Effects of protease inhibitor and immunosuppressant on cerebral vasospasm after subarachnoid hemorrhage in rabbits.

The possible role of the immune-defense system in the development of cerebral vasospasm after subarachnoid hemorrhage (SAH) was investigated in rabbits. We used a synthetic serine protease inhibitor, gabexate mesilate (GM), a glucocorticoid, betamethasone sodium phosphate (B-P), and an immunosuppressant, ciclosporin (Cyclosporin A, CYA), to prevent cerebral vasospasm. These agents were administered intra-venously every 12 hours for three injections, starting 20 minutes after SAH. In the group treated with GM, B-P, or CYA, there were no statistically significant differences in arterial calibers between treated and untreated controls on day 2. The synthetic serine protease inhibitor, FUT-175 has been reported to prevent cerebral vasospasm when the treatment is started 20 minutes after SAH in rabbits [38]. In rabbits treated with FUT-175 at different starting times from 3 to 6 hours, reductions in arterial caliber on day 2 were significantly prevented in each group. The contrasting effects of the two serine protease inhibitors, GM and FUT-175, are discussed.