Delayed administration of the K+ channel activator cromakalim attenuates cerebral vasospasm after experimental subarachnoid hemorrhage

Background. Delayed cerebral vasospasm remains an unpredictable and inadequately treated complication of aneurysmal subarachnoid hemorrhage (SAH). Recent evidence indicates that the potassium channel activator cromakalim is capable of limiting cerebral vasospasm in rabbits when administered immediately after experimental SAH (i.e. before spastic constriction has been initiated). However, the ultimate clinical value of cromakalim for treating vasospasm will depend in pat? on its effectiveness when administered after SAM-induced constriction has already been initiated. The present study examined the effects of cromakalim on vasospasm when treatment was initiated after SAM-induced constriction was underway. Methods. New Zealand whits rabbits were subjected to experimental SAH by injecting autologous blood into the cisterna magna. Cromakalim (0.03, 0.1 or 0.3 mg/kg) or vehicle was injected intravenously at 8 hour intervals beginning 24 hours post-SAM. Animals were killed by perfusion fixation 48 hours after SAM. Basilar arteries were removed and sectioned, and cross-sectional area was measured. Findings. The average cross sectional areas of basilar arteries were reduced by 64% and 68% in the SAM-only and SAH + vehicle groups, respectively. Treatment with cromakalim dose-dependently attenuated SAM-induced constriction. The groups treated with 0.03, 0.1, and 0.3 mg/kg cromakalim exhibited average decreases in cross-sectional area of 57%, 42%, and 19%, respectively. Interpretation. These findings indicate that cromakalim dose-dependently attenuates cerebral vasospasm when administered 24 hours after experimental SAH in the rabbit. The results suggest K-ATP channel activators, such as cromakalim, could be of benefit for reversing cerebral vasospasm after aneurysmal SAH.