Simonson S G, Welty-Wolf K, Huang Y T, Griebel J A, Caplan M S, Fracica P J, Piantadosi C A
Department of Medicine, Duke University Medical Center, Durham, NC 27710.
Circ Shock. 1994 May;43(1):34-43.
Gram negative sepsis causes changes in oxygen supply-demand relationships. We have used a primate model of hyperdynamic gram negative sepsis produced by intravenous infusion of Escherichia coli (E. coli) to evaluate sepsis-induced alterations in mitochondrial oxidation-reduction (redox) state in muscle in vivo. The redox state of cytochrome a,a3, the terminal member of the intramitochondrial respiratory chain, was assessed in the intact forearm by near-infrared (NIR) spectroscopy. The muscle NIR data were compared to routine measures of oxygen delivery (DO2) and oxygen consumption (VO2). After E. coli infusion and fluid resuscitation, DO2 and VO2 showed minimal changes through 24 hr of sepsis. In contrast, changes in cytochrome a,a3 redox state evaluated by NIR occurred within a few hours and were progressive. Mitochondrial functional responses were correlated with structural changes observed on serial muscle biopsies. Gross morphological changes in muscle mitochondria were present in some animals as early as 12 hr, and, in most animals, by 24 hr. The morphologic changes were consistent with decreases in oxidative capacity as suggested by NIR spectroscopy. The NIR data also suggest that two mechanisms are operating to explain abnormalities in oxygen metabolism and mitochondrial function in lethal sepsis. These mechanisms include an early defect in oxygen provision to mitochondria that is followed by a progressive loss in functional cytochrome a,a3 in the muscle.
革兰氏阴性菌败血症会导致氧供需关系发生变化。我们使用了一种通过静脉输注大肠杆菌（E. coli）产生的高动力革兰氏阴性菌败血症灵长类动物模型，来评估败血症诱导的体内肌肉线粒体氧化还原状态的改变。通过近红外（NIR）光谱法在完整的前臂中评估线粒体内呼吸链末端成员细胞色素a,a3的氧化还原状态。将肌肉近红外数据与氧输送（DO2）和氧消耗（VO2）的常规测量值进行比较。在输注大肠杆菌并进行液体复苏后，在败血症的24小时内，DO2和VO2显示出最小的变化。相比之下，通过近红外评估的细胞色素a,a3氧化还原状态的变化在数小时内就会发生并且呈进行性。线粒体功能反应与在连续肌肉活检中观察到的结构变化相关。早在12小时时，一些动物的肌肉线粒体就出现了明显的形态学变化，而在大多数动物中，到24小时时出现了这种变化。形态学变化与近红外光谱法提示的氧化能力下降一致。近红外数据还表明，有两种机制在起作用，以解释致死性败血症中氧代谢和线粒体功能的异常。这些机制包括早期线粒体供氧缺陷，随后是肌肉中功能性细胞色素a,a3的逐渐丧失。
