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Background: This study was conducted to investigate the effect of memantine, a noncompetitive N-methyl-d-aspartate receptor antagonist, on the neurologic outcome of spinal cord ischemia after aortic occlusion. Materials and methods: New Zealand White rabbits were anesthetized and spinal cord ischemia was induced for 40 minutes by infrarenal aortic occlusion. Animals were randomly allocated to 3 groups. Group 1 (n = 8, control) received no pharmacologic intervention, group 2 (n = 8) received intra-aortic memantine infusion (20 mg/kg) after aortic crossclamping, and group 3 (n = 8) was treated with systemic memantine infusion (20 mg/kg) 45 minutes before aortic occlusion. Neurologic status was scored by the Tarlov system (in which 4 is normal and 0 is paraplegia) at 12, 24, 36, and 48 hours after the operation. Lumbar spinal root stimulation potentials and motor evoked potentials from lower limb muscles were monitored before, during, and after the operation. After the animals were killed, the spinal cords were studied histopathologically. Results: All potentials disappeared shortly after aortic crossclamping. They returned earlier in both memantine-treated groups than in the placebo group. Histologic examination of spinal cords revealed a few abnormal motor neurons in memantine-treated rabbits but found extensive injury in the control group. At 12 hours the median Tarlov scores were 0 in the control group (group 1), 2 in the intra-aortic memantine group (group 2, P = .001 versus control), and 3 in the systemic group (group 3, P = .0002 versus control). At 24 hours median Tarlov scores were 0, 2.5 (P = .0002), and 4 (P = .0002), respectively. Finally, at both 36 and 48 hours median Tarlov scores were 0, 3 (P = .0006), and 4 (P = .0002), respectively. Conclusion: Memantine significantly reduced neurologic injury related to spinal cord ischemia and reperfusion after aortic occlusion. (J Thorac Cardiovasc Surg 1999;117:285-91)