Evaluation of Potential Effectors of Agonal Glycolytic Rate in Developing Brain Measured In Vivo by ³¹P and ¹H Nuclear Magnetic Resonance Spectroscopy

Abstract

Previously we have shown that hypercarbia produces a larger decrease in agonal glycolytic rate in 1month-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 3 'P and 'H 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 Mg 2 + 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 1month-olds [ADP]free and [AMP]free increased during hypercarbia relative to control values . High-energy phosphate utilization during ischemia for hypercarbic 1month-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 . Because hypercarbia reduces the rate of ATP depletion during ischemia in 1-month-olds to a greater extent than in newborns, the increase in [ADP]free and [AMP]free will be slower in the former age group. It follows 322 therefore that for 1-month-olds, the agonal glycolytic rate would not be accelerated by ADP and AMP to the same degree during hypercarbia plus ischemia compared with normocarbic plus ischemia, whereas for newborns hypercarbia has relatively little impact on agonal glycolytic rate .

Brain Temperature Measured Using Proton MR Spectroscopy Detects Cerebral Hemodynamic Impairment in Patients With Unilateral Chronic Major Cerebral Artery Steno-Occlusive Disease

“…8 -11 Experimental studies in phantoms 12 and experimental models 12 have shown close correlations between temperature as measured by MRS and implanted probes. MRS has also been used to measure brain temperature (BT) in healthy adult human volunteers, 9 infants, 8 and patients with brain tumors 10 and acute ischemic stroke.…”

Brain Changes to Hypocapnia Using Rapidly Interleaved Phosphorus-Proton Magnetic Resonance Spectroscopy at 4 T

“…Further, when comparing newborn and 1-month old piglets response to hypoxia (18 mins), an equivalent magnitude of PCr decrease (63%) is observed, suggesting that the energetic systems are similarly vulnerable to such an insult (Corbett et al , 1996). For some challenges, such as hypercarbia, younger age may be an advantage (Corbett et al , 1995), owing to newborn piglets having an enhanced resiliency for acid clearance (Corbett et al , 1999).…”