OBJECTIVE: Local intra-arterial infusions of verapamil and nicardipine have been used to treat human cerebral vasospasm. Only a few reports of early clinical experience with these medications are currently available, and limited data are available regarding their cerebral physiological activity. We assessed the efficacy of intracarotid administration of verapamil and nicardipine on augmenting cerebral blood flow of New Zealand White rabbits and compared the ability of these drugs with reverse topical endothelin (ET)-1-triggered vasospasm. METHODS: In the first group of New Zealand white rabbits, cerebral blood flow (laser Doppler) and systemic hemodynamic measurements were recorded at baseline and with increasing intracarotid doses of verapamil and nicardipine. In the second group, topical ET-1 (10(-4) mol/L) was applied in an acutely implanted cranial window. Dose responses to nonspecific reversal of ET-1-induced vasospasm were evaluated with intra-arterially administered nicardipine and verapamil. RESULTS: The dose-response studies revealed that intracarotid administration of nicardipine, compared with verapamil, was more effective in augmenting cerebral blood flow. Topical ET-1-induced vasospasm was completely reversed by nicardipine and partially reversed by verapamil. CONCLUSION: This study suggests that intra-arterially administered nicardipine is a more potent cerebral vasodilator and is superior to verapamil for treating ET-1-induced experimental cerebral vasospasm and supports further investigation of these agents in subarachnoid hemorrhage-induced vasospasm.
OBJECTIVE: Local intra-arterial infusions of verapamil and nicardipine have been used to treat humancerebral vasospasm. Only a few reports of early clinical experience with these medications are currently available, and limited data are available regarding their cerebral physiological activity. We assessed the efficacy of intracarotid administration of verapamil and nicardipine on augmenting cerebral blood flow of New Zealand White rabbits and compared the ability of these drugs with reverse topical endothelin (ET)-1-triggered vasospasm. METHODS: In the first group of New Zealand white rabbits, cerebral blood flow (laser Doppler) and systemic hemodynamic measurements were recorded at baseline and with increasing intracarotid doses of verapamil and nicardipine. In the second group, topical ET-1 (10(-4) mol/L) was applied in an acutely implanted cranial window. Dose responses to nonspecific reversal of ET-1-induced vasospasm were evaluated with intra-arterially administered nicardipine and verapamil. RESULTS: The dose-response studies revealed that intracarotid administration of nicardipine, compared with verapamil, was more effective in augmenting cerebral blood flow. Topical ET-1-induced vasospasm was completely reversed by nicardipine and partially reversed by verapamil. CONCLUSION: This study suggests that intra-arterially administered nicardipine is a more potent cerebral vasodilator and is superior to verapamil for treating ET-1-induced experimental cerebral vasospasm and supports further investigation of these agents in subarachnoid hemorrhage-induced vasospasm.