Intensive Care Unit, Delafontaine Hospital, Saint Denis, France.
Shock. 2010 Apr;33(4):353-62. doi: 10.1097/SHK.0b013e3181b65b99.
The present study evaluates the role of the inflammatory status and apoptosis activation in the development of organ dysfunction after brain death using plasma assays and macroarray analysis on skeletal muscle biopsies to look for evidence of remote tissue damage in two intensive care units in France and one in Belgium. As controls, we used patients undergoing hip surgery and healthy volunteers. Causes of brain death in the 85 consecutive patients included in the study were cardiac arrest (n = 29; 34%), stroke (n = 42; 49%, with 38 patients having hemorrhagic stroke), and head injury (n = 14; 17%). Of the 85 patients, 45 donated 117 organs. Plasma endotoxin and cytokine levels indicated a marked systemic inflammatory response in brain-dead patients, which was strongest in the cardiac arrest group. Leukocyte dysfunction, as assessed by cytokines production in response to various stimuli, was noted in a subgroup of patients with brain death after stroke. Interestingly, skeletal muscle biopsies showed no increase in mRNAs for genes related to inflammation, whereas mRNAs for both antiapoptotic and proapoptotic genes were increased, the balance being in favor of apoptosis induction. The increased activation of the proapoptotic caspase 9 was further confirmed by Western blot. In conclusion, the presence of inflammation and apoptosis induction may explain the rapid organ dysfunction seen after brain death. Both abnormalities may play a role in organ dysfunction associated with brain death. However, the level of systemic inflammation or the presence of circulating endotoxin was not associated with lower graft survival.
本研究通过对法国两个重症监护病房和比利时一个重症监护病房的骨骼肌活检进行血浆检测和宏阵列分析，评估了炎症状态和细胞凋亡激活在脑死亡后器官功能障碍发展中的作用，以寻找远程组织损伤的证据。作为对照，我们使用接受髋关节手术的患者和健康志愿者。纳入研究的 85 例连续脑死亡患者的病因包括心脏骤停（n=29；34%）、中风（n=42；49%，其中 38 例为出血性中风）和头部损伤（n=14；17%）。85 例患者中有 45 例捐献了 117 个器官。血浆内毒素和细胞因子水平表明脑死亡患者存在明显的全身炎症反应，其中以心脏骤停组最为强烈。在中风后发生脑死亡的患者亚组中，白细胞功能障碍（通过对各种刺激产生细胞因子的能力评估）。有趣的是，骨骼肌活检显示与炎症相关的基因的 mRNA 没有增加，而抗凋亡和促凋亡基因的 mRNA 均增加，凋亡诱导的平衡占优势。促凋亡 caspase-9 的增加激活进一步通过 Western blot 得到证实。总之，炎症的存在和细胞凋亡的诱导可能解释了脑死亡后迅速发生的器官功能障碍。这两种异常可能在与脑死亡相关的器官功能障碍中起作用。然而，全身性炎症水平或循环内毒素的存在与移植物存活率降低无关。
