Effects Of Retrograde Venous Perfusion With Hypothermic NMDA Antagonist MK-801for Protection Of The Spinal Cord Injury

Purpose:Spinal cord injury, caused by ischemia and reperfusion, is a devastating complication after aortic surgery, of which the mechanism and protective modalities are still on controversy. This study focuses on the mid-long term effects of retrograde venous perfusion with hypothermic NMDA antagonist for protection of the spinal cord injury, in order to develop a simple safe reliable spinal cord protection intervention.Methods:24adult healthy Tibet miniature swine was randomized into four groups:Group A (sham group, n=6), Group B (control group, n=6), Group C (hypothermic Ringer’s solution perfusion group, n=6) and group D (hypothermic MK-801solution perfusion group, n=6). The spinal cord injury was induced by clamping the descending aorta and left subclavian artery for70min. Animals in group C and D was infused with hypothermic Ringer’s solution and MK-801solution through the accessory hemiazygous vein during the ischemia and1h reperfusion phases. The proximal and distal blood pressures, nasopharyngeal temperature and heart rate were recorded every10min. SSEPs and blood gas analysis were done every10min and30min. Hind-leg motor activity was evaluated on6h,24h and30d after reperfusion in accordance to Tarlov standard. And the spinal cord sample of L3were harvested30d after reperfusion, followed by HE staining, nissl staining and MAP-2immunohistochemistry analysis. Results:The spinal cord injury model was established successfully. There was no paraplegia or paralysis in group A. The animals in group B had a mean Tarlov score of1.0±1.3,1.7±1.2and2.7±0.8on6h,24h and30d after reperfusion. The animals in group C had a mean Tarlov score of2.7±0.5,2.8±0.8and3.5±0.5on6h,24h and30d after reperfusion. The animals in group D had a mean Tarlov score of3.2±0.8,3.3±0.5and3.8±0.4on6h,24h and30d after reperfusion. And there were significant difference among these four groups. The motor neuron count of group D (21±1.7) was more than that of group B (15±2.3) and group C (18±2.4). However, there was significant difference between group A (24±1.5) and group D (21±1.7) in motor neuron count. The immunohistochemistry indicated that the expression of MAP-2was decreased in group B and group C. And the latency of SSEPs was prolonged while the amplitude was decreased in group B, groupC and group D during the ischemia phase.Conclusion:clamping the descending aorta and left subclavian artery for70min can establish a kind of reliable spinal cord injury model. Retrograde Venous Perfusion with Hypothermic NMDA Antagonist MK-801via the accessory hemiazygous vein has certain protective effect for spinal cord injury, however this effect was limited.