Stability of brain intracellular lactate and 31P-metabolite levels at reduced intracellular pH during prolonged hypercapnia in rats.
Stability of brain intracellular lactate and 31P-metabolite levels at reduced intracellular pH during prolonged hypercapnia in rats.
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大鼠长期高碳酸血症期间细胞内 pH 值降低时脑细胞内乳酸和 31P 代谢物水平的稳定性。
DOI：
10.1038/jcbfm.1990.45
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发表时间：
1990
期刊：
影响因子：
--
通讯作者：
James,TL
中科院分区：
文献类型：
--
作者：
Cohen,Y;Chang,LH;Litt,L;Kim,F;Severinghaus,JW;Weinstein,PR;Davis,RL;Germano,I;James,TL
通过施加严重的、长时间的呼吸性酸中毒，在大鼠体内检查细胞内低pH值（pHi）的耐受性。将大鼠插管并在20%CO2下通气10 min，在50%CO2下通气75 min，在20%CO2下通气10 min。最大Paco 2为320 mm Hg。使用4.7-T水平仪器，用31 P和1H核磁共振（NMR）光谱在体内监测脑细胞内乳酸、pHi和高能磷酸盐代谢物。吸入50%CO_2后6 min内，pHifell下降0.57 ± 0.03单位，磷酸肌酸下降20%左右，Pi上升100%左右。这些值在高碳酸血症期的剩余时间内保持稳定。脑细胞内乳酸，可见与1H NMR光谱在高氧状态下，减少在高碳酸血症，这表明一个有利的变化，氧的可用性（减少乳酸产生）或增加乳酸清除或两者兼而有之。所有高碳酸血症动物在CO2停止后苏醒并表现正常。使用苏木精和伊红染色制备的皮质和海马区的组织学检查显示没有坏死区域，也没有神经胶质浸润。然而，在对照动物（未暴露于高碳酸血症）和高碳酸血症动物中均检测到孤立、分散、深染、萎缩的神经元。这种细微的组织学变化可能代表灌注-固定不完善导致的伪影，或者可能代表高碳酸血症方案期间的细微神经损伤。总之，如果维持充分的氧合，大鼠对极端高碳酸血症和低pHi（≤ 6.5）耐受良好，持续时间长达75分钟。高碳酸血症期间代谢物浓度的长期稳定性使得其便于用于pHi与脑损伤相关性的体内动物研究。
The tolerance of low intracellular pH (pHi) was examined in vivo in rats by imposing severe, prolonged respiratory acidosis. Rats were intubated and ventilated for 10 min with 20% CO2, for 75 min with 50% CO2, and for 10 min with 20% CO2. The maximum Paco2was 320 mm Hg. Cerebral intracellular lactate, pHi, and high-energy phosphate metabolites were monitored in vivo with31P and1H nuclear magnetic resonance (NMR) spectroscopy, using a 4.7-T horizontal instrument. Within 6 min after the administration of 50% CO2, pHifell by 0.57 ± 0.03 unit, phosphocreatine decreased by ∼20%, and Piincreased by ∼100%. These values were stable throughout the remainder of the hypercapnic period. Cerebral intracellular lactate, visible with1H NMR spectroscopy in the hyperoxic state, decreased during hypercapnia, suggesting either a favorable change in oxygen availability (decreased lactate production) or an increase in lactate clearance or both. All hypercapnic animals awakened and behaved normally after CO2was discontinued. Histological examination of cortical and hippocampal areas, prepared using a hematoxylin and eosin stain, showed no areas of necrosis and no glial infiltrates. However, isolated, scattered, dark-staining, shrunken neurons were detected both in control animals (no exposure to hypercapnia) and in animals that had been hypercapnic. This subtle histological change could represent an artifact resulting from imperfect perfusion-fixation, or it could represent subtle neurologic injury during the hypercapnia protocol. In summary, extreme hypercapnia and low pHi(∼6.5) are well tolerated in rats for periods up to 75 min if adequate oxygenation is maintained. The prolonged stability of metabolite concentrations during hypercapnia makes its use convenient for in vivo animal studies of the relevance of pHito brain injury.