Alterations in Mitochondrial Function in Blood Cells Obtained From Patients With Sepsis Presenting to an Emergency Department.

Alterations in Mitochondrial Function in Blood Cells Obtained From Patients With Sepsis Presenting to an Emergency Department.
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DOI:
10.1097/shk.0000000000001208
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发表时间:
2019-05
期刊:
Shock (Augusta, Ga.)
影响因子:
--
通讯作者:
Eckmann DM
Eckmann DM
中科院分区:
其他
文献类型:
--
作者:
Jang DH;Orloski CJ;Owiredu S;Shofer FS;Greenwood JC;Eckmann DM

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线粒体功能障碍被认为是脓毒症中导致器官功能障碍的关键细胞事件。我们的目标是测量早期脓毒症患者线粒体生物能量学的变化,以深入了解脓毒症中宿主反应失调的不完全理解的病理生理学。前瞻性观察性研究单站点三级学术急诊科我们共纳入48名受试者,10名败血症或脓毒性休克,10名感染无败血症,14名老年人和14名年轻人健康对照。采用高分辨率呼吸仪(OROBOROS O2K)检测外周血单个核细胞(PBMCs)。脓毒症、单纯感染、老年对照组和年轻对照组的中位年龄分别为63岁、34岁、61岁和39岁。脓毒症组第1小时SOFA评分中位数为8,初始乳酸中位数为4.2 mmol/dL,而感染组为1.1。脓毒症/感染性休克组30天死亡率为50%,中位住院时间为7天。与其他组相比,脓毒症组的常规呼吸和最大呼吸以及未偶联的复合体I呼吸显著降低。与另一组相比,脓毒症组的atp相关呼吸和备用储备能力也显著下降。在老年对照组和年轻对照组之间没有年龄相关的呼吸差异。床边测量线粒体呼吸可以是微创的,并且可以及时进行。线粒体功能障碍,通过减少用于能量生产的氧气消耗和耗尽细胞生物能量储备来检测。
Mitochondrial dysfunction has been implicated as a key cellular event leading to organ dysfunction in sepsis. Our objective is to measure changes in mitochondrial bioenergetics in subjects with early presentation of sepsis to provide insight into the incompletely understood pathophysiology of the dysregulated host response in sepsis. Prospective observational study Single site tertiary academic emergency department We enrolled a total of 48 subjects were enrolled in the study, 10 with sepsis or septic shock, 10 with infection without sepsis, 14 older and 14 younger healthy controls. Peripheral blood mononuclear cells (PBMCs) were measured with high-resolution respirometry (OROBOROS O2K). The median age in patients with sepsis, infection only, older control and younger controls were 63, 34, 61, and 39 years old, respectively. In the Sepsis group, the median 1st 24-hour SOFA score was 8, and the initial median lactate was 4.2 mmol/dL, compared to 1.1 in the Infection Group. The 30-day mortality of the sepsis/septic shock group was 50%, with a median length of stay of 7-days. The Sepsis Group had significantly lower routine and Max respiration when compared to the other groups as well as uncoupled Complex I respiration. There was also a significant decrease in ATP-linked respiration along with the Spare Reserve Capacity in the Sepsis Group when compared to the other group. There were no age-related differences in respiration between the Older and Younger control group. Bedside measurement of mitochondrial respiration can be minimally invasive and performed in a timely manner. Mitochondrial dysfunction, detected by decreased oxygen consumption utilized for energy production and depleted cellular bioenergetics reserve.