Effects of intrathecal verapamil on cerebral vasospasm in experimental rat study

Abstract

Background: Verapamil, a calcium-channel blocker, has shown promising results on cerebral vasospasm. However, it has not yet been accepted for treatment or prevention purposes because of the associated side effects. Although the effective results of nimodipine and nicardipine's intrathecal administration are well known, intrathecal verapamil has not been considered earlier. We used an experimental subarachnoid hemorrhage–induced vasospasm model for the evaluation of vasodilator and neuroprotective effects of intrathecal verapamil. Methods: A total of 24 Sprague-Dawley rats were randomly divided into the following 3 groups: group 1 (sham), group 2 (subarachnoid hemorrhage), and group 3 (verapamil). A double hemorrhage method was used. Group 2 did not receive any treatment. Verapamil (Eporon, Dem Ilac, Turkey) at a dose of 1000 μg/kg was given intrathecally to group 3 rats. The animals were euthanized on day 7 of the procedure. Arterial wall thickness and lumen diameter in the basilar arterial cross-sectional areas, endothelin-1 serum level, oxidative stress index, and apoptosis were measured in all groups. Results: In the verapamil group, wall thickness, endothelin-1 level, oxidative stress index, and apoptosis were found to be significantly lower than the subarachnoid hemorrhage group, but the lumen diameter was found to be greater. Intrathecal verapamil was found to decrease vasospasm parameters and apoptosis and increase the antioxidant and antiapoptotic pathways. Conclusions: Our findings suggest that intrathecal verapamil can prevent vasospasm, oxidative stress, and apoptosis after experimental subarachnoid hemorrhage.