Cilostazol attenuates cerebral vasospasm after experimental subarachnoid hemorrhage.

Background and Purpose: Cerebral vasospasm is a major cause of morbidity and mortality in patients with subarachnoid hemorrhage (SAH). Cilostazol, a selective inhibitor of phosphodiesterase 3, is a peripheral vasodilator, an anti-inflammatory, and causes antiplatelet aggregation. We investigated these effects on cerebral vasospasm after rat SAH.
Methods: Thirty-eight Sprague-Dawley rats were randomly divided into three groups: SAH + normal feed (SAH group; n=14), SAH + feed containing 0·1% cilostazol (cilostazol group; n=12) and sham-operated rats (sham group; n=12). The basilar arteries (BA) of all groups were analysed by measuring wall thickness, internal luminal perimeter and cross-sectional area on day 7. Immunohistochemical study with RM-4, an anti-rat macrophage/dendritic cells monoclonal antibody and ultrastructural study with transmission electron microscopy were performed.
Results: Although most animals in the SAH group presented with typical vasospasm, the means of inner perimeter and cross-section area of the BA in the cilostazol group were significantly greater than the SAH group (836 ± 134 μm versus 771 ± 125 μm and 39 177 ± 15 405 μm(2) versus 33 098 ± 13 871 μm(2), respectively). Wall thickness of the BA in the cilostazol group demonstrated significant decrease, compared with the SAH group (17·4 ± 2·3 versus 21·0 ± 2·7 μm). In immunohistological study, SAH induced an obvious increase in mean perivascular RM-4-positive cell count, whereas cilostazol significantly reduced it by 59%. Ultrastructural study depicted cilostazol markedly attenuating structural deterioration of the vascular wall due to SAH.
Conclusions: This work demonstrates that cilostazol attenuates cerebral vasospasm after SAH in rat, possibly in part due to the anti-inflammatory effect.