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Alfentanil-Induced Hypermetabolism, Seizure, and Histopathology in Rat Brain

Departments of Anesthesiology and Critical Care Medicine and Neurological Surgery, Neurologic Anesthesia and Supportive Care Program, and Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania; and Department of Physiology and Biophysics, University of Health Sciences, The Chicago Medical School, Chicago, Illinois

Abstract

We evaluated the effect of alfentanil on hippocampal glucose utilization and histopathology associated with alfentanil-induced seizures. Three separate experiments were performed. First, anesthetized, paralyzed Long-Evans rats (n = 15; 5 rats per group) were mechanically ventilated and randomly assigned to three groups: (a) control, 70% N₂O and 30% O₂continued for 1 h; (b) low-dose alfentanil (150 µg/kg IV bolus), followed by infusion at 15 µg.kg^–1.min^–1 for 1 h without N₂O; or (c) high-dose alfentanil (1000 µg/kg IV bolus), followed by infusion at 100 µg.kg^–1.min^–1 for 1 h without N₂O. After 1 h, [6-¹⁴C]glucose was injected intravenously for autoradiography. With high-dose alfentanil, there was increased glucose utilization in the ventral hippocampus and the lateral septal nucleus. In the second experiment, anesthetized, paralyzed Sprague-Dawley rats (n = 12; 4 rats per group) were mechanically ventilated, underwent insertion of hippocampal depth electrodes, and were randomly assigned to three groups: (a) control, 70% N₂O and 30% O₂;(b) low-dose alfentanil (150 µ/kg IV bolus), with 70% N₂O and 30% O₂; or (c) high-dose alfentanil (1000 µg/kg IV bolus), with 70% N₂O and 30% O². An epileptiform pattern was observed on hippocampal and subdermal electroencephalographic recordings in both alfentanil groups. In the third experiment, anesthetized, paralyzed Sprague-Dawley rats (n = 20) were mechanically ventilated and assigned to two groups: (a) control, 70% N₂O and 30% O₂ (n = 5) or 100% O₂ (n = 5) continued for 1 h; or (b) alfentanil (2000 µg/kg IV bolus), followed by infusion at 33.3 µg.kg^–1.min^–1 for 1 h with 100% O₂. After tracheal extubation, the rats recovered overnight. Light-microscopic evaluation revealed hippocampal or amygdaloid damage in 6 of the 10 alfentanil-treated rats. High doses of alfentanil administered to rats can produce limbic system seizure activity with hypermetabolism associated with neuropathologic lesions.

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