogs by use of CT and Evan's blue dye evaluation.

CONCLUSION

Repeated catheterization of the internal carotid artery and disruption of the blood- brain barrier is possible in dogs.

CLINICAL RELEVANCE

Refinement of this technique would be useful not only for improved delivery of chemotherapeutic agents in patients with brain tumors, but also would allow further investigation of new treatments involving genetically engineered retroviruses and monoclonal antibodies.