Cerebral metabolic response to low blood flow: possible role of cytochrome oxidase inhibition
Cerebral metabolic response to low blood flow: possible role of cytochrome oxidase inhibition
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DOI：
10.1038/sj.jcbfm.9600113
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发表时间：
2005-09-01
影响因子：
6.3
通讯作者：
Ostergaard, L
中科院分区：
文献类型：
--
作者：
Gjedde, A;Johannsen, P;Ostergaard, L
脑代谢对脑血流量(CBF)变化的反应还知之甚少。对神经元兴奋过程中CBF和氧耗不匹配(CMRO2)的一种常见解释是，血流增加比氧耗增加更多，以弥补脑线粒体缺乏氧气储备。相反，这一说法意味着，当血流量下降时，氧气消耗量必须下降。由于氧与细胞色素c氧化酶的主要反应速度与氧的张力有关，因此，这一主张旨在解释在过度换气(低碳酸血症)或环氧合酶(COX)抑制造成的CBF适度减少期间，氧气消耗是如何保持的。为了解决这一矛盾，我们扩展了以前发表的氧输送模型，增加了一个允许调节细胞色素C氧化酶对普遍存在的氧压力的亲和力的项。扩展的模型预测，在适度减少的血流量下，氧气消耗是恒定的。我们通过测定7名年轻健康志愿者的CBF和5名健康青年志愿者在COX抑制吲哚美辛前和期间的CMRO2，来确定扩展模型中细胞色素C氧化酶亲和力的变化。平均CBF下降了35%，而地区和平均CMRO2都没有明显变化。细胞色素C氧化酶亲和力对氧输送下降的调节可归因于一个假设因素，该因素具有与一氧化氮相同的几个性质。
The reactions of cerebral metabolism to imposed changes of cerebral blood flow (CBF) are poorly understood. A common explanation of the mismatched CBF and oxygen consumption (CMRO2) during neuronal excitation holds that blood flow rises more than oxygen consumption to compensate for an absent oxygen reserve in brain mitochondria. The claim conversely implies that oxygen consumption must decline when blood flow declines. As the prevailing rate of reaction of oxygen with cytochrome c oxidase is linked to the tension of oxygen, the claim falls to explain how oxygen consumption is maintained during moderate reductions of CBF imposed by hyperventilation (hypocapnia) or cyclooxygenase (COX) inhibition. To resolve this contradiction, we extended the previously published oxygen delivery model with a term allowing for the adjustment of the affinity of cytochrome c oxidase to a prevailing oxygen tension. The extended model predicted constant oxygen consumption at moderately reduced blood flow. We determined the change of affinity of cytochrome c oxidase in the extended model by measuring CBF in seven, and CMRO2 in five, young healthy volunteers before and during COX inhbition with indomethacin. The average CBF declined 35%, while neither regional nor average CMRO2 changed significantly. The adjustment of cytochrome c oxidase affinity to the declining oxygen delivery could be ascribed to a hypothetical factor with several properties in common with nitric oxide.