24. RETROGRADE VENOUS PERFUSION OF A SODIUM CHANNEL ANTAGONIST PROVIDES SPINAL CORD PROTECTION DURING PERIODS OF PROLONGED AORTIC CROSSCLAMPing
James J. Gangemi, John A. Kern, Irving L. Kron*, Scott D. Ross, Curtis G. Tribble*
University of Virginia Health Sciences Center
Charlottesville, Virginia, USA
OBJECTIVE
Neuronal voltage-dependent sodium channel (NVSC) antagonists have demonstrated neuroprotection in focal and global cerebral ischemic models. We hypothesized that retrograde spinal cord venous perfusion with phenytoin, a NVSC antagonist, provides protection during prolonged spinal cord ischemia.
MATERIAL AND METHODS
In a rabbit model, spinal cord ischemia was induced for 45 minutes. Five groups of animals were studied. Controls, (Group I, n=8) received no intervention during aortic crossclamping. Group II (n=8) received systemic phenytoin (100 mg). Group III (n=8) received retrograde infusion of saline only. Groups IV (n=8) and V (n=9) received retrograde infusion of 50 mg and 100 mg of phenytoin, respectively (infusion rate: 0.8cc/kg/min during ischemic period). Mean arterial blood pressure (MAP) was monitored continuously. Animals were recovered for 24 hours before assessment of neurologic function using the Tarlov scale.
RESULTS
Tarlov scores (0=complete paraplegia, 1=slight lower limb movement, 2=sits with assistance, 3=sits alone, 4=weak hop, 5=normal hop) were as follows (mean
± SEM): Group I: 0.50± 0.50; Group II: 0.25± 0.46; Group III: 1.63± 0.56; Group IV: 4.13± 0.23; Group V: 4.22± 0.22. P<0.0001 IV, V vs I,II,III by ANOVA. No differences in MAP were observed.CONCLUSION
Spinal cord retrograde venous perfusion of phenytoin provides significant protection during periods of prolonged spinal cord ischemia.
