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 mod els. We hypothesized that retrograde spinal cord venous perfusion with phen ytoin, a neuronal voltage-dependent sodium channel antagonist, would provid e 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 syste mic phenytoin (100 mg). Group III (n = 4) received systemic phenytoin (200 mg). Group IV (n = 8) received retrograde infusion of room temperature sali ne (22 degrees C) only. Group V (n = 8) and group VI (n = 9) received retro grade infusion of 50 mg and 100 mg of phenytoin, respectively, (infusion ra te: 0.8 mL . kg(-1) . min(-1) during the ischemic period). Mean arterial bl ood pressure was monitored continuously. Animals were allowed to recover fo r 24 hours before assessment of neurologic function using the Tarlov scale. Results. Tarlov scores (0 = complete paraplegia, 1 slight lower limb moveme nt, 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 N, 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 dif ferences in mean arterial blood pressure were observed. All animals in grou p III became profoundly hypotensive and died before the conclusion of the 4 5-minute ischemic time. Conclusions. Retrograde venous perfusion of the spinal cord with phenytoin, a voltage-sensitive sodium channel blocker, is safe and provides significa nt protection during prolonged spinal cord ischemia. (C) 2000 by The Societ y of Thoracic Surgeons.