Non-Invasive Investigation of Cerebral Metabolism in Newborn Infants by Phosphorus Nuclear Magnetic Resonance Spectroscopy

Cady, Ernest B.; Dawson, M. Joan; Hope, Peter; Tofts, Paul S.; Costello, A.; Delpy, David T.; Reynolds, E. O. R.; Wilkie, D.

doi:10.1016/s0140-6736(83)91906-2

Cited by 279 publications

(70 citation statements)

References 15 publications

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“…The PCr/Pi ratio in the infant rabbit is 2.26, sim ilar to the value of 1.7 measured by Cady et al (1983) in human infants and less than that measured by L. Litt et al (unpublished observation) in adult rats (Table 1). The P/ATP ratio in the infant rabbit brain of 0.38 is not significantly different from the values in adult rats and rabbits of 0.6 (Table 1).…”

Section: Discussioncontrasting

confidence: 38%

Effects of Hypoxic Hypoxia on Cerebral Phosphate Metabolites and pH in the Anesthetized Infant Rabbit

González‐Méndez

McNeill

Gregory

et al. 1985

J Cereb Blood Flow Metab

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Summary:The effects of hypoxic hypoxia on high-en ergy phosphate metabolites and intracellular pH (pH) in the brain of the anesthetized infant rabbit were studied in vivo using 31p nuclear magnetic resonance spectros copy. Five 10c to 16-day-old rabbits were anesthetized with 1.5% halothane. Ventilation was controlled to main tain normocarbia . Inspired 07 fraction was adjusted to produce three states of arterial oxygenation: hyperoxia (Pao2 > 250 mm Hg), normoxia (Pao2 �100 mm Hg), and hypoxia (Pao2 25-30 mm Hg). During hypoxia, blood pressure was kept within 20% of control values with a venous infusion of epinephrine. During hyperoxia, the phosphocreatine-to-ATP ratio was 0.86, a value that is 2-2.5 times less than that reported for adults. During norNeonates survive longer periods of anoxia than adults of the same species. Similarly, hypoxic ne onates sustain less central nervous system injury than adults (Dawes, 1968). This cannot be explained by a more efficient oxygen delivery system or ce rebrovascular response (Koehler et aI., 1984). It is possible that neonates have a better neurologic out come after oxygen deprivation because their cere bral energy stores are maintained more effectively than in adults. Duffy et al. (1975) used freeze extraction to mea sure cerebral phosphocreatine (PCr) and ATP in newborn and older rats and found that PCr levels were higher in the latter. They also found that global 512 moxia, ATP decreased by 20% and Pi increased by 90% from hyperoxia values. During 60 min of hypoxia, the concentrations of high-energy phosphate metabolites did not change, but intracellular and arterial blood pH (pH) decreased significantly. When hyperoxia was reestab lished, pHi returned to normal and pHa remained low. These results suggest that during periods of hypoxemia, the normotensive infant rabbit maintains intracellular concentrations of cerebral high-energy phosphates better than has been reported for adult animals. Key Words: Brain metabolism-Halothane anesthesia-Hypoxic hypoxia-Infant rabbit-In ViVO_31p nuclear magnetic resonance.ischemia depleted ATP and PCr levels more rapidly in the brain of older animals. Norwood et al. (1979) used 31 p nuclear magnetic resonance (NMR) spec troscopy to study the perfused neonatal rat brain and found the PCr signal intensity to be approxi mately the same as the ATP signal intensity. The brain PCr/ATP ratio seen by 31 p NMR in normal human infants was also � 1.0 (Cady et aI., 1983). Norwood et al. (1983) calculated the half-life of PCr in the ischemic brain to be 7.5 min in the neonate and 3.3 min in the adult, confirming the earlier work of Duffy et al. (1975).We have studied the effects of hypoxic hypoxia on cerebral intracellular phosphate metabolites and on intracellular pH (pH) in anesthetized normoten sive infant rabbits. This study, performed in vivo using 31 p NMR, shows that arterial oxygen tensions that provoke changes in intracellular phosphate me tabolite concentrations in the brain of the adult an imal do not produce these changes in the brai...

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Section: Discussioncontrasting

confidence: 38%

Effects of Hypoxic Hypoxia on Cerebral Phosphate Metabolites and pH in the Anesthetized Infant Rabbit

González‐Méndez

McNeill

Gregory

et al. 1985

J Cereb Blood Flow Metab

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“…Jensen et al (4 ) developed a MS/MS method for neonatal screening for galactosemia based on the presence of increased intracellular concentrations of galactose 1-phosphate. Other studies reported accumulation of ribo-5P in human infant brain (9 ) and in tumor cells (10 ).…”

Section: Discussionmentioning

confidence: 87%

Profiling of Pentose Phosphate Pathway Intermediates in Blood Spots by Tandem Mass Spectrometry: Application to Transaldolase Deficiency

et al. 2003

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Background:Recently, several patients with abnormal polyol profiles in body fluids have been reported, but the origins of these polyols are unknown. We hypothesized that they are derived from sugar phosphate intermediates of the pentose phosphate pathway (PPP), and we developed a semiquantitative method for profiling of pentose phosphate pathway intermediates. Methods: Sugar phosphates in blood spots were simultaneously analyzed by liquid chromatography-tandem mass spectrometry using an ion-pair-loaded C 18 HPLC column. The tandem mass spectrometer was operated in the multiple-reaction monitoring mode. Enzymatically prepared D-[ 13 C 6 ]glucose 6-phosphate was used as internal standard. The method was used to study sugar phosphates abnormalities in a patient affected with a deficiency of transaldolase (TALDO1; EC 2.2.1.2). Results: In control blood spots, dihydroxyacetone phosphate, pentulose 5-phosphates, pentose 5-phosphates, hexose 6-phosphates, and sedoheptulose 7-phosphate were detected. Detection limits ranged from ϳ100 to ϳ500 nmol/L. Glyceraldehyde 3-phosphate and erythrose 4-phosphate were undetectable. Intra-and interassay imprecision (CVs) were 10 -17% and 12-21%, respectively. In blood from the TALDO1-deficient patient, sedoheptulose 7-phosphate was increased.

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“…Recently, the brains of new-born infants have been examined (Cady, Costello, Dawson, Delpy, Hope, Reynolds, Tofts& Wilkie, 1983 babies, low ratios of PCr/P1 (<08), were found to be associated with a very bad prognosis for survival and early neurodevelopmental outcome (Hope, Costello, Cady, Delpy, Tofts, Chu, Hamilton, Reynolds & Wilkie, 1984). The spectra from human infant brains differed from those found previously for animal brains (e.g.…”

Section: Introductionmentioning

confidence: 92%

Changes in brain phosphorus metabolites during the post‐natal development of the rat.

Tofts¹,

Wray²

1985

The Journal of Physiology

100

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SUMMARY1. Changes in brain phosphorus metabolites during the post-natal development of the rat and in neonatal and adult guinea-pigs have been studied in vivo using 31P nuclear magnetic resonance spectroscopy (n.m.r.s.).2. The brain spectra showed clear differences with age, particularly during the first 3 weeks post-partum.3. The spectra from 4-day-old rats resembled those of new-born human infants. We suggest that the differences between human and animal brains seen in previously published spectra arise because of an age difference rather than a species difference.4. The phosphocreatine (PCr) to nucleoside triphosphate (NTP) ratio increased from around 1-0 in 3-day-old rats to 1P8 in adult animals. The adult ratio is larger than that previously reported from in vitro chemical analyses.5. An unknown compound in the phosphomonoester (PME) region of the spectra predominated in young animals, but decreased in concentration relative to NTP with age and reached adult values by around 2 weeks post-partum.6. Neonatal guinea-pigs, which are much more developed at birth than the rat, had a significantly greater PCr/NTP ratio than the neonatal rat, but their brain spectra also contained the large PME peak.7. The intracellular pH of cerebral tissue was estimated to be 7-21 +0-02 and did not show any change with age.8. The changes we find in the phosphorus compounds in the brain may be of importance in post-natal development, and the possible functional significance of these results is discussed.

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Non-Invasive Investigation of Cerebral Metabolism in Newborn Infants by Phosphorus Nuclear Magnetic Resonance Spectroscopy

Cited by 279 publications

References 15 publications

Effects of Hypoxic Hypoxia on Cerebral Phosphate Metabolites and pH in the Anesthetized Infant Rabbit

Effects of Hypoxic Hypoxia on Cerebral Phosphate Metabolites and pH in the Anesthetized Infant Rabbit

Profiling of Pentose Phosphate Pathway Intermediates in Blood Spots by Tandem Mass Spectrometry: Application to Transaldolase Deficiency

Changes in brain phosphorus metabolites during the post‐natal development of the rat.

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