PURPOSE: Spinal cord ischemia and resulting paraplegia represent a major 
complication associated with surgical repair of the thoracoabdominal aorta. 
Although the mechanism of spinal neuronal degeneration during ischemia is 
unclear, it may involve excessive calcium influx via N-type voltage-sensitive 
calcium channels (VSCCs). The neuroprotective capacity of intrathecal (IT) 
administration of the selective N-type VSCC blocker ziconotide, previously shown 
to be potently analgesic, was studied.
METHODS: In a rat aortic occlusion model, spinal cord ischemia was induced for 
8, 9, or 10 minutes by occluding the descending thoracic aorta. Ziconotide was 
administered IT as (1) a continuous infusion of 300 or 600 ng/kg/h initiated 24 
hours before ischemia and continuing an additional 24 hours or (2) a 0.3 
microgram bolus injected 45 minutes before the induction of ischemia. Animals 
were allowed to live for 24 hours, and recovery of motor function was evaluated 
during this period. Spinal cords were processed using a silver impregnation 
technique and microtubule-associated protein type II (MAP2) 
immunohistochemistry.
RESULTS: Continuous IT infusion of ziconotide provided significant protection 
against 8- and 9-minute occlusions, but not 10-minute occlusions, as indicated 
by recovery of motor function, degree of spinal neuronal degeneration, and loss 
of MAP2 immunoreactivity. Acute IT pretreatment with ziconotide provided 
transient protection during the initial 4 hours of reperfusion; however, this 
protective effect was no longer present at 24 hours.
CONCLUSION: These data implicate N-type VSCC activation in spinal neuronal 
degeneration caused by transient spinal ischemia, because selective blockade of 
this channel by continuous IT infusion of ziconotide was protective against 
injurious intervals of spinal ischemia. Based on these findings, ziconotide may 
provide both neuroprotection and preemptive analgesia for aortic aneurysm 
surgery.