Effect of remacemide hydrochloride on subarachnoid hemorrhage-induced vasospasm in rabbits

• Published in: Journal of neurotrauma Vol. 11; no. 6; p. 691
• Main Authors: Zuccarello, M, Lewis, A I, Upputuri, S, Farmer, J B, Anderson, D K
• Format: Journal Article
• Language: English
• Published: United States 01-12-1994
• Subjects: Acetamides - pharmacology; Acetamides - therapeutic use; Animals; Anticonvulsants - pharmacology; Anticonvulsants - therapeutic use; Cerebral Angiography; Cerebrovascular Circulation - drug effects; Disease Models, Animal; Ischemic Attack, Transient - diagnostic imaging; Ischemic Attack, Transient - drug therapy; Ischemic Attack, Transient - etiology; Male; Rabbits; Receptors, N-Methyl-D-Aspartate - drug effects; Receptors, N-Methyl-D-Aspartate - physiology; Subarachnoid Hemorrhage - complications; Subarachnoid Hemorrhage - diagnostic imaging; Subarachnoid Hemorrhage - physiopathology
• ISSN: 0897-7151
• DOI: 10.1089/neu.1994.11.691

The purpose of this study was to assess the role of an excitatory amino acid (EAA) receptor antagonist (remacemide hydrochloride) in a rabbit model of subarachnoid hemorrhage (SAH)-induced cerebral vasospasm. Cerebral angiograms were performed on 22 rabbits pre-SAH and 72 h post-SAH: 6 rabbits received an injection of mock cerebrospinal fluid (1 ml/kg) into the cisterna magna (group I, the control group); 6 rabbits were subjected to SAH but received no treatment (group II); autologous blood (1 ml/kg) from the central ear artery was injected into the cisterna magna of these rabbits; 6 rabbits were subjected to SAH (1 ml/kg) and treated with intraperitoneal (IP) bolus injections of remacemide hydrochloride (15 mg/kg) every 12 h beginning 30 minutes after SAH (group III); and 4 rabbits were not subjected to SAH but received IP bolus injections of remacemide hydrochloride every 12 h (group IV). Digital subtraction angiography was used to measure the diameter of the basilar artery. At 72 h post-SAH, vasospasm was evident in all untreated rabbits. The diameter of the basilar artery was reduced significantly below pre-SAH levels by 35.3 +/- 5.8% (mean +/- standard error of the mean). Treatment with remacemide hydrochloride significantly ameliorated vasospasm (27.3 +/- 5.4%, p < 0.001). These findings suggest that in this model EAAs may cooperate in the genesis of SAH-induced cerebral vasospasm and that NMDA receptor antagonism with remacemide hydrochloride can partially prevent the SAH-induced vasospasm of a large cerebral artery.