Effect of combined simvastatin and cyclosporine compared with simvastatin alone on cerebral vasospasm after subarachnoid hemorrhage in a canine model.
OBJECTIVE
The object of this study was to determine whether the combination of cyclosporine and simvastatin could ameliorate cerebral vasospasm after subarachnoid hemorrhage (SAH) in a canine model to a greater extent than simvastatin alone.


METHODS
Animals were assigned to one of three groups: control (five dogs), simvastatin alone (four), or simvastatin and cyclosporine (four). A double SAH model was used. Baseline basilar artery (BA) angiograms were obtained. These were repeated at Days 3, 7, and 10. Measurement of the BA diameter was performed. Decreased BA diameter was seen on Day 3 in the control and simvastatin/cyclosporine group. A return to baseline diameters was seen by Day 7. An increase from baseline diameter was seen in the simvastatin group at Day 10.


CONCLUSIONS
Cyclosporine may interfere with the vasodilatory effects of simvastatin. Vasodilation greater than baseline is seen at Day 10 in the simvastatin group. The combination of simvastatin and cyclosporine does not ameliorate cerebral vasospasm in a canine model to a greater extent than simvastatin alone.
Bulsara
Ketan R
KR
Division of Neurosurgery and Department of Radiology, University of Missouri-Columbia, Columbia, Missouri, USA. ketanbulsara@hotmail.com
Coates
Joan R
JR
Agrawal
Vivek K
VK
Eifler
Danielle M
DM
Wagner-Mann
Colette C
CC
Durham
H Edward
HE
Fine
Deborah M
DM
Toft
Kris
K
D000704:Analysis of Variance; D000792:Angiography / Q000379:methods; D000818:Animals; D001488:Basilar Artery / Q000187:drug effects / Q000473:pathology; D016572:Cyclosporine / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004285:Dogs; D004359:Drug Therapy, Combination; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D011897:Random Allocation; D019821:Simvastatin / Q000627:therapeutic use*; D013345:Subarachnoid Hemorrhage / Q000150:complications; D013997:Time Factors; D020301:Vasospasm, Intracranial / Q000188:drug therapy* / Q000209:etiology
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D019821:Simvastatin