Dose dependent neuroprotection of the noble gas argon after cardiac arrest in rats is not mediated by KATP-Channel opening
Dose dependent neuroprotection of the noble gas argon after cardiac arrest in rats is not mediated by KATP-Channel opening
复制标题
DOI：
10.1016/j.resuscitation.2014.02.014
复制
发表时间：
2014-06-01
期刊：
影响因子：
6.5
通讯作者：
Fries, Michael
中科院分区：
文献类型：
--
作者：
Bruecken, Anne;Kurnaz, Pinar;Fries, Michael
目的：在大鼠心脏停搏（CA）后1h给予70%氩气具有神经保护作用。在啮齿动物模型中，我们研究了氩的神经保护作用是否是剂量依赖性的，并通过三磷酸腺苷依赖性钾（K-ATP）通道介导的。方法：47只雄性Sprague-Dawley大鼠进行7分钟的CA和3分钟的心肺复苏（CPR）。在方案I中，动物在成功CPR后1小时随机接受70%或40%氩气通气或不接受氩气治疗。第二个方案的动物也接受了1小时的70%氩气通气或无氩气治疗，但随机分配到接受KATP通道阻断剂5-羟基癸酸酯（5-HD）的组。对于所有动物的神经功能缺损评分（NDS），每天计算7天后，实验前的动物被杀死和脑收获的组织病理学分析。对照组动物在所有时间点均表现出重度神经功能障碍，如NDS所测量。氩处理的动物在所有术后天数内的NDS均显示出显著改善，且呈剂量依赖性。新皮层和海马CA 3/4区神经元损伤指数显著降低证实了这一点。管理5-HD既没有取消的积极影响，对功能恢复，也没有对组织病理学变化观察在argon group.Conclusion：我们的研究表明，在这个啮齿动物模型，这不是通过ATP依赖性钾通道介导的剂量依赖性的神经保护作用的氩管理。(C)2014爱思唯尔爱尔兰有限公司版权所有。
Purpose: Argon at a dosage of 70% is neuroprotective when given 1 h after cardiac arrest (CA) in rats. In a rodent model, we investigated if the neuroprotective effects of argon are dose dependent and mediated by adenosine triphosphate dependent potassium (K-ATP) channels.Methods: Forty-seven male Sprague-Dawley rats were subjected to 7 min of CA and 3 min of cardiopulmonary resuscitation (CPR). In protocol I animals were randomized to receive either 70% or 40% argon ventilation 1 h after successful CPR or no argon-treatment. Animals of the second protocol also received 1 h of 70% argon ventilation or no argon treatment but were randomized to a group receiving the KATP channel blocker 5-hydroxydecanoate (5-HD). For all animals a neurological deficit score (NDS) was calculated daily for seven days following the experiment before the animals were killed and the brains harvested for histopathological analyses.Results: All animals survived. Control animals exhibited severe neurologic dysfunction at all points in time as measured with the NDS. Argon treated animals showed significant improvements in the NDS through all postoperative days in a dose dependent fashion. This was paralleled by a significant reduction in the neuronal damage index in the neocortex and the hippocampal CA 3/4 region. Administration of 5-HD neither abolished the positive effects on functional recovery nor on histopathologic changes observed in the argon group.Conclusion: Our study demonstrates a dose dependent neuroprotective effect of argon administration in this rodent model, which is not mediated via ATP dependent potassium channels. (C) 2014 Elsevier Ireland Ltd. All rights reserved.