In vitro effects of fentanyl, methohexital, and thiopental on brain endothelial permeability.
BACKGROUND
The use of anesthetics can lead to changes of the permeability of the blood-brain barrier (BBB). To eliminate those factors, such as varying hemodynamic effects that are associated with anesthesia, an in vitro model of the BBB consisting of brain microvascular endothelial cells (BMEC) was used to study the direct effects of the opiate, fentanyl, and the barbiturates methohexital and thiopental, which are widely used in the clinical setting, on the permeability of confluent monolayers.


METHODS
BMEC isolated from porcine brains were grown to confluence on collagen-coated polycarbonate membranes, which were placed into 24 well dishes, thus forming a two-compartment chamber. The permeability of the BMEC monolayer to ions--determined by measurements of the transendothelial resistance (TER)--the passage of sucrose, Evans Blue albumin (EBA), and alpha-aminoisobutyric acid (AIB) across the BMEC monolayer were assessed in the presence and absence of fentanyl (25-100 ng/ml), methohexital (10-50 micrograms/ml), and thiopental (25-100 micrograms/ml).


RESULTS
The permeability of cultured BMEC to the tracers used increased significantly after exposure of the monolayer to arabinose and after removal of calcium ions. Fentanyl, methohexital, and thiopental did not change the permeability of the cell monolayer to ions, sucrose, albumin, and AIB. Only thiopental at the concentration of 100 micrograms/ml increased the flux of AIB.


CONCLUSIONS
At the concentrations tested, there is little evidence of changes in the permeability of the in vitro BBB caused by fentanyl, methohexital, and thiopental regarding the para- and transcellular route of ions, sucrose, and albumin. Only thiopental at a concentration of 100 micrograms/ml increased the passage of AIB across the BMEC monolayer.
Fischer
S
S
Department of Anesthesiology and Intensive Care, Max-Planck Institute for Physiological and Clinical Research, Nauheim, Germany.
Renz
D
D
Schaper
W
W
Karliczek
G F
GF
D000418:Albumins / Q000378:metabolism; D000621:Aminoisobutyric Acids / Q000378:metabolism; D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D004727:Endothelium / Q000187:drug effects; D005283:Fentanyl / Q000494:pharmacology*; D066298:In Vitro Techniques; D008723:Methohexital / Q000494:pharmacology*; D013395:Sucrose / Q000378:metabolism; D013552:Swine; D013874:Thiopental / Q000494:pharmacology*; D013997:Time Factors
D000418:Albumins; D000621:Aminoisobutyric Acids; C100049:2-aminoisobutyric acid; D013395:Sucrose; D008723:Methohexital; D013874:Thiopental; D005283:Fentanyl