title: Hyperglycolysis is exacerbated after traumatic brain injury with fentanyl vs. isoflurane anesthesia in rats.
abstract: Despite common use of narcotics in the clinical management of severe traumatic brain injury (TBI), in experimental models rats treated with fentanyl have exhibited worse functional outcome and more CA1 hippocampal death than rats treated with standard isoflurane anesthesia. We hypothesized that greater post-traumatic excitotoxicity, reflected by cerebral glucose utilization (CMRglu), may account for detrimental effects of fentanyl vs. isoflurane. Rats were anesthetized with either isoflurane (1% by inhalation) or fentanyl (10 mcg/kg iv bolus then 50 mcg/kg/h infusion). 14C-deoxyglucose autoradiography was performed 45 min after controlled cortical impact (CCI) to left parietal cortex (n=4 per anesthetic group) or in uninjured rats after 45 min of anesthesia (n=3 per anesthetic group). Uninjured rats treated with fentanyl vs. isoflurane showed 35-45% higher CMRglu in all brain structures (p<0.05) except CA3. After TBI in rats treated with isoflurane, CMRglu increased significantly only in ipsilateral CA1 and ipsilateral parietal cortex (p<0.05 vs. isoflurane uninjured). Conversely, after TBI in rats treated with fentanyl, CMRglu increased markedly and bilaterally in CA1 and CA3 (p<0.05 vs. fentanyl uninjured), but not ipsilateral parietal cortex. In contralateral CA1, CMRglu was nearly two times greater after TBI in fentanyl vs. isoflurane treated rats (p<0.05). Hyperglycolysis was exacerbated in CA1 and CA3 hippocampus after TBI in rats treated with fentanyl vs. isoflurane anesthesia. This post-traumatic hyperglycolysis suggests greater excitotoxicity and concurs with reports of worse functional outcome and more CA1 hippocampal death after TBI with fentanyl vs. isoflurane anesthesia.
authors.affiliation: Safar Center for Resuscitation Research, University of Pittsburgh School of Medicine, 3434 Fifth Avenue, Pittsburgh, PA 15260, USA.
authors.forename: Kimberly D
authors.initials: KD
authors.lastname: Statler
authors.forename: Keri L
authors.initials: KL
authors.lastname: Janesko
authors.forename: John A
authors.initials: JA
authors.lastname: Melick
authors.forename: Robert S B
authors.initials: RS
authors.lastname: Clark
authors.forename: Larry W
authors.initials: LW
authors.lastname: Jenkins
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Kochanek
mesh_terms: D000758:Anesthesia / Q000009:adverse effects* / Q000379:methods; D000818:Animals; D001930:Brain Injuries / Q000097:blood*; D005283:Fentanyl / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism; D006019:Glycolysis / Q000187:drug effects* / Q000502:physiology; D007530:Isoflurane / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D007530:Isoflurane; D005947:Glucose; D005283:Fentanyl