Effects of fentanyl on local cerebral blood flow in the rat

Fentanyl reduces the cortical cerebral blood flow and metabolic rate for oxygen in rats, though seizure activity occurs in some animals at high doses. However, the effects of fentanyl on blood flow and metabolism in subcortical structures have not been clearly delineated. The present study examines the effects of intravenous fentanyl (100 or 400 micrograms . kg-1) on local cerebral blood flow (1-CBF) in paralyzed, mechanically ventilated rats. Rats ventilated with 70% N2O in 30% O2 served as controls. Local CBF was measured using 14C-iodoantipyrine and autoradiography. Blood pressure, PaO2, PaCO2, pH, and temperature were comparable in all groups. The EEG showed slow wave activity in most animals given 100 micrograms . kg-1 fentanyl while seizure activity occurred in all animals given 400 micrograms . kg-1 fentanyl. With 100 micrograms . kg-1 fentanyl, CBF tended to be depressed in all cortical and subcortical areas, except the peri-aqueductal gray; and with 400 micrograms . kg-1 fentanyl, 1-CBF tended to be elevated (compared to 100 micrograms . kg-1 fentanyl) in most areas of the brain. The limbic system structures, however, were most affected by 400 micrograms . kg-1 fentanyl with statistically significant increases (compared to the 100 micrograms . kg-1 group) in 1-CBF of 86% and 67% respectively in the amygdala and septal nucleus. These results confirm that moderately high doses of fentanyl which cause slow wave activity on the EEG also depress 1-CBF in rats; moreover, doses of fentanyl that produce seizure activity produce increases in 1-CBF in most cerebral structures with greatest effects on limbic system 1-CBF.