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.


CONCLUSIONS
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.
Kwan
A L
AL
Department of Neurological Surgery, University of Virginia, Charlottesville 22908, USA.
Lin
C L
CL
Yanamoto
H
H
Howng
S L
SL
Kassell
N F
NF
Lee
K S
KS
D000818:Animals; D001488:Basilar Artery / Q000187:drug effects / Q000473:pathology; D019806:Cromakalim / Q000008:administration & dosage / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D007275:Injections, Intravenous; D002546:Ischemic Attack, Transient / Q000188:drug therapy* / Q000209:etiology* / Q000473:pathology; D008297:Male; D015221:Potassium Channels / Q000819:agonists*; D011817:Rabbits; D013345:Subarachnoid Hemorrhage / Q000150:complications*
D015221:Potassium Channels; D019806:Cromakalim