A biomimetic membrane device that modulates the excessive inflammatory response to sepsis.
A biomimetic membrane device that modulates the excessive inflammatory response to sepsis.
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DOI：
10.1371/journal.pone.0018584
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发表时间：
2011-04-14
期刊：
影响因子：
3.7
通讯作者：
Humes HD
中科院分区：
文献类型：
--
作者：
Ding F;Song JH;Jung JY;Lou L;Wang M;Charles L;Westover A;Smith PL;Pino CJ;Buffington DA;Humes HD
感染性休克的临床死亡率接近50%。脓毒症的主要临床表现是由于宿主对感染的反应失调，而不是入侵病原体的直接后果。这种初始免疫应答的中心是白细胞和微血管内皮的活化，导致心血管不稳定、肺损伤和肾功能障碍。由于白细胞活化在脓毒症综合征中的主要作用，开发了一种称为选择性细胞增殖装置（SCD）的合成仿生膜来结合活化的白细胞。将SCD沿着体外血液回路结合，并使用柠檬酸盐进行局部抗凝以降低血液离子钙，旨在调节脓毒症中的白细胞活化。实验室调查。密歇根大学医学院。体重30-35公斤的猪。为了评估SCD在感染性休克中的作用，将30×1010个细菌/kg体重的大肠埃希菌注入猪的腹腔，并在1小时内立即置于含有SCD的体外回路中。在该动物模型中，与未使用SCD或使用肝素抗凝的对照组相比，使用柠檬酸盐的SCD改善了心血管不稳定性和活化白细胞的肺隔离，减少了肾功能不全，并与各种对照组相比延长了生存时间。该效应与全身循环中性粒细胞活化的最小升高相关。这些临床前研究沿着两项有利的探索性临床试验构成了FDA批准的研究器械豁免的基础，该豁免适用于目前正在进行的关键性多中心随机对照试验。
Septic shock has a clinical mortality rate approaching fifty percent. The major clinical manifestations of sepsis are due to the dysregulation of the host's response to infection rather than the direct consequences of the invading pathogen. Central to this initial immunologic response is the activation of leukocytes and microvascular endothelium resulting in cardiovascular instability, lung injury and renal dysfunction. Due to the primary role of leukocyte activation in the sepsis syndrome, a synthetic biomimetic membrane, called a selective cytopheretic device (SCD), was developed to bind activated leukocytes. The incorporation of the SCD along an extracorporeal blood circuit coupled with regional anticoagulation with citrate to lower blood ionized calcium was devised to modulate leukocyte activation in sepsis. Laboratory investigation. University of Michigan Medical School. Pigs weighing 30-35 kg. To assess the effect of the SCD in septic shock, pigs were administered 30×1010 bacteria/kg body weight of Escherichia coli into the peritoneal cavity and within 1 hr were immediately placed in an extracorporeal circuit containing SCD. In this animal model, the SCD with citrate compared to control groups without the SCD or with heparin anticoagulation ameliorated the cardiovascular instability and lung sequestration of activated leukocytes, reduced renal dysfunction and improved survival time compared to various control groups. This effect was associated with minimal elevations of systemic circulating neutrophil activation. These preclinical studies along with two favorable exploratory clinical trials form the basis of an FDA-approved investigational device exemption for a pivotal multicenter, randomized control trial currently underway.
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影响因子：
3
作者：
Humes, H. David;Sobota, Joseph T.;Song, Joon Ho
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13.2
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作者：
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