Exposure to moderate hypoxia in humans leads to cerebral lactate production, which occurs even when the cerebral metabolic rate of oxygen (CMRO2) is unaffected. We searched for the mechanism of this lactate production by testing the hypothesis of upregulation of cerebral glycolysis mediated by hypoxic sensing. Describing the pathways counteracting brain hypoxia could help us understand brain diseases associated with hypoxia. A total of 65 subjects participated in this study: 30 subjects were exposed to poikilocapnic hypoxia, 14 were exposed to isocapnic hypoxia, and 21 were exposed to carbon monoxide (CO). Using this setup, we examined whether lactate production reacts to an overall reduction in arterial oxygen concentration or solely to reduced arterial oxygen partial pressure. We measured cerebral blood flow (CBF), CMRO2, and lactate concentrations by magnetic resonance imaging and spectroscopy. CBF increased (P < 10−4), whereas the CMRO2 remained unaffected (P > 0.076) in all groups, as expected. Lactate increased in groups inhaling hypoxic air (poikilocapnic hypoxia: $0.0136\ \frac{\mathrm{mmol}/\mathrm{L}}{\Delta{\mathrm{S}}_{\mathrm{a}}{\mathrm{O}}_2}$, P < 10−6; isocapnic hypoxia: $0.0142\ \frac{\mathrm{mmol}/\mathrm{L}}{\Delta{\mathrm{S}}_{\mathrm{a}}{\mathrm{O}}_2}$, P = 0.003) but was unaffected by CO (P = 0.36). Lactate production was not associated with reduced CMRO2. These results point toward a mechanism of lactate production by upregulation of glycolysis mediated by sensing a reduced arterial oxygen pressure. The released lactate may act as a signaling molecule engaged in vasodilation.

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人脑灌注、耗氧量和乳酸生成以应对缺氧暴露

人类暴露于中度缺氧会导致脑乳酸产生，即使在脑氧代谢率 (CMRO2) 不受影响时也会发生这种情况。我们通过测试由缺氧感应介导的脑糖酵解上调的假设来寻找这种乳酸产生的机制。描述对抗脑缺氧的途径可以帮助我们了解与缺氧相关的脑部疾病。共有 65 名受试者参与了这项研究：30 名受试者暴露于异碳酸缺氧环境中，14 名受试者暴露于等二氧化碳低氧环境中，21 名受试者暴露于一氧化碳 (CO) 环境中。使用这种设置，我们检查了乳酸的产生是否对动脉氧浓度的总体降低或仅对动脉氧分压的降低有反应。我们测量了脑血流量 (CBF)、CMRO2、和乳酸浓度通过磁共振成像和光谱。正如预期的那样，所有组的 CBF 增加 (P < 10-4)，而 CMRO2 保持不受影响 (P > 0.076)。吸入低氧空气的组乳酸增加（poikilocapnic 低氧：$0.0136\ \frac{\mathrm{mmol}/\mathrm{L}}{\Delta{\mathrm{S}}_{\mathrm{a}}{\mathrm{ O}}_2}$, P < 10−6；等碳酸性缺氧：$0.0142\ \frac{\mathrm{mmol}/\mathrm{L}}{\Delta{\mathrm{S}}_{\mathrm{a }}{\mathrm{O}}_2}$, P = 0.003）但不受 CO 的影响（P = 0.36）。乳酸产生与减少的 CMRO2 无关。这些结果指出了通过感知降低的动脉氧压介导的糖酵解上调产生乳酸的机制。释放的乳酸可以作为参与血管舒张的信号分子。