THE EFFECTS OF PENTOBARBITAL ON BLOOD-BRAIN-BARRIER DISRUPTION CAUSEDBY INTRACAROTID INJECTION OF HYPEROSMOLAR MANNITOL IN RATS

This study was performed to evaluate both the effects of pentobarbital on disruption of the blood-brain barrier (BBB) by hyperosmolar mannit ol and the relationship between its effect on blood pressure and the i ntegrity of the BBB. Under isoflurane anesthesia, rats in the control group were infused with 25% mannitol into the internal carotid artery before measuring the transfer coefficient (K-i) of C-14 alpha-aminoiso butyric acid. Ten minutes before the administration of mannitol, rats received an infusion of pentobarbital: 20 mg/kg in the small-dose grou p and 50 mg/kg in the large-dose group. In another group of animals (h ydralazine group), hydralazine was administered to maintain the mean a rterial blood pressure (MAP) at 65 mm Hg during the experimental perio d. The MAP of the control group (113 +/- 14 mm Hg) was significantly h igher (P < 0.002) than that of the small-dose pentobarbital group (78 +/- 13 mm Hg) or the large-dose pentobarbital group (68 +/- 14 mm Hg). In the control group, the K-i of the cortex ipsilateral to the mannit ol injection was increased to 4.5 times that of the contralateral cort ex (14.5 +/- 7.7 vs 3.2 +/- 0.6 mu L . g(-1) . min(-1); P < 0.002). Th e K-i of the ipsilateral cortex of the small-dose pentobarbital group was 9.7 +/- 5.6 mu L . g(-1) . min(-1). The K-i of the ipsilateral cor tex of the large-dose pentobarbital group was 5.5 +/- 2.9 mu L . g(-1) . min(-1),and lower (-9.0 mu L . g(-1) . min(-1)) than that of the co ntrol animals (P < 0.05). There was no significant difference in the K i of the contralateral cortex among any of the three groups of animals . At the same MAP, the K-i of the ipsilateral cortex of the large-dose pentobarbital group was lower (-4.3 mu L . g(-1) . min(-1)) than that of the hydralazine group (9.8 +/- 4.6 mu L . g(-1) . min(-1)) (P < 0. 05). Pentobarbital attenuated the BBB disruption induced by hyperosmol ar mannitol. This may be attributed, at least in part, to the blood pr essure effect of pentobarbital. Implications: When the blood-brain bar rier (BBB) was disrupted by a hyperosmolar solution, pentobarbital att enuated the degree of leakage of the BBB. Systemic hypotension caused by pentobarbital played a significant role in decreasing the leakage. Our study suggests that when the BBB is disrupted, pentobarbital may b e effective in protecting the BBB. Furthermore, systemic blood pressur e plays an important role in determining the degree of disruption.