Millis R M, Anonye C K, Reynolds M
Exp Neurol. 1987 Jan;95(1):235-48. doi: 10.1016/0014-4886(87)90021-5.
Many studies have shown increased affinity of hemoglobin for oxygen during metabolic alkalemia and dependence of intramitochondrial cytochrome oxidase activity on arterial oxyhemoglobin saturation. The present studies tested the hypothesis that metabolic alkalemia produces tissue hypoxia independent of arterial oxygen desaturation. Neuromuscular conduction latency was used as an indicator of functional impairment, and was measured following electrostimulation of the sciatic nerve and recording of the electromyogram from the gastrocnemius muscle of rats anesthetized with pentobarbital sodium. To increase the affinity of hemoglobin for oxygen, sodium bicarbonate was administered in graded doses every 15 min. Statistical significance of changes was estimated by the paired Student's t test. Arterial bicarbonate ion concentration increased from 25 +/- 1.3 to 39.0 +/- 3.0 mM while arterial pH increased from 7.30 +/- 0.02 to 7.50 +/- 0.03 (P less than 0.01). Neuromuscular conduction latency increased from 1.9 +/- 0.13 to 2.7 +/- 0.18 ms (P less than 0.01). Tissue hypoxia was suggested by a greater decrease in mass spectrometric determinations of gastrocnemius muscle oxygen tension (PO2) in separate groups of control (arterial pH 7.38 +/- 0.04) and experimental (arterial pH 7.48 +/- 0.03) rats. These changes were accompanied by markedly decreased uptake of 3.3'-diaminobenzidine (DAB) by gastrocnemius muscle mitochondria, suggesting decreased intracellular activity of cytochrome oxidase and intracellular oxygen availability to myocytes in the absence of arterial oxygen desaturation.
许多研究表明，在代谢性碱血症期间血红蛋白对氧的亲和力增加，并且线粒体内细胞色素氧化酶活性依赖于动脉氧合血红蛋白饱和度。本研究检验了以下假设：代谢性碱血症产生的组织缺氧与动脉血氧饱和度无关。神经肌肉传导潜伏期被用作功能损害的指标，在电刺激坐骨神经并记录用戊巴比妥钠麻醉的大鼠腓肠肌的肌电图后进行测量。为了增加血红蛋白对氧的亲和力，每隔15分钟给予不同剂量的碳酸氢钠。变化的统计学显著性通过配对学生t检验进行评估。动脉血碳酸氢根离子浓度从25±1.3 mM增加到39.0±3.0 mM，而动脉血pH从7.30±0.02增加到7.50±0.03（P<0.01）。神经肌肉传导潜伏期从1.9±0.13 ms增加到2.7±0.18 ms（P<0.01）。在单独的对照组（动脉血pH 7.38±0.04）和实验组（动脉血pH 7.48±0.03）大鼠中，腓肠肌氧分压（PO2）的质谱测定显示更大幅度的下降，提示组织缺氧。这些变化伴随着腓肠肌线粒体对3,3'-二氨基联苯胺（DAB）的摄取显著减少，表明在没有动脉血氧饱和度下降的情况下，细胞色素氧化酶的细胞内活性降低以及心肌细胞的细胞内氧供应减少。
