Therapeutic Effect of a New Immunosuppressant, FK-506, on Vasospasm after Subarachnoid Hemorrhage

Abstract

We hypothesized that the immunological reaction against extravasated blood might play a role in the development of vasospasm after subarachnoid hemorrhage. Under the hypothesis, we had reported significant therapeutic efficacy of cyclosporin A on vasospasm in canine models. We here investigated the efficacy of a new, potent immunosuppressant, FK-506, on vasospasm in animal models. Dogs were randomly classified into sham operated, subarachnoid hemorrhage treated-1 group, (FK-506, 0.3 mg/kg-d, intramuscular injection), and treated-2 group (FK-506, 0.15 mg/kg-d, intramuscular injection). Levels of the third factor of complement (C3) and the activity of serum complement inducing 50% hemolysis of sheep erythrocytes (CH50) in serum were also determined. In the treated groups, the levels of FK-506 in serum were monitored. As for C3 and CH50, there were no statistically significant differences among the groups and there were no changes between Day 1 and Day 7 in any group. Angiographical diameters of a basilar artery on Days 1 and 7 were measured with a computed image analyzer, and the extent of vasospasm was compared among the groups. Statistically significant differences between the sham-operated group and the other three groups were noted. However, under sufficient levels of FK-506 in serum, the extent of vasospasm in either treated group was the same as that in the subarachnoid hemorrhage group. These results indicate a significant discrepancy in the therapeutic mechanism for vasospasm between cyclosporin A and FK-506. They have common aspects in the immunosuppressive mechanism. However, in T-cell suppression, the different mechanism in situ between the two drugs is also postulated.(ABSTRACT TRUNCATED AT 250 WORDS)