Evaluation of potential effectors of agonal glycolytic rate in developing brain measured in vivo by 31P and 1H nuclear magnetic resonance spectroscopy.
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)
Corbett
R J
RJ
Department of Radiology (Ralph Rogers and Mary Nell Magnetic Resonance Center), University of Texas Southwestern Medical Center at Dallas 75235-9085.
Sterett
R
R
Laptook
A R
AR
D000138:Acidosis / Q000378:metabolism / Q000503:physiopathology; D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism; D001921:Brain / Q000254:growth & development* / Q000378:metabolism*; D001923:Brain Chemistry; D003643:Death; D006003:Glycogen / Q000378:metabolism*; D006859:Hydrogen / Q000032:analysis*; D006863:Hydrogen-Ion Concentration; D006935:Hypercapnia / Q000378:metabolism / Q000503:physiopathology; D007511:Ischemia / Q000378:metabolism / Q000503:physiopathology; D007773:Lactates / Q000032:analysis / Q000378:metabolism; D008274:Magnesium / Q000032:analysis / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D010758:Phosphorus / Q000032:analysis*; D013552:Swine; D013556:Swine, Miniature
D007773:Lactates; D010758:Phosphorus; D006859:Hydrogen; D006003:Glycogen; D008274:Magnesium