Nimodipine and chronic vasospasm in monkeys: Part 1. Clinical and radiological findings.
The efficacy of the calcium channel blocker nimodipine in the prevention of chronic cerebral vasospasm (VSP) and delayed ischemia after subarachnoid hemorrhage (SAH) in monkeys was examined in a blind, randomized, placebo-controlled trial. The primate model developed in this laboratory reliably induces chronic cerebral vasospasm and can induce pathologically proven delayed ischemic neurological deficits (DINDs). With standard microsurgical procedures, an average 6.4-ml autologous hematoma was placed directly against the major anterior cerebral vessels in the right basal subarachnoid spaces of 24 monkeys. The monkeys were randomized to one of four groups and were treated orally q8h for 7 days with nimodipine (3, 6, or 12mg/kg)or placebo. An additional 2 monkeys underwent the surgical procedure without clot placement. Drug administration began between 14 and 20 hours after clot placement. Indices monitored before and after SAH included neurological status, angiographic cerebral vessel caliber, and cerebral blood flow. Significant VSP (25 to 100% reduction in vessel caliber) was present on Day 7 on the clot side in 83% of the animals (P less than or equal to 0.001). There was no significant difference (P greater than 0.05) in the incidence of VSP among the four groups. Similarly, there was no significant difference (P greater than 0.05) in the mean vessel caliber reduction after SAH among the four treatment groups. There was no VSP present on Day 7 in the sham-operated animals. One animal receiving high dose nimodipine (12 mg/kg p.o. q8h) developed a DIND on Day 5 after SAH. A second animal in the 12-mg/kg group developed a transient neurological deficit between Days 4 and 7.
D000818:Animals; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D004195:Disease Models, Animal; D005260:Female; D002546:Ischemic Attack, Transient / Q000517:prevention & control*; D008252:Macaca fascicularis; D009539:Nicotinic Acids / Q000008:administration & dosage / Q000627:therapeutic use*; D009553:Nimodipine; D013345:Subarachnoid Hemorrhage / Q000188:drug therapy*
D002121:Calcium Channel Blockers; D009539:Nicotinic Acids; D009553:Nimodipine