Comparison of systemic and retrograde delivery of adenosine A2A agonist for attenuation of spinal cord injury after thoracic aortic cross-clamping
Comparison of systemic and retrograde delivery of adenosine A2A agonist for attenuation of spinal cord injury after thoracic aortic cross-clamping
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DOI：
10.1016/j.athoracsur.2005.09.023
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发表时间：
2006-03-01
影响因子：
4.6
通讯作者：
Kern, JA
中科院分区：
文献类型：
--
作者：
Reece, TB;Okonkwo, DO;Kern, JA
背景。截瘫仍然是胸主动脉手术的致命并发症，逆行腺苷和全身性腺苷a （2A）受体激活可以减轻这种并发症。我们假设，尽管逆行脊髓灌注了腺苷A（2A）激动剂（ATL-146e），全身治疗仍能产生良好的脊髓保护作用，减少炎症。40头猪接受30分钟的胸主动脉交叉夹闭。实验组猪：未治疗（对照组）；逆行生理盐水（对照）；逆行atl - 146 e;系统性的atl - 146 e;全身ATL-146e与逆行生理盐水；或系统和逆行ATL-146e。缺血时给予逆行治疗。系统ATL-146e (0.06 μ g；公斤(1)。再灌注时静脉给予Min(-1) 3小时。24小时时，用Tarlov量表评估运动功能。分析组织的神经元活力、微管相关蛋白-2表达和中性粒细胞隔离（髓过氧化物酶活性）。4头猪接受逆行钡剂治疗，显示放射学和组织学上的脊髓灌注。除ATL-146e联合组外，ATL组24小时Tarlov评分均较对照组显著提高（p < 0.05）。全身ATL组与对照组相比，苏木精染色和伊红染色显示神经元活力明显保持（p < 0.05）。在所有系统性ATL组中，与对照组相比，微管相关蛋白-2的表达均显著保留。与对照组相比，全身性ATL显著降低髓过氧化物酶活性（p < 0.01）。逆行和全身性ATL-146e治疗均能减轻缺血性脊髓损伤，但两者联合治疗效果较差。考虑到两种途径的效果比较，以及全身输送的简单性，再灌注时外周静脉ATL-146e应优先用于胸主动脉手术脊髓保护。
Background. Paraplegia remains a devastating complication of thoracic aortic surgery, which has been attenuated by retrograde adenosine and systemic adenosine A(2A) receptor activation. We hypothesized that despite retrograde spinal perfusion of an adenosine A(2A) agonist (ATL-146e), systemic therapy produces superior spinal cord protection with reduced inflammation.Methods. Forty pigs underwent 30-minute thoracic aortic cross-clamping. Pigs received: no therapy (control); retrograde saline (retrograde control); retrograde ATL-146e; systemic ATL-146e; systemic ATL-146e with retrograde saline; or systemic and retrograde ATL-146e. Retrograde therapies were given during ischemia. Systemic ATL-146e (0.06 mu g . kg(-1) . min(-1)) was given intravenously for 3 hours at reperfusion. At 24 hours, motor function was assessed using the Tarlov scale. Tissue was analyzed for neuronal viability, microtubule-associated protein-2 expression, and neutrophil sequestration (myeloperoxidase activity).Results. Four pigs received retrograde barium showing both radiographic and histologic spinal cord perfusion. Tarlov scores at 24 hours were significantly improved versus both control groups in all ATL groups except the combined ATL-146e group (all p < 0.05). Neuronal viability by hematoxylin and eosin stain was significantly preserved in systemic ATL groups compared with both control groups (all p < 0.05). Microtubule-associated protein-2 expression was significantly preserved compared with both control groups in all systemic ATL groups. Systemic ATL significantly lowered myeloperoxidase activity versus both control groups (p < 0.01).Conclusions. Both retrograde and systemic ATL-146e therapies attenuate ischemic spinal cord injury, but combining the two routes was less effective. Given comparable results between the two routes and the simplicity of systemic delivery, peripheral venous ATL-146e at reperfusion should be preferred for spinal cord protection in thoracic aortic surgery.