Systemic administration of the potassium channel activator cromakalim attenuates cerebral vasospasm after experimental subarachnoid hemorrhage

OBJECTIVE: Cerebral vasospasm is a primary complication after aneurysmal subarachnoid hemorrhage (SAH). Recent evidence indicates that the activation of potassium (K(+)) channels may be of benefit in relieving spastic constriction. The present study examined the effects of systemic administration of a K(+) channel activator, cromakalim, on cerebral vasospasm after experimental SAH. METHODS: Experimental SAH was performed in rabbits by injecting autologous blood into the cisterna magna. Intravenous injections of cromakalim or vehicle were administered twice daily with the first injection administered 1 hour after induction of SAH. Animals were killed by perfusion-fixation 48 hours after SAH. Basilar arteries were removed and sectioned, and the luminal cross-sectional areas were measured. RESULTS: Experimental SAH induced cerebral vasospasm in untreated and vehicle-treated animals. Cromakalim attenuated cerebral vasospasm in a dose-dependent manner. This effect achieved statistical significance at doses of 0.1 and 0.3 mg/kg. CONCLUSION: These results support the concept that targeting vascular K(+) channels can be of benefit in preventing the development of cerebral vasospasm. The findings also indicate that cromakalim represents a potential therapeutic agent for the treatment of cerebrovascular pathophysiology after SAH.