Intracarotid infusions of protamine sulfate disrupt the blood-brain barrier of rabbits.

This study examined the effect of intracarotid infusions of protamine sulfate on the blood-brain barrier of the rabbit. Evans blue, which binds tightly to serum albumin, served as the marker for blood-brain barrier disruption. Brains from 12 of 14 rabbits receiving 30-50 mg of protamine sulfate in an intracarotid infusion over 3 min demonstrated intense Evans blue-albumin staining in the distribution of the infused internal carotid artery. In contrast, brains from 5 animals receiving 0.9% saline and from 5 animals receiving 50 mg of protamine sulfate by the intravenous route showed no evidence of blood-brain barrier disruption. Premixing protamine sulfate with heparin prior to intracarotid administration greatly reduced or abolished Evans blue staining of the brain as did delayed administration of the marker dye. Thus, the interaction of the positively charged protamine molecule with the vascular endothelium of cerebral capillaries transiently alters the permeability of the blood-brain barrier in the rabbit.