Use of mitochondrial inhibitors to demonstrate that cytochrome oxidase near-infrared spectroscopy can measure mitochondrial dysfunction noninvasively in the brain
Use of mitochondrial inhibitors to demonstrate that cytochrome oxidase near-infrared spectroscopy can measure mitochondrial dysfunction noninvasively in the brain
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DOI：
10.1097/00004647-199901000-00003
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发表时间：
1999-01-01
影响因子：
6.3
通讯作者：
Delpy, DT
中科院分区：
文献类型：
--
作者：
Cooper, CE;Cope, M;Delpy, DT
使用近红外光谱法无创测量体内脑细胞色素氧化酶氧化还原状态的变化存在争议。因此，我们使用多波长检测器在新生猪脑中测试了这些测量结果。全氟化碳换血显示，新生猪、成年大鼠和纯化酶的近红外细胞色素氧化酶光谱是相同的。常氧条件下，新生猪脑含脱氧血红蛋白15μmol/L，氧合血红蛋白29μmol/L，氧化细胞色素氧化酶1.2μmol/L。使用线粒体抑制剂氰化物来确定在存在较大脑血红蛋白浓度的情况下是否可以检测到细胞色素氧化酶的氧化还原变化。添加氰化物可诱导带血和不带血动物的细胞色素氧化酶完全还原。在血液动物中，随后的缺氧导致血红蛋白氧合和浓度发生巨大变化，但不影响细胞色素氧化酶近红外信号。同时血氧水平依赖性磁共振成像测量结果显示与脱氧血红蛋白浓度的近红外测量结果具有良好的相关性。通过使用脑吸水率作为标准发色团同时测量光程长度，可以消除光散射变化对近红外测量的可能干扰。我们的结论是，在这些条件下，近红外光谱可以准确测量脑细胞色素氧化酶氧化还原状态的变化。
The use of near-infrared spectroscopy to measure noninvasively changes in the redox state of cerebral cytochrome oxidase in vivo is controversial. We therefore tested these measurements using a multiwavelength detector in the neonatal pig brain. Exchange transfusion with perfluorocarbons revealed that the spectrum of cytochrome oxidase in the near-infrared was identical in the neonatal pig, the adult rat, and in the purified enzyme. Under normoxic conditions, the neonatal pig brain contained 15 mu mol/L deoxyhemoglobin, 29 mu mol/L oxyhemoglobin, and 1.2 mu mol/L oxidized cytochrome oxidase. The mitochondrial inhibitor cyanide was used to determine whether redox changes in cytochrome oxidase could be detected in the presence of the larger cerebral hemoglobin concentration. Addition of cyanide induced full reduction of cytochrome oxidase in both blooded and bloodless animals. In the blooded animals, subsequent anoxia caused large changes in hemoglobin oxygenation and concentration but did not affect the cytochrome oxidase near-infrared signal. Simultaneous blood oxygenation level-dependent magnetic resonance imaging measurements showed a good correlation with near-infrared measurements of deoxyhemoglobin concentration. Possible interference in the near-infrared measurements from light scattering changes was discounted by simultaneous measurements of the optical pathlength using the cerebral water absorbance as a standard chromophore. We conclude that, under these conditions, near-infrared spectroscopy can accurately measure changes in the cerebral cytochrome oxidase redox state.