The potential use of nicardipine in cerebrovascular disease.
The efficacy of intravenous nicardipine in the prevention of vasospasm after subarachnoid hemorrhage has been investigated in a dose escalation study in 67 patients admitted within 1 week of subarachnoid hemorrhage. Favorable outcomes were noted in 52 patients (78%). Vasospasm was found by arteriography in 31 patients (46%). A dose-related trend was noted. At the lower dose levels, angiographic spasm was observed in 68% and symptomatic vasospasm in 27% of 34 patients. Only eight of 33 patients (24%) treated at the highest dose level (approximately 10 mg/hr) developed arteriographic evidence of vasospasm. Symptomatic vasospasm was diagnosed in only two of 33 patients (6%) treated with this dose. No deaths from vasospasm occurred. Verification of changes in tissue calcium has been obtained from the rat middle cerebral artery occlusion model, and we concluded that nicardipine administered after permanent occlusion may offer protection against cerebral ischemia in this animal model. Nicardipine uptake was greater at the infarct site than in surrounding tissue, with the highest concentration in the area of maximal ischemia. Nicardipine appears to affect changes in Ca2+ more than other ions: it significantly reduced Ca2+ accumulation in the territory of the middle cerebral artery by 60% at 6 hours, and significantly reduced Na+ and K+ shifts in the same territory by 40% and 50%, respectively, at 6 hours. Although much research remains to be done, a wide role for the dihydropyridines in a number of cerebrovascular conditions is emerging.
Flamm
E S
ES
Division of Neurosurgery, University of Pennsylvania, Philadelphia 19104.
D000818:Animals; D001834:Body Water / Q000378:metabolism; D001921:Brain / Q000378:metabolism; D002545:Brain Ischemia / Q000188:drug therapy* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D006801:Humans; D002546:Ischemic Attack, Transient / Q000188:drug therapy* / Q000209:etiology; D009529:Nicardipine / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011188:Potassium / Q000378:metabolism; D051381:Rats; D012964:Sodium / Q000378:metabolism; D013345:Subarachnoid Hemorrhage / Q000150:complications
D012964:Sodium; D009529:Nicardipine; D011188:Potassium; D002118:Calcium