PURPOSE: Temporary brain ischemia occurring during surgery under general anesthesia may induce the death of neuronal cells and cause severe neurological deficits. On the other hand, it is not clear whether μ-opioid receptor agonists promote ischemic brain injury. It is known that duration of ischemic depolarization affects the degree of neuronal damage. However, the effects of fentanyl during brain ischemia on ischemic depolarization have not been investigated. Therefore, in the current study, the effects of fentanyl on ischemic neuronal damage and ischemic depolarization were quantitatively evaluated. METHODS: Forty-two male gerbils were randomly assigned to a saline-administered group (control group, n = 21) and a fentanyl-administered group (fentanyl group, n = 21). Fentanyl at 50 μg/kg was first administered over a 10-min period and then 50 μg/kg/h was administered continuously for the fentanyl group. Forebrain ischemia was initiated by occlusion of bilateral common carotid arteries and sustained for 3, 5, or 7 min (n = 7 in each group). Direct-current potentials were measured in bilateral CA1 regions, in which histological evaluation was performed 5 days later. RESULTS: There were no significant differences in onset time, duration of ischemic depolarization, and percentage of neuronal damage between the two groups with any ischemic duration. In the relationships between ischemic time and neuronal damage and those between duration of ischemic depolarization and neuronal damage, there was no significant difference in the percentage of neuronal damage between the two groups. CONCLUSION: Fentanyl at a clinically relevant dose does not affect ischemic depolarization and ischemic neuronal damage.
PURPOSE: Temporary brain ischemia occurring during surgery under general anesthesia may induce the death of neuronal cells and cause severe neurological deficits. On the other hand, it is not clear whether μ-opioid receptor agonists promote ischemic brain injury. It is known that duration of ischemic depolarization affects the degree of neuronal damage. However, the effects of fentanyl during brain ischemia on ischemic depolarization have not been investigated. Therefore, in the current study, the effects of fentanyl on ischemic neuronal damage and ischemic depolarization were quantitatively evaluated. METHODS: Forty-two male gerbils were randomly assigned to a saline-administered group (control group, n = 21) and a fentanyl-administered group (fentanyl group, n = 21). Fentanyl at 50 μg/kg was first administered over a 10-min period and then 50 μg/kg/h was administered continuously for the fentanyl group. Forebrain ischemia was initiated by occlusion of bilateral common carotid arteries and sustained for 3, 5, or 7 min (n = 7 in each group). Direct-current potentials were measured in bilateral CA1 regions, in which histological evaluation was performed 5 days later. RESULTS: There were no significant differences in onset time, duration of ischemic depolarization, and percentage of neuronal damage between the two groups with any ischemic duration. In the relationships between ischemic time and neuronal damage and those between duration of ischemic depolarization and neuronal damage, there was no significant difference in the percentage of neuronal damage between the two groups. CONCLUSION:Fentanyl at a clinically relevant dose does not affect ischemic depolarization and ischemic neuronal damage.
Authors: J Cory Kalvass; Emily R Olson; Michael P Cassidy; Dana E Selley; Gary M Pollack Journal: J Pharmacol Exp Ther Date: 2007-07-23 Impact factor: 4.030