HIGH-DOSE FENTANYL DOES NOT ADVERSELY AFFECT OUTCOME FROM FOREBRAIN ISCHEMIA IN THE RAT

Fentanyl citrate has properties, including agonism of the mu-opioid re ceptor and proconvulsant activity, that theoretically could pose adver se effects in ischemic brain. This study examined the effects of high- dose fentanyl on outcome in rats subjected to transient near-complete forebrain ischemia. Rats were anesthetized with halothane and surgical ly prepared for ischemia. In one group (fentanyl; n = 15), intravenous fentanyl (400 mu g/kg followed by an infusion of 16 mu g/kg/min for 2 0 min) was administered and halothane was discontinued. In the remaini ng rats (control: n = 15), halothane administration was continued and no fentanyl was given. Following 10 min of bilateral carotid artery oc clusion and profound systemic hypotension, animals were maintained nor mocapnic, normothermic, and mildly hyperoxemic for 8 h. Four days late r, histologic and neurologic outcomes were assessed. In another group of rats also administered halothane (uncontrolled recovery, n = 15), n o attempt was made to control physiologic variables during recovery fr om ischemia. Fentanyl caused preischemic evidence of epileptoid activi ty but decreased the percentage of neurons that died in the CA(1) sect or of the hippocampus relative to control (p = 0.0005). Damage in the cortex or caudoputamen was not different from that in the control grou p. Rats with an uncontrolled recovery had decreased damage in the cort ex (p = 0.005) and caudoputamen (p = 0.00015) relative to control. In this model of forebrain ischemia, fentanyl caused no worsening of hist ologic damage in the cortex or caudoputamen and decreased hippocampal CA(1) injury despite major electroencephalographic activation in the i mmediate preischemic period.