Peri-ischemic aminoguanidine fails to ameliorate neurologic and histopathologic outcome after transient spinal cord ischemia.

Inhibition of neurotoxic events that lead to delayed cellular damage may prevent motor function loss after transient spinal cord ischemia. An important effect of the neuroprotective substance aminoguanidine (AG) is the inhibition of inducible nitric oxide synthase (iNOS), a perpetrator of focal ischemic damage. The authors studied the protective effects of AG on hind limb motor function and histopathologic outcome in an experimental model for spinal cord ischemia, and related these findings to the protein content of iNOS in the spinal cord. Temporary spinal cord ischemia was induced by 28 minutes of infrarenal balloon occlusion of the aorta in 40 anesthetized New Zealand White rabbits. Animals were assigned randomly to two treatments: saline (n = 20) or AG (n = 20: 100 mg/kg intravenously before occlusion). Postoperatively, treatment was continued with subcutaneous injections twice daily (saline or 100 mg/kg AG). Normothermia (38 degreesC) was maintained during ischemia, and rectal temperature was assessed before and after subcutaneous injections. Animals were observed for 96 hours for neurologic evaluation (Tarlov score), and the lumbosacral spinal cord was examined for ischemic damage after perfusion and fixation. Lastly, iNOS protein content was determined using Western blot analysis 48 hours after ischemia in five animals from each group. Neurologic outcome at 96 hours after reperfusion was the same in both groups. The incidence of paraplegia was 67% in the saline-treated group versus 53% in the AG-treated group. No differences in infarction volume, total number of viable motoneurons, or total number of eosinophilic neurons were present between the groups. At 48 hours after reperfusion, iNOS protein content in the spinal cord was increased in one animal in the AG-treated group and in three animals in the control group. The data indicate that peri-ischemic treatment with high-dose AG in rabbits offers no protection against a period of normothermic spinal cord ischemia. There was no conclusive evidence of spinal cord iNOS inhibition after treatment with AG