Corbett R J, Sterett R, Laptook A R
Department of Radiology (Ralph Rogers and Mary Nell Magnetic Resonance Center), University of Texas Southwestern Medical Center at Dallas 75235-9085.
J Neurochem. 1995 Jan;64(1):322-31. doi: 10.1046/j.1471-4159.1995.64010322.x.
Previously we have shown that hypercarbia produces a larger decrease in agonal glycolytic rate in 1-month-old swine than in newborns. In an effort to understand the mechanism responsible for this difference, we tested the hypothesis that hypercarbia produces age-related changes in the concentration of one or more effectors of phosphofructokinase activity. Specifically, in vivo 31P and 1H NMR spectroscopy was used to compare changes in lactate levels, intracellular pH, free magnesium concentration, and content of phosphorylated metabolites for these two age groups at three intervals during the first 1.5 min of complete ischemia in the presence or absence of hypercarbia (PaCO2 = 102-106 mm Hg). Hypercarbia produced the same drop in intracellular brain pH for both age groups, but the decrease in phosphocreatine level and increase in inorganic phosphate content were greater in 1-month-olds compared with newborns. During ischemia there was no difference between the magnitude of change in intracellular pH and levels of phosphocreatine and inorganic phosphate in hypercarbic 1-month-olds versus newborns. Under control conditions, i.e., normocarbia and normoxia, the free Mg2+ concentration was lower and the fraction of magnesium-free ATP was higher for newborns than 1-month-olds. However, there was no change in these variables for either age group during hypercarbia and early during ischemia. Thus, age-related differences in the relative decrease in agonal glycolytic rate during hypercarbia could not be explained by differences in intracellular pH, inorganic phosphate content, or free magnesium concentration. The [ADP]free at control was higher in newborns compared with 1-month-olds, and there was no age-related difference in [AMP]free. These variables did not change for newborns when exposed to hypercarbia, but for 1-month-olds [ADP]free and [AMP]free increased during hypercarbia relative to control values. High-energy phosphate utilization during ischemia for hypercarbic 1-month-olds was reduced by 74% compared with normocarbic 1-month-olds during ischemia, whereas the reduction in energy utilization (14%) was not significant for hypercarbic versus normocarbic newborns during ischemia.(ABSTRACT TRUNCATED AT 400 WORDS)
此前我们已经表明，与新生儿相比，高碳酸血症导致1月龄猪临死前糖酵解速率的下降幅度更大。为了理解造成这种差异的机制，我们检验了这样一个假设：高碳酸血症会使磷酸果糖激酶活性的一种或多种效应物的浓度产生与年龄相关的变化。具体而言，在存在或不存在高碳酸血症（动脉血二氧化碳分压=102 - 106 mmHg）的情况下，利用体内31P和1H核磁共振波谱技术，在完全缺血的最初1.5分钟内的三个时间点，比较这两个年龄组的乳酸水平、细胞内pH值、游离镁离子浓度以及磷酸化代谢产物含量的变化。高碳酸血症使两个年龄组的细胞内脑pH值下降幅度相同，但与新生儿相比，1月龄猪的磷酸肌酸水平下降幅度更大，无机磷酸盐含量增加幅度更大。在缺血期间，高碳酸血症的1月龄猪与新生儿相比，细胞内pH值以及磷酸肌酸和无机磷酸盐水平的变化幅度没有差异。在对照条件下，即正常碳酸血症和常氧状态下，新生儿的游离Mg2+浓度较低，无镁ATP的比例较高，高于1月龄猪。然而，在高碳酸血症期间和缺血早期，这两个年龄组的这些变量均无变化。因此，高碳酸血症期间临死前糖酵解速率相对下降的年龄相关差异，无法用细胞内pH值、无机磷酸盐含量或游离镁离子浓度的差异来解释。对照时，新生儿的游离[ADP]高于1月龄猪，游离[AMP]在两个年龄组之间没有与年龄相关的差异。新生儿暴露于高碳酸血症时，这些变量没有变化，但对于1月龄猪，高碳酸血症期间游离[ADP]和游离[AMP]相对于对照值增加。与缺血期间正常碳酸血症的1月龄猪相比，高碳酸血症的1月龄猪在缺血期间的高能磷酸盐利用率降低了74%，而与正常碳酸血症的新生儿相比，高碳酸血症的新生儿在缺血期间能量利用率的降低（14%）并不显著。（摘要截选至400字）
