EFFECTS OF ISOFLURANE ON TRANSPORT ACROSS THE BLOOD-BRAIN-BARRIER

The blood-brain barrier (BBB) plays an important role in regulating and restricting transfer of molecules into the interstitial space of the brain. Anesthetic agents may affect the permeability of the BBB. In this investigation, the effect of isoflurane on the transport of small hydrophilic molecules across the BBB was studied in rats by measuring the blood-brain transfer coefficient (Ki) and the regional cerebral blood flow (rCBF) and by calculating the capillary permeability-surface area (PS) product. In the control group, after a femoral artery and vein were catheterized under isoflurane anesthesia, rats were allowed to remain awake for 2 h before measuring Ki (n = 6) or rCBF (n = 11). In the two experimental groups, rats were anesthetized with 1% and 2% isoflurane respectively, and their lungs were mechanically ventilated through a tracheal tube. Ki was measured (1% n = 6, 2% n = 7) using C-14-alpha-aminoisobutyric acid, and rCBF was measured (2% n = 7) using C-14-iodoantipyrine. Two percent isoflurane did not affect rCBF in 9 of 13 brain regions. Blood flow was less in the lateral and posterior cortex and greater in the medulla and pons when compared with the control group. Ki was less in 11 of 13 brain regions in both the 1% and 2% isoflurane groups than in the control group. There was no significant difference between 1 and 2% isoflurane in any brain region. The average values of Ki in all of the brain regions were 8.9 +/- 4.9-mu-l . g-1 . min-1 in the control group and 4.6 +/- 2.6 and 5.1 +/- 3.4 mu-l . g-1 . min-1 in the 1% and 2% isoflurane groups, respectively (P < 0.0001). The PS product was similar to Ki in the groups studied. In conclusion, isoflurane anesthesia decreased the transport of small hydrophilic molecules across the BBB, as was demonstrated by decreases in Ki and the PS product without large changes in rCBF.