Oz Oyar Eser, Korkmaz Ayhan, Kardesş Ozgür, Omeroğlu Suna
Department of Physiology, Faculty of Medicine, Gazi University, Ankara, Turkey.
J Surg Res. 2008 Jun 1;147(1):143-7. doi: 10.1016/j.jss.2007.06.025. Epub 2007 Jul 30.
Spinal cord injury remains a devastating complication of thoracic and thoracoabdominal aortic operations. We aim to investigate the neuro-protective role of adrenomedullin (AM) administered to rabbits before ischemia and during reperfusion against ischemia-reperfusion (I/R) injury.
Occlusion of the abdominal aorta was applied to adult rabbits, followed by removal of aortic clamp and reperfusion. The abdominal aortas of New Zealand white albino rabbits were occluded for 30 min. Experimental groups were as follows: control group (sham operation group, n = 10), I/R group (n = 9) undergoing occlusion but receiving no pharmacologic intervention, AM-treated group (n = 8) receiving 0.05 microg/kg/min AM intravenously 10 min before ischemia and during reperfusion. Neurological status was assessed at 6, 24, and 48 h after the operation. All animals were killed at 48 h after the operation. Spinal cords were harvested for histopathologic and biochemical analyses.
According to Tarlov's scale, neurological status of the rabbits at postoperative hour 48 was better in the AM-treated group compared to the I/R group (P < 0.05). Decreased tissue and serum malondialdehyde levels and increased tissue and serum glutathione levels were observed in the AM-treated group (P < 0.05). In the same group tissue and serum nitrate levels were decreased (P < 0.05). Histopathologic analyses demonstrated typical morphological changes characteristic of necrosis in the I/R group. AM attenuated ischemia-induced necrosis.
To our knowledge, this is the first study that shows the effects of AM administered both preischemic and during reperfusion on induced oxidative damage to injured spinal cords. AM administration may significantly reduce the incidence of spinal cord injury following temporary aortic occlusion.
脊髓损伤仍然是胸主动脉和胸腹主动脉手术的一种严重并发症。我们旨在研究在缺血前及再灌注期间给予兔子肾上腺髓质素(AM)对缺血再灌注(I/R)损伤的神经保护作用。
对成年兔子实施腹主动脉阻断,随后移除主动脉夹并进行再灌注。将新西兰白兔的腹主动脉阻断30分钟。实验组如下:对照组(假手术组,n = 10),I/R组(n = 9),该组接受阻断但未接受药物干预,AM治疗组(n = 8),在缺血前10分钟及再灌注期间静脉注射0.05微克/千克/分钟的AM。在术后6、24和48小时评估神经状态。所有动物在术后48小时处死。采集脊髓进行组织病理学和生化分析。
根据塔尔洛夫量表,术后48小时,AM治疗组兔子的神经状态优于I/R组(P < 0.05)。AM治疗组的组织和血清丙二醛水平降低,组织和血清谷胱甘肽水平升高(P < 0.05)。在同一组中,组织和血清硝酸盐水平降低(P < 0.05)。组织病理学分析显示I/R组有典型的坏死形态学改变。AM减轻了缺血诱导的坏死。
据我们所知,这是第一项显示缺血前及再灌注期间给予AM对脊髓损伤诱导的氧化损伤影响的研究。给予AM可能显著降低临时主动脉阻断后脊髓损伤的发生率。