Department of Cardiothoracic Surgery, University of Colorado, Denver, Colo 80045, USA.
J Thorac Cardiovasc Surg. 2011 Jan;141(1):256-60. doi: 10.1016/j.jtcvs.2010.09.017.
Paraplegia remains a devastating complication for patients undergoing thoracic aortic procedures. Although surgical adjuncts have evolved to reduce the risk of paraplegia, no pharmacologic therapies have proven efficacious in attenuating spinal cord ischemia-reperfusion injury. Effects of erythropoietin in spinal cord ischemia-reperfusion injury, however, have not yet been elucidated. We hypothesized that pretreatment with erythropoietin would attenuate functional and cytoarchitectural spinal cord injury related to high-risk aortic procedures.
Adult male mice were subjected to ischemia-reperfusion. Aortic arch and proximal left subclavian arteries were clamped for 5 minutes; animals were observed for 48 hours. Neurologic scores of hind limb function were assessed every 12 hours. Experimental groups consisted of treatment with erythropoietin 4 hours before crossclamping (n = 7), ischemic controls (n = 7), and sham ischemia (operation without crossclamping, n = 6). Thoracolumbar sections of spinal cord were removed after 48 hours and preserved for cytoarchitectural analysis.
Mice pretreated with erythropoietin exhibited significant preservation of hind limb motor function. All mice without pretreatment were paralyzed at 48 hours. Mice with erythropoietin pretreatment had improved motor function; 3 had no measurable neurologic deficit at 48 hours. Histologic analysis in mice treated with erythropoietin showed markedly reduced neuronal cell injury.
Erythropoeitin preserves both function and histologic appearance in mice undergoing spinal cord ischemia-reperfusion. With further elucidation of mechanisms of protection and optimal administration, erythropoietin could become an important adjunct in reducing the incidence and severity of spinal cord injury related to aortic interventions.
截瘫仍然是胸主动脉手术患者的一种毁灭性并发症。尽管外科辅助手段已经发展到降低截瘫的风险，但没有任何药物治疗方法已被证明能有效减轻脊髓缺血再灌注损伤。然而，促红细胞生成素对脊髓缺血再灌注损伤的影响尚未阐明。我们假设促红细胞生成素预处理会减轻与高危主动脉手术相关的脊髓功能和细胞结构损伤。
成年雄性小鼠接受缺血再灌注。夹闭主动脉弓和左锁骨下动脉近端 5 分钟；观察动物 48 小时。每隔 12 小时评估后肢功能的神经评分。实验组包括在夹闭前 4 小时用促红细胞生成素治疗（n = 7）、缺血对照（n = 7）和假手术（不夹闭，n = 6）。缺血再灌注 48 小时后取出胸腰椎脊髓切片并保存用于细胞结构分析。
用促红细胞生成素预处理的小鼠后肢运动功能明显保存。未经预处理的所有小鼠在 48 小时时均瘫痪。用促红细胞生成素预处理的小鼠运动功能改善；48 小时时有 3 只没有可测量的神经缺陷。用促红细胞生成素治疗的小鼠的组织学分析显示神经元细胞损伤明显减少。
促红细胞生成素可保存经历脊髓缺血再灌注的小鼠的功能和组织学外观。随着对保护机制和最佳给药方法的进一步阐明，促红细胞生成素可能成为降低与主动脉干预相关的脊髓损伤发生率和严重程度的重要辅助手段。
