Experimental studies of pathophysiology and treatment of spinal cord ischemia

背景与目的：截瘫是胸主动脉瘤术后的严重并发症。脊髓缺血性损伤的病理生理及保护的基础研究具有重要意义。采用家兔或大鼠脊髓缺血模型，研究脊髓缺血的病理生理机制，探讨脊髓缺血对神经系统损伤的潜在保护措施。方法：阻断家兔肾下主动脉或阻断大鼠胸主动脉使脊髓缺血20分钟。用彩色微球法测定兔缺血前后脊髓血流。监测脊髓节段性诱发电位（SSCEP）。用鞘内微透析探针测定大鼠脑脊液中的兴奋性氨基酸。结果研究中，兔分别在氟烷或硫喷妥钠（脑电图抑制爆发）麻醉下进行常温缺血，或在氟烷麻醉下进行低温（35或32以上）缺血。在另一个系列中，家兔在L-NAME、苯肾上腺素或载药预处理后遭受常温缺血。给予苯肾上腺素使平均动脉血压升高到与L-NAME组相同的水平。兔在缺血后48小时恢复并进行神经分级。结果：缺血诱导后，SSCEP在20分钟内消失，20 ~ 30分钟恢复到缺血前模式。再循环后10分钟，L4-L7脊髓出现中度充血。再循环60和120分钟后未发现灌注不足。截瘫动物再循环6小时后脊髓血流量增加。脑脊液谷氨酸浓度在缺血时增加2.5倍，再循环1小时后恢复到缺血前水平。在结果研究中，低温组（35 C和32 C）没有表现出神经功能缺损，而硫喷妥钠组表现出与对照组相似的神经功能缺损。与对照组相比，经L-NAME预处理的家兔神经功能明显改善。经苯肾上腺素预处理的家兔未出现神经功能缺损。结论：脊髓缺血后运动功能的恶化既不是迟发性低灌注所致，也不是一氧化氮毒性所致，谷氨酸可能在缺血损伤中起一定作用。缺血前后体温的轻微下降提供了显著的保护，而硫喷妥钠的剂量可产生最大的代谢抑制，但不能保护脊髓。少

Background and Purpose : Paraplegia is a serious complication after surgery of thoracic aortic aneurysm. Basic studies concerning pathophysiology of and protection against ischemic damage of the spinal cord are of great importance. Using a rabbit or rat model of spinal cord ischemia, we investigated the pathophysiology of the spinal cord ischemia and evaluated the potential protective measures against the neurologic damage.Methods : Spinal cord ischemia was produced by occluding infrarenal aorta in rabbits or by occluding thoracic aorta in rats for 20 minutes. Spinal cord blood flow in rabbits was measured by colored microsphere method in a peri-ischemic period. Segmental spinal cord evoked potential (SSCEP) was monitored. Excitatory amino acids in CSF of the rat were measured using an intrathecal microdialysis probe. In the outcome study, rabbits were subjected to either normothermic ischemia under halothane or thiopental (burst-suppression on EEG) anesthesia, or hypothermic (35ﾟC or … More 32ﾟC) ischemia under halothane anesthesia. In another series, rabbits were subjected to normothermic ischemia after pretreatment with L-NAME,phenylephrine, or vehicle. Phenylephrine was administered to increase mean arterial blood pressure to the same level as the L-NAME group. Rabbits were allowed to recover and were graded neurologically at 48 hours after ischemia.Results : After induction of ischemia, SSCEP disappeared within 20 minutes and returned back to preischemic pattern in 20-30 minutes. At 10 minutes after recirculation, moderate hyperemia was observed in L4-L7 spinal cord. No hypoperfusion was detected after 60 and 120 minutes of recirculation. Spinal cord blood flow increased after 6 hours of recirculation in paraplegic animals. The glutamate concentration in the CSF increased 2.5 fold during ischemia and returned to the preischemic level after 1 hour recirculation. In the outcome studies, the hypothermia groups (both 35ﾟC and 32ﾟC) exhibited no neurologic deficit while the thiopental group exhibited neurologic deficit similar to that of the control group. Rabbits pretereated with L-NAME showed significantly better neurologic outcome compared with vehicle controls. Rabbits pretreated with phenylephrine exhibited no neurologic deficit.Conclusions : These results show that deterioration of motor function after spinal cord ischemia is neither due to delayd hypoperfusion nor nitric oxide toxicity and that glutamate may play a role in the ischemic injury. A slight decrease in body temperature in the peri-ischemic period provides significant protection, while thiopental, in a dose to produce maximal metabolic depression, does not protect the spinal cord. Less