Retrograde perfusion with a sodium channel antagonist provides ischemic spinal cord protection.
BACKGROUND
Neuronal voltage-dependent sodium channel antagonists have been shown to provide neuroprotection in focal and global cerebral ischemic models. We hypothesized that retrograde spinal cord venous perfusion with phenytoin, a neuronal voltage-dependent sodium channel antagonist, would provide protection during prolonged spinal cord ischemia.


METHODS
In a rabbit model, spinal cord ischemia was induced for 45 minutes. Six groups of animals were studied. Controls (group I, n = 8) received no intervention during aortic cross-clamping. Group II (n = 8) received systemic phenytoin (100 mg). Group III (n = 4) received systemic phenytoin (200 mg). Group IV (n = 8) received retrograde infusion of room temperature saline (22 degrees C) only. Group V (n = 8) and group VI (n = 9) received retrograde infusion of 50 mg and 100 mg of phenytoin, respectively, (infusion rate: 0.8 mL x kg(-1) x min(-1) during the ischemic period). Mean arterial blood pressure was monitored continuously. Animals were allowed to recover 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 IV, 1.63 +/- 0.56; group V, 4.13 +/- 0.23; and group VI, 4.22 +/- 0.22 (p < 0.0001 V, VI versus I, II, IV by analysis of variance). No differences in mean arterial blood pressure were observed. All animals in group III became profoundly hypotensive and died before the conclusion of the 45-minute ischemic time.


CONCLUSIONS
Retrograde venous perfusion of the spinal cord with phenytoin, a voltage-sensitive sodium channel blocker, is safe and provides significant protection during prolonged spinal cord ischemia.
Gangemi
J J
JJ
Department of Surgery, University of Virginia Health Sciences Center, Charlottesville 22908, USA.
Kern
J A
JA
Ross
S D
SD
Shockey
K S
KS
Kron
I L
IL
Tribble
C G
CG
D000818:Animals; D001014:Aortic Aneurysm / Q000503:physiopathology / Q000601:surgery*; D004305:Dose-Response Relationship, Drug; D005260:Female; D007511:Ischemia / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D009460:Neurologic Examination / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010477:Perfusion; D010672:Phenytoin / Q000494:pharmacology*; D011817:Rabbits; D026941:Sodium Channel Blockers; D015222:Sodium Channels / Q000502:physiology; D013116:Spinal Cord / Q000098:blood supply*
D018696:Neuroprotective Agents; D026941:Sodium Channel Blockers; D015222:Sodium Channels; D010672:Phenytoin