OXIDANT STRESS RESPONSES IN PREMATURE-INFANTS DURING EXPOSURE TO HYPEROXIA
OXIDANT STRESS RESPONSES IN PREMATURE-INFANTS DURING EXPOSURE TO HYPEROXIA
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DOI：
10.1203/00006450-199309000-00024
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发表时间：
1993-09-01
影响因子：
3.6
通讯作者：
ELLIOTT, SJ
中科院分区：
文献类型：
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作者：
SMITH, CV;HANSEN, TN;ELLIOTT, SJ
为了评估新生儿接受高浓度氧治疗后的氧化应激反应，我们测定了胎龄为23至42周的新生儿血浆谷胱甘肽（GSH）和谷胱甘肽二硫化物（GSSG）浓度。所有参与研究的婴儿都接受了机械通气，并在他们的脐动脉中放置了导管，作为他们正常临床管理的一部分。在第1、3和5天采集血样，此后每周采集一次或直至导管取出。我们观察到这些婴儿的GSSG血浆浓度通常比我们在成人中发现的0.1至0.3 μ M高一个数量级。有趣的是，血浆GSSG浓度与吸入氧张力呈负相关。这种影响似乎是由于患者选择标准造成的，在研究的婴儿中，那些呼吸最低氧分压的婴儿是最小的，也是最年轻的。第二个观察结果是早产儿的GSH血浆浓度比我们在成年人中观察到的（6 - 10 μ M）低很多，实际上经常是显著的。最后，我们发现，在脐动脉和脐静脉导管的患者动脉GSSG浓度始终高于静脉浓度;相反，动脉GSH浓度低于静脉浓度。我们在这些婴儿中观察到的升高的GSSG浓度表明早产儿有明显的氧化应激反应，即使是那些只暴露在室内空气中的婴儿。这些婴儿的肺中GSSG浓度的正动静脉梯度表明，至少有一些增加的血浆GSSG起源于肺。我们在这些婴儿中观察到的低血浆GSH浓度表明，在许多动物研究中已经显示出的抗氧化剂的缺陷是预防高氧诱导的肺损伤的关键。最后，GSH浓度在肺内的负动静脉梯度提供了人类肺摄取GSH的第一个证据。
To assess oxidant stress responses in newborn infants treated with elevated concentrations of oxygen, we measured plasma concentrations of glutathione (GSH) and glutathione disulfide (GSSG) in newborn infants ranging from 23 to 42 wk gestational age. All infants recruited into the study were mechanically ventilated and had catheters placed in their umbilical arteries as part of their normal clinical management. Blood samples were obtained on d 1, 3, and 5 and weekly thereafter or until the catheters were removed. We observed plasma concentrations of GSSG in these infants that were frequently an order of magnitude higher than the 0.1 to 0.3 muM we find in adults. Interestingly, plasma GSSG concentrations were inversely correlated to the inspired oxygen tensions. This effect appeared to arise from the patient selection criteria whereby, of the infants studied, those breathing the lowest partial pressures of oxygen were the smallest and gestationally youngest. A second observation was that plasma concentrations of GSH in the premature infants were substantially, indeed often dramatically, lower than we have observed in adult humans (6 to 10 muM). Finally, we found that in patients with both umbilical arterial and umbilical venous catheters arterial GSSG concentrations were consistently higher than venous concentrations; conversely, arterial GSH concentrations were lower than venous concentrations. The elevated GSSG concentrations we observed in these infants indicate marked oxidant stress responses in prematurely born infants, even in those infants exposed only to room air. The positive arteriovenous gradients of GSSG concentrations across the lungs of these infants suggest that at least some of the increased plasma GSSG originates in the lung. The low plasma GSH concentrations we observed in these same infants suggest deficiencies in an antioxidant that has been shown in numerous animal studies to be critical for prevention of hyperoxia-induced lung injury. Finally, the negative arteriovenous gradients of GSH concentrations across the lung provide the first evidence in humans for pulmonary uptake of GSH.