Experimental studies of pathophysiology and treatment of spinal cord ischemia

背景和目的：截瘫是胸主动脉瘤手术后的严重并发症。脊髓缺血性损伤的病理生理学基础研究及防治具有重要意义。采用兔或大鼠脊髓缺血模型，研究脊髓缺血的病理生理学机制，并评价可能的神经保护措施。方法：阻断兔肾下主动脉或大鼠胸主动脉20分钟造成脊髓缺血。用彩色微球法测定缺血期兔脊髓血流量。监测节段性脊髓诱发电位(SSCEP)。用鞘内微透析探头测定大鼠脑脊液中兴奋性氨基酸的含量。在结果研究中，兔在氟烷或硫喷妥钠(脑电突发抑制)麻醉下进行常温缺血，或在低温(35ﾟC或…)下进行氟烷麻醉下32ﾟC)以上缺血。在另一组动物中，用L-NAME、苯肾上腺素或赋形剂预处理后，兔造成常温缺血。使用苯肾上腺素将平均动脉压提高到与L名字组相同的水平。结果：诱导脑缺血后，SSCEP在20分钟内消失，20~30分钟恢复到缺血前水平。再循环后10min，L4~L7脊髓可见中度充血。再循环60分钟和120分钟后均未检测到低灌注率。截瘫动物再循环6小时后脊髓血流量增加。脑脊液中谷氨酸浓度在缺血时升高2.5倍，再灌流1h后恢复到缺血前水平。在结果研究中，亚低温组(35ﾟC和32ﾟC)没有表现出神经功能缺陷，而硫喷妥组表现出与对照组相似的神经功能缺陷。与赋形剂对照组相比，注射L名字的兔表现出明显更好的神经学结果。结论：脊髓缺血后运动功能的下降既不是由于延迟性低灌流所致，也不是由于一氧化氮毒性所致，谷氨酸可能参与了脊髓缺血损伤。在缺血期略微降低体温可以提供显著的保护作用，而硫喷妥钠的剂量会产生最大的代谢抑制，但不能保护脊髓。较少

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