The effects of pentobarbital on blood-brain barrier disruption caused by 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 mannitol and the relationship between its effect on blood pressure and the integrity 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 (Ki) of 14C alpha-aminoisobutyric acid. Ten minutes before the administration of mannitol, rats received an infusion of pentobarbital: 20 mg/kg in the small-dose group and 50 mg/kg in the large-dose group. In another group of animals (hydralazine group), hydralazine was administered to maintain the mean arterial blood pressure (MAP) at 65 mm Hg during the experimental period. The MAP of the control group (113 +/- 14 mm Hg) was significantly higher (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 Ki of the cortex ipsilateral to the mannitol injection was increased to 4.5 times that of the contralateral cortex (14.5 +/- 7.7 vs 3.2 +/- 0.6 microL x g(-1) x min(-1); P < 0.002). The Ki of the ipsilateral cortex of the small-dose pentobarbital group was 9.7 +/- 5.6 microL x g(-1) x min(-1). The Ki of the ipsilateral cortex of the large-dose pentobarbital group was 5.5 +/- 2.9 microL x g(-1) x min(-1), and lower (-9.0 microL x g(-1) x min(-1)) than that of the control animals (P < 0.05). There was no significant difference in the Ki of the contralateral cortex among any of the three groups of animals. At the same MAP, the Ki of the ipsilateral cortex of the large-dose pentobarbital group was lower (-4.3 microL x g(-1) x min(-1)) than that of the hydralazine group (9.8 +/- 4.6 microL x g(-1) x min(-1)) (P < 0.05). Pentobarbital attenuated the BBB disruption induced by hyperosmolar mannitol. This may be attributed, at least in part, to the blood pressure effect of pentobarbital.


CONCLUSIONS
When the blood-brain barrier (BBB) was disrupted by a hyperosmolar solution, pentobarbital attenuated 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 be effective in protecting the BBB. Furthermore, systemic blood pressure plays an important role in determining the degree of disruption.
Chi
O Z
OZ
Department of Anesthesia, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, New Brunswick 08901-1977, USA.
Chun
T W
TW
Liu
X
X
Weiss
H R
HR
D000621:Aminoisobutyric Acids / Q000493:pharmacokinetics; D018685:Anesthetics, Inhalation / Q000008:administration & dosage; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D001812:Blood-Brain Barrier / Q000187:drug effects*; D002250:Carbon Radioisotopes; D002339:Carotid Arteries; D002540:Cerebral Cortex / Q000187:drug effects; D004234:Diuretics, Osmotic / Q000009:adverse effects*; D006339:Heart Rate / Q000187:drug effects; D006830:Hydralazine / Q000494:pharmacology; D006993:Hypnotics and Sedatives / Q000008:administration & dosage / Q000494:pharmacology*; D007269:Injections, Intra-Arterial; D007530:Isoflurane / Q000008:administration & dosage; D008297:Male; D008353:Mannitol / Q000009:adverse effects*; D010424:Pentobarbital / Q000008:administration & dosage / Q000494:pharmacology*; D019275:Radiopharmaceuticals; D051381:Rats; D017207:Rats, Sprague-Dawley; D014665:Vasodilator Agents / Q000494:pharmacology
D000621:Aminoisobutyric Acids; D018685:Anesthetics, Inhalation; D000959:Antihypertensive Agents; D002250:Carbon Radioisotopes; D004234:Diuretics, Osmotic; D006993:Hypnotics and Sedatives; D019275:Radiopharmaceuticals; D014665:Vasodilator Agents; C100049:2-aminoisobutyric acid; D006830:Hydralazine; D008353:Mannitol; D007530:Isoflurane; D010424:Pentobarbital