title: (S)-emopamil attenuates acute reduction in regional cerebral blood flow following experimental brain injury.
abstract: We examined the effects of (S)-emopamil, a phenylalkylamine calcium channel blocker with serotonin receptor antagonist properties, on regional cerebral blood flow (rCBF) following experimental brain injury in the rat. Animals were subjected to fluid percussion brain injury of moderate severity (2.1 atm), and received (S)-emopamil (20 mg/kg, i.p., n = 10) or saline (n = 10) at 20 minutes postinjury and 2.5 hours after the first injection of the drug. Consecutive rCBF measurements were performed: (1) prior to injury, (2) 15 minutes, (3) 90 minutes, and (4) 4 hours postinjury, using the radiolabeled microsphere technique. Brain injury produced an acute and significant reduction of rCBF at 15 minutes postinjury in all the regions examined (p < 0.05). At 90 minutes postinjury, rCBF remained significantly depressed in the forebrain regions. All brain regions showed a recovery of rCBF to normal by 4 hours following injury in saline-treated animals, with the exception of injured left parietal cortex and bilateral hippocampi, where rCBF remained significantly depressed. A significant attenuation of the trauma-induced reduction in rCBF was observed at 70 minutes after the first administration of (S)-emopamil in the forebrain regions and cerebellum (p < 0.05). Following the second (S)-emopamil injection, the significant improvement in rCBF observed in left injured cortex was maintained. These results suggest that (S)-emopamil may be efficacious in reversing post-traumatic alterations in rCBF, which may contribute to the post-traumatic pathophysiologic sequelae.
authors.affiliation: Division of Neurosurgery, University of Pennsylvania, Philadelphia.
authors.forename: K
authors.initials: K
authors.lastname: Okiyama
authors.forename: T S
authors.initials: TS
authors.lastname: Rosenkrantz
authors.forename: D H
authors.initials: DH
authors.lastname: Smith
authors.forename: T A
authors.initials: TA
authors.lastname: Gennarelli
authors.forename: T K
authors.initials: TK
authors.lastname: McIntosh
mesh_terms: D000818:Animals; D001930:Brain Injuries / Q000503:physiopathology*; D001933:Brain Stem / Q000098:blood supply; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002531:Cerebellum / Q000098:blood supply; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013788:Thalamus / Q000098:blood supply; D014700:Verapamil / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D002121:Calcium Channel Blockers; D014700:Verapamil; C052752:emopamil