Effects of Fentanvl on a-Aminoisobutvric Acid Transfer Across the Blood-Brain Barrier Oak Za Chi, m, Hwu Meei Wei, PhD, Mujahid Anwar, m, Arabinda K. Sinha, PhD, Sanford L. Hein, DDS, m, and Harvey R. Weiss, PhD Departments of Anesthesia, Pediatrics, and Physiology and Biophysics, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, New Brunswick, New Jersey The effect of fentanyl on the transfer of small hydro- philic molecules across the blood-brain barrier was studied in rats by measuring the blood-brain transfer coefficient (4) and the regional cerebral blood flow (KBF) and by calculating the capillary permeability- surface area product. In the control group (n = 14), after a femoral artery and vein were catheterized under isoflurane anesthesia, the rats were allowed to remain awake for 1.5 h before measuring & (n = 8) using intravenous '4C-cr-aminoisobutyric acid or KBF (n = 6) using ''C-iodoantipyrine. In the fenta- nyl groups, rats were injected with 25 pgkg (low dose) (n = 6) or 100 pgkg (high dose) of fentanyl (n = 14), followed b a continuous infusion at a rate of 50 or 200 pgkg-rh-', respectively. Their lungs were mechanically ventilated. The & (low dose, n = 6; high dose, n = 8) and rCBF (high dose, n = 6) were measured 1 h after fentanyl infusion. The K, was lower in 9 of 13 brain regions in the low-dose fentanyl group and in 7 of 13 brain regions in the high-dose fentanyl group than in the control animals. The average value of & in all the brain regions was 8.6 ? 4.6 pL.g-'.min-' in the control group, 5.2 ? 2.9 FL.g-'.min-' in the low-dose fentanyl group, and 5.7 2 2.9 pL.g-'.min-' in the high-dose fentanyl group. High-dose fentanyl did not significantlyaffect KBF in any brain region studied. The value of the regional permeability-surface area product was simi- lar to the corresponding regional K, in the groups studied. In conclusion, fentanyl decreased the trans- fer of small hydrophilic molecules across the blood- brain barrier, as demonstrated by a decreased K, and permeability-surface area product, without signif- cant changes in KBF. (Anesth Analg 1992;75:31-6) he blood-brain barrier (BBB) is an anatomic and functional structure that plays an important T role in maintaining the homeostasis of the brain. An intact BBB is required to protect the brain against various circulating molecules and neurotoxins in the plasma (1,2). The characteristic property of the BBB may be changed with osmotic agents (3), sudden hypertension, extreme hypotension with the use of vasodilating agents (4,5), trauma, inflammation, an- oxia, and seizures (6). Recently, saija et al. (7) demonstrated that both pentobarbital and ketamine decreased the transfer of small hydrophilic molecules across the BBB even though ketamine increased cerebral glucose utiliza- This work was supported by grants from the American Heart Association, New Jersey Affiliate (89-021, 90-014) and the UNted States public Health Service (NS25100). Accepted for publication March 16,1992. Addreas correspondence to Dr. Chi, Department of Anesthesia, UNversity of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, CN 19, One Robert Wood JohnsonPlace, New Brunswick, NJ 08903-0019. tion. Our previous study (8) showed that the blood- brain transfer coefficient (&) for small hydrophilic molecules was decreased under isoflurane anesthe- sia. We hypothesized that the transfer of these sub- stances across the BBB would also be decreased during fentanyl administration because both are an- esthetic and lipophilic agents. In our study, the effect of fentanyl on & was measured using 'T-a-aminoisobutyric acid ('%-AIB). a-Aminoisobutyric acid is a small, synthetic, inert neutral amino acid with a molecular mass of 104 daltons that does not cross the BBB rapidly (9). Once it does cross, however, it is quickly absorbed and concentrated in the brain cells. Its backflux into blood is minimized (10). Therefore, transfer across the BBB is the rate-determining factor in the accumulation of AIB in brain cells. Regional cerebral blood flow (rCBF) was determined using 'v-iodoantipyrine. The ex- traction fraction and the capillary permeability- surface area product were calculated from ICBF and Y- Q1992 by the Intemational Anesthesia Research Sodety 0003-2999/9(US5.00 Anesth Analg 1992;75314 31