Systemic adenosine A2A agonist ameliorates ischemic reperfusion injury in the rabbit spinal cord
Systemic adenosine A2A agonist ameliorates ischemic reperfusion injury in the rabbit spinal cord
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DOI：
10.1016/s0003-4975(01)03057-0
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发表时间：
2001-10-01
影响因子：
4.6
通讯作者：
Kern, JA
中科院分区：
文献类型：
--
作者：
Cassada, DC;Gangemi, JJ;Kern, JA
背景腺苷A（2A）激动剂ATL-146 e（4-{3-[6-氨基-9-（5-乙基氨基甲酰基-3，4-二羟基-四氢-呋喃-2-基）-9H-嘌呤-2-基]-丙-2-炔基}-环己烷羧酸甲酯）已显示通过抑制活化的白细胞-内皮相互作用来预防多器官系统中的再灌注损伤。我们假设全身性ATL-146 e可以减少主动脉阻断后脊髓再灌注损伤。26只家兔接受了45分钟的肾下主动脉交叉夹闭。一组在再灌注期间静脉注射ATL-146 e 3小时。第二组仅接受媒介物并作为对照。使用Tarlov（0 - 5）评分系统在24和48小时评估动物的后肢功能。为了评估神经元的磨损，使用抗神经元损伤的抗SMI 33抗体对腰髓切片进行免疫染色。全身性ATL-146 e耐受，无血流动力学不稳定性。接受ATL-146 e的动物在脊髓缺血后24和48小时具有显著改善的神经学结果（p < 0.001）。与对照动物相比，接受ATL-146 e的动物的脊髓切片的前角中的神经元结构得到保留。在再灌注期间给予的静脉内ATL-146 e是耐受的，没有血液动力学不稳定性，并且导致缺血后脊髓功能的显著改善。通过保存腹角神经元。(C)2001年由胸外科医师协会出版。
Background. The adenosine A(2A) agonist ATL-146e (4-{3-[6-Amino-9-(5-ethylcarbamoyl-3,4-dihydroxy-tetrahydro-furan-2-yl)-9H-purin-2-yl]-prop-2-ynyl}- cyclohexanecarboxylic acid methyl ester) has been shown to prevent reperfusion injury in multiple organ systems through inhibition of activated leukocyte-endothelial interaction. We hypothesized that systemic ATL-146e could reduce spinal cord reperfusion injury after aortic clamping.Methods. Twenty-six rabbits underwent crossclamping of the infrarenal aorta for 45 minutes. One group received intravenous ATL-146e for 3 hours during reperfusion. A second cohort received only vehicle and served as controls. Animals were assessed at 24 and 48 hours using the Tarlov (0 to 5) scoring system for hind limb function. To evaluate neuronal attrition, immunostaining of lumbar spinal cord sections was performed using anti-SMI 33 antibody against neurofilament.Results. Systemic ATL-146e was tolerated without hemodynamic lability. Animals that received ATL-146e had significantly improved neurologic outcomes 24 and 48 hours after spinal cord ischemia (p < 0.001). There was preservation of neuronal architecture in the ventral horn of spinal cord sections from animals receiving ATL-146e compared with control animals.Conclusions. Intravenous ATL-146e given during reperfusion is tolerated without hemodynamic lability, and results in substantially improved spinal cord function after ischemia. by preservation of ventral horn neurons. (C) 2001 by The Society of Thoracic Surgeons.