title: Nimodipine does not affect the flow-metabolism couple in permanent cerebral ischemia.
abstract: Despite widespread investigational and clinical usage of the calcium channel blocker nimodipine, its effects on cerebral physiology in normal and ischemic brain remain poorly understood. In order to gain insight into this subject we examined the effects of nimodipine on glucose metabolism and cerebral blood flow-metabolism coupling in the rat during conditions of reproducible focal ischemia. Nimodipine-treated animals were then matched with vehicle-treated controls for both study conditions. Animals were subjected to permanent occlusion of the middle cerebral artery (MCA) along with occlusion of the common carotid arteries. Five minutes into ischemia, an intravenous infusion of nimodipine (1 micro g/kg per min, n=9) or vehicle ( n=9) was initiated and continued until the end of the study. Seventy-five minutes after the occlusion, [14C]2-deoxyglucose was injected into the venous catheter for the measurement of the local cerebral metabolic rate for glucose (LCMRgl), followed 25 min later by the injection of N-isopropyl-[123I] p-iodoamphetamine for the measurement of local cerebral blood flow (LCBF). The animals were killed at the end of 2 h of ischemia, and the brains were processed for double-labeled autoradiography. In all animals, permanent MCA occlusion produced significant decrements in LCBF, LCMRgl, and LCBF/LCMRgl ratio in both the core of the ischemia as well as regions peripheral to the ischemia within the same cerebral hemisphere when compared with non-ischemic brain. There were no significant differences between the nimodipine-treated and vehicle-treated groups. In conclusion, nimodipine does not appear to alter cerebral blood flow or cerebral metabolism in ischemic brain.
authors.affiliation: Cerebrovascular Research Center, Department of Neurology, University of Pennsylvania, 415 Stemmler Hall, 3450 Hamilton Walk, Philadelphia, PA 19104-6063, USA.
authors.forename: Shintaro
authors.initials: S
authors.lastname: Gomi
authors.forename: Mark G
authors.initials: MG
authors.lastname: Burnett
authors.forename: Andrea
authors.initials: A
authors.lastname: Karp
authors.forename: Joel H
authors.initials: JH
authors.lastname: Greenberg
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D002545:Brain Ischemia / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D002121:Calcium Channel Blockers / Q000494:pharmacology / Q000627:therapeutic use; D020746:Calcium Channels, L-Type / Q000187:drug effects / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology; D002536:Cerebral Arteries / Q000187:drug effects* / Q000503:physiopathology; D002560:Cerebrovascular Circulation / Q000187:drug effects* / Q000502:physiology; D004195:Disease Models, Animal; D005947:Glucose / Q000378:metabolism; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D009553:Nimodipine / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D016896:Treatment Outcome
chemical_list: D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D009553:Nimodipine; D005947:Glucose