Ethyl pyruvate improves survival in awake hemorrhage.
Ethyl pyruvate improves survival in awake hemorrhage.
复制标题
DOI：
10.1007/s00109-009-0441-8
复制
发表时间：
2009-04
影响因子：
4.7
通讯作者：
Ulloa, Luis
中科院分区：
文献类型：
--
作者：
Cai, Bolin;Brunner, Michael;Wang, Haichao;Wang, Ping;Deitch, Edwin A.;Ulloa, Luis
经典的出血实验模型的特点是使用麻醉剂，这可能会干扰出血/复苏的典型免疫反应和病理。因此，在麻醉动物中成功的治疗策略在临床试验中可能并不有益。在这项研究中，我们分析了丙酮酸乙酯是否可以在清醒（非麻醉）出血的复苏过程中提供治疗益处。我们的研究结果表明，为达到相同的目标平均动脉血压，未麻醉动物出血所需的取血量比麻醉动物高约25%。醒鼠复苏时用Hextend恢复循环容量，提高生存率。然而，75%以上用Hextend复苏的动物在出血后的第一个小时内死亡。用含有50mm丙酮酸乙酯的Hextend进行复苏，保护了87%以上的动物。这种生存益处与代谢标志物的显著变化无关，但与复苏期间的抗炎潜力有关。与麻醉动物的经典出血不同，丙酮酸乙酯在未麻醉的啮齿动物中明显早于Hextend重建平均动脉血压。在相同血压下，未麻醉动物血清肿瘤坏死因子(TNF)-α比麻醉动物高2倍。这一过程不是由于单一器官的反应，而是影响到所有被分析的器官，包括肺、心、脾和肝。虽然用Hextend复苏不能降低全身TNF-α水平，但它能抑制肺、心脏和肝脏的TNF-α水平，而对脾脏无抑制作用。与Hextend不同，丙酮酸乙酯复苏可防止血清TNF-α水平升高，并减弱包括脾脏在内的所有器官的TNF-α反应。这些研究表明，麻醉动物的炎症反应与未麻醉动物不同，清醒出血可以为复苏期间抗炎策略的研究提供优势。丙酮酸乙酯可以减轻复苏期间的全身炎症反应，提高清醒出血实验模型的存活率。
Classical experimental models of hemorrhage are characterized by the use of anesthetics that may interfere with the typical immune responses and pathology of hemorrhage/resuscitation. Thus, therapeutic strategies successful in anesthetized animals might not be beneficial in clinical trials. In this study, we analyzed whether ethyl pyruvate could provide therapeutic benefits during resuscitation in awake (unanesthetized) hemorrhage. Our results indicate that hemorrhage in unanesthetized animals required approximately 25% higher blood withdrawal than anesthetized animals to achieve the same targeted mean arterial blood pressure. Resuscitation with Hextend reestablished circulatory volume and improved survival during resuscitation of awake rodents. Yet, over 75% of the animals resuscitated with Hextend died within the first hours after hemorrhage. Resuscitation with Hextend containing 50 mM ethyl pyruvate protected over 87% of the animals. This survival benefit did not correlate with significant changes in the metabolic markers but with an anti-inflammatory potential during resuscitation. Unlike classical hemorrhage in anesthetized animals, ethyl pyruvate reestablished mean arterial blood pressure significantly earlier than Hextend in unanesthetized rodents. Unanesthetized animals showed twofold higher serum tumor necrosis factor (TNF)-α than anesthetized animals subjected to the same blood pressure. This process was not due to the response of a single organ, but affected all the analyzed organs including the lung, heart, spleen, and liver. Although resuscitation with Hextend failed to attenuate systemic TNF-α levels, it inhibited TNF-α levels in the lung, heart, and liver but not in the spleen. Unlike Hextend, resuscitation with ethyl pyruvate prevented high serum TNF-α levels and blunted TNF-α responses in all the organs including the spleen. These studies indicate that the inflammatory responses in anesthetized animals differ from that in unanesthetized animals and that awake hemorrhage can provide advantages in the study of anti-inflammatory strategies during resuscitation. Ethyl pyruvate may attenuate systemic inflammatory responses during resuscitation and improve survival in experimental models of awake hemorrhage.
登录
查看更多内容
NF-kappab家族成员Rela的需求在次级淋巴机构的发展中。
DOI：
10.1084/jem.20011885
发表时间：
2002-01-21
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Alcamo E;Hacohen N;Schulte LC;Rennert PD;Hynes RO;Baltimore D
通讯作者：
Baltimore D
DOI：
10.1124/jpet.104.079707
发表时间：
2005-03-01
影响因子：
3.5
作者：
Han, YS;Englert, JA;Fink, MP
通讯作者：
Fink, MP
影响因子：
2.7
作者：
Malik, AA;Radhakrishnan, N;Singhal, PC
通讯作者：
Singhal, PC
影响因子：
3.1
作者：
Handrigan, MT;Bentley, TB;Atkins, JL
通讯作者：
Atkins, JL
影响因子：
56.9
作者：
Li, QT;Van Antwerp, D;Verma, IM
通讯作者：
Verma, IM