Sang Hanfei, Cao Lin, Qiu Pengxin, Xiong Lize, Wang Rongrong, Yan Guangmei
Department of Pharmacology, Zhongshan Medical College, Guangzhou, China.
Anesthesiology. 2006 Nov;105(5):953-60. doi: 10.1097/00000542-200611000-00016.
Whether isoflurane preconditioning produces delayed neuroprotection in the spinal cord is unclear. The authors tested the hypothesis that isoflurane produces delayed preconditioning against spinal cord ischemic injury and, further, that the beneficial effect is dependent on free radicals.
In experiment 1, 63 rabbits were randomly assigned to seven groups (n = 9 each): Animals in the control group only underwent spinal cord ischemia without pretreatment; animals in the Iso24h, Iso48h, and Iso72h groups received 40 min of 1.0 minimum alveolar concentration isoflurane in 100% oxygen each day for 5 consecutive days, with the last pretreatment at 24, 48, and 72 h, respectively, before spinal cord ischemia; animals in the O2 24h, O2 48h, and O2 72h groups received 40 min of 100% oxygen each day for 5 consecutive days, with the last pretreatment at 24, 48, and 72 h, respectively, before spinal cord ischemia. In experiment 2, 48 rabbits were randomly assigned into four groups (n = 12 each): Animals in the O2 and Iso groups received 3 ml/kg saline intraperitoneally 1 h before each session of oxygen pretreatment and isoflurane pretreatment, respectively. In the DMTU+Iso and DMTU+O2 groups, 10% dimethylthiourea (DMTU, a potent free radical scavenger) dissolved in saline (3 ml/kg) was administered at the same time point. Twenty-four hours after the last pretreatment, animals were subjected to spinal cord ischemia. Spinal cord ischemia was induced by an infrarenal aorta clamping for 20 min. Forty-eight hours after reperfusion, neurologic function and histopathology of the spinal cord were examined.
In experiment 1, the neurologic and histopathologic outcomes in the Iso24h and Iso48h groups were better than those in the control group (P < 0.005 for each comparison); the neurologic and histopathologic outcomes in the control group showed no significant differences in comparison with the O2 24h, O2 48h, O2 72h, and Iso72h groups (P > 0.05 for each comparison). In experiment 2, the neurologic and histopathologic outcomes in the Iso group were better than those in the DMTU+Iso, O2, and DMTU+O2 groups (P < 0.01 for each comparison); there were no significant differences in the neurologic and histopathologic outcomes among the DMTU+Iso, O2, and DMTU+O2 groups (P > 0.05 for each comparison).
Isoflurane produces delayed preconditioning against spinal cord ischemic injury, and the beneficial effect may be dependent on the release of free radicals.
异氟烷预处理是否能对脊髓产生延迟性神经保护作用尚不清楚。作者检验了以下假设：异氟烷可产生针对脊髓缺血性损伤的延迟预处理作用，并且，这种有益作用依赖于自由基。
在实验1中，63只兔子被随机分为7组（每组n = 9）：对照组动物仅经历脊髓缺血，未进行预处理；异氟烷24小时组、异氟烷48小时组和异氟烷72小时组的动物，连续5天每天接受40分钟1.0最低肺泡浓度的异氟烷与100%氧气混合气体，最后一次预处理分别在脊髓缺血前24、48和72小时进行；氧气24小时组、氧气48小时组和氧气72小时组的动物，连续5天每天接受40分钟100%氧气，最后一次预处理分别在脊髓缺血前24、48和72小时进行。在实验2中，48只兔子被随机分为4组（每组n = 12）：氧气组和异氟烷组的动物在每次氧气预处理和异氟烷预处理前1小时分别腹腔注射3 ml/kg生理盐水。在二甲基硫脲 + 异氟烷组和二甲基硫脲 + 氧气组，在相同时间点给予溶解于生理盐水（3 ml/kg）的10%二甲基硫脲（DMTU，一种有效的自由基清除剂）。最后一次预处理24小时后，动物接受脊髓缺血。通过夹闭肾下主动脉20分钟诱导脊髓缺血。再灌注48小时后，检查脊髓神经功能和组织病理学。
在实验1中，异氟烷24小时组和异氟烷48小时组的神经功能和组织病理学结果优于对照组（每次比较P < 0.005）；对照组与氧气24小时组、氧气48小时组、氧气72小时组和异氟烷72小时组相比，神经功能和组织病理学结果无显著差异（每次比较P > 0.05）。在实验2中，异氟烷组的神经功能和组织病理学结果优于二甲基硫脲 + 异氟烷组、氧气组和二甲基硫脲 + 氧气组（每次比较P < 0.01）；二甲基硫脲 + 异氟烷组、氧气组和二甲基硫脲 + 氧气组之间的神经功能和组织病理学结果无显著差异（每次比较P > 0.05）。
异氟烷可产生针对脊髓缺血性损伤的延迟预处理作用，且这种有益作用可能依赖于自由基的释放。
