Efficacy of intrathecal liposomal fasudil for experimental cerebral vasospasm after subarachnoid hemorrhage

OBJECTIVE: To investigate the safety and efficacy of liposomal fasudil in a sustained-release form for the prevention of cerebral vasospasm after suba rachnoid hemorrhage (SAH). METHODS: Eighteen rats were divided into three groups, each of which receiv ed 2.5 mg/kg of liposomal fasudil, 5 mg/kg of liposomal fasudil, or drug-fr ee liposomes after SAH. Next, experimental SAH was induced in 15 dogs by in jection of autologous arterial blood into the cisterna magna twice after ba seline vertebral angiography. In six dogs, 0.94 mg/kg of liposomal fasudil was injected into the cisterna magna (treatment group). In four dogs, drug- free liposomes were similarly injected (placebo group), and the remaining f ive dogs were not treated with liposomal injection after SAH (control group ). Angiography was repeated on Day 7, and cerebrospinal fluid was collected before the dogs were killed. RESULTS: A high dose of liposomal fasudil caused no significant changes in mean arterial blood pressure and did not induce seizures during the observa tion period. Gross and microscopic examination of the brains revealed no ab normalities, but severe vasospasm was noted in the rat basilar artery, main ly in the group treated with drug-free liposomes. Likewise, in the canine p lacebo and control groups, significant vasospasm occurred in the basilar ar tery on Day 7. In the treatment group, vasospasm in the basilar artery was significantly ameliorated (P < 0.01). In vivo, 90% of fasudil was released from liposomes in the cerebrospinal fluid. CONCLUSION: A single injection of intrathecal liposomal fasudil is safe and effective for the prevention of vasospasm in experimental SAH.