Opioid neurotoxicity: fentanyl-induced exacerbation of cerebral ischemia in rats

• Published in: Brain research Vol. 818; no. 2; pp. 326 - 334
• Main Authors: Kofke, W.Andrew, Garman, Robert H, Garman, Rosalyn, Rose, Marie E
• Format: Journal Article
• Language: English
• Published: London Elsevier B.V 13.02.1999; Amsterdam Elsevier; New York, NY
• Subjects: Analgesics, Opioid - toxicity; Analysis of Variance; Anesthetic; Animals; Biological and medical sciences; Brain Ischemia - chemically induced; Brain: ischemia, hypoxia, neuropathology, seizure; Dose-Response Relationship, Drug; Drug toxicity and drugs side effects treatment; Fentanyl - toxicity; Intravenous: fentanyl; Male; Medical sciences; Neurotoxins - toxicity; Pharmacology. Drug treatments; Rats; Rats, Sprague-Dawley; Toxicity: nervous system and muscle; Treatment Outcome; Anesthetic; Intravenous: fentanyl; Brain: ischemia, hypoxia, neuropathology, seizure; Nervous system diseases; Rat; Toxicity; Rodentia; Fentanyl; Cardiovascular disease; Opiates; Narcotic analgesic; Cerebral disorder; Vascular disease; Vertebrata; Experimental disease; Mammalia; Ischemia; Animal; Central nervous system disease; Cerebrovascular disease; Brain (vertebrata)
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/S0006-8993(98)01228-1

We tested the hypothesis that fentanyl would worsen ischemia-induced brain damage. In two sequential protocols forty rats were physiologically monitored and controlled. In protocol 1, rats were randomized ( n=10/group) to 30 min of control (N 2O plus 0.4% halothane), low dose fentanyl (loading dose [LD] 50 μg kg −1, maintenance dose [MD] 2 μg kg −1 min −1), or high-dose fentanyl (LD 800 μg kg −1, MD 32 μg kg −1 min −1). After 15 min of fentanyl or sham infusion trimethaphan 0.5 mg was given i.v. and 3 min later bilateral carotid artery occlusion and blood withdrawal-induced hypotension were maintained for 12 min. At 18 h postischemia rats underwent cerebral perfusion fixation. Brain areas were graded from 0 (normal) to 5. In addition to analysis of specific regions, neuropathologic scores were also summated over all brain regions and analyzed to compute a summed neuropathologic score. In protocol 2, five control and five high-dose fentanyl rats were treated identically except that post-ischemic oxygenation was maintained for 6 h and cerebral perfusion-fixation was performed 6 h post-ischemia. Only the caudate/putamen was examined in protocol 2. Fentanyl worsened lesions in both fentanyl groups' summed neuropathologic scores ( P=0.002) in protocol 1 and specifically, in the caudate/putamen ( P<0.01) in both protocols. Fentanyl in both high and low doses can exacerbate incomplete forebrain ischemia in rats.