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。有关脊髓缺血性损伤的病理生理学和保护的基础研究是非常重要的。采用兔或大鼠脊髓缺血模型，我们研究了脊髓缺血的病理生理学和评估潜在的保护措施，对神经damage.Methods：脊髓缺血造成阻塞肾下主动脉在兔或阻塞胸主动脉在大鼠20分钟。采用彩色微球法测定兔脊髓缺血前后的血流量。监测节段性脊髓诱发电位（SSCEP）。使用鞘内微透析探针测量大鼠CSF中的兴奋性氨基酸。在结果研究中，家兔在氟烷或硫喷妥钠（EEG爆发抑制）麻醉下进行常温缺血，或在低温（35 ℃或35 ℃）下进行缺血。 关于我们 32 ℃）氟烷麻醉下局部缺血。在另一个系列中，家兔在用L-NAME、苯丙氨酸甲酯或溶剂预处理后进行常温缺血。给予苯丙氨酸氨基转移酶以使平均动脉血压升高至与L-NAME组相同的水平。结果：诱导缺血后20 min内，SSCEP消失，20-30 min恢复到缺血前状态。再循环后10分钟，在L4-L7脊髓中观察到中度充血。再循环60和120分钟后未检测到灌注不足。截瘫动物再循环6小时后脊髓血流量增加。脑脊液中谷氨酸浓度在缺血期间增加2.5倍，并在1小时再循环后恢复到缺血前水平。在结果研究中，低温组（35 ℃和32 ℃）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。与溶剂对照组相比，L-NAME预处理的家兔表现出明显更好的神经功能结局。结论：这些结果表明，脊髓缺血后运动功能的恶化既不是由于延迟性低灌注，也不是一氧化氮毒性，谷氨酸可能在缺血性损伤中发挥作用。在缺血期体温的轻微下降提供了显著的保护，而硫喷妥钠，在产生最大代谢抑制的剂量，不保护脊髓。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