phosphocreatine and Asphyxia-Neonatorum

To evaluate the effects of creatine phosphate (CP) in the treatment of myocardial damage following neonatal asphyxia.. Medical databases were searched for a systematic literature review and meta-analysis of randomized and quasi-randomized trials on the treatment of myocardial damage with CP following neonatal asphyxia. The data was analyzed using Review Manager 5.1.. Six trials involving 400 patients (CP treatment/control: 202/198) were included in the survey. The meta-analysis indicated that CP treatment for 7 days decreased serum myocardial enzyme levels (CK, CK-MB, LDH, HBDH and cTnI levels). Both the total effective rate (RR: 1.29; 95% CI: 1.12, 1.48) and the significantly effective rate (RR: 1.78; 95% CI: 1.32, 2.41) in the CP treatment group were significantly higher than in the control group. CP treatment reduced the hospitalization period by 4.07 days compared with the control group (95% CI: -5.25, -2.89).. CP treatment appears to be more effective than routine treatment alone for myocardial damage following neonatal asphyxia. It appears to be safe and it can both decrease serum myocardial enzyme levels and shorten the period of hospitalization. However, as the evidence obtained in this study is not robust due to the poor quality of current studies, further studies of high-quality, large-scale trails are needed.

Topics: Asphyxia Neonatorum; Cardiomyopathies; Cardiotonic Agents; Humans; Infant, Newborn; Length of Stay; Myocytes, Cardiac; Phosphocreatine; Randomized Controlled Trials as Topic

It is difficult to predict the neurologic outcome of neonates with hypoxic-ischemic encephalopathy (HIE). Our goal was to investigate the prognostic values of magnetic resonance spectroscopy (MRS) in neonatal HIE. During this study, 46 neonates with HIE underwent magnetic resonance imaging (MRI) and proton MRS ((1)HMRS). The sample included 25 cases of mild HIE, 11 cases of moderate HIE, and 10 cases of severe HIE. Nine healthy neonates without asphyxia served as controls. (1)HMRS techniques included single-voxel MRS and 2-D-point-resolved spatially localized spectroscopy (PRESS) multivoxel chemical shift spectroscopy imaging. Then, 31 of 46 neonates with HIE were divided into 3 groups according to their prognosis: dead, abnormal, and normal outcome. Abnormal and normal outcome were defined by follow-up MRI. Metabolic changes were analyzed and compared with HIE grading and prognosis. As a result, the GLx-alpha peak was markedly increased in the moderate and severe HIE groups. The GLx-alpha/Cr ratio in the control, mild, moderate, and severe HIE groups was 0.18, 0.21, 0.64, 1.31, respectively. The Lac/Cr ratio was 0.12, 0.14, 0.19, and 0.26, respectively. A Spearman rank correlation test confirmed that the ratio of GLx-alpha/Cr and Lac/Cr had significant positive correlation with clinical grading of HIE (P < 0.01). The GLx-alpha/Cr ratio in the dead, abnormal, and normal outcome groups was 1.28, 0.82, and 0.25, respectively; the Lac/Cr ratio was 0.34, 0.19, and 0.14, respectively. An anaylsis of variance demonstrated that the differences were significant (both P < 0.01). A Spearman rank correlation test confirmed that the ratio of GLx-alpha/Cr and Lac/Cr had significant negative correlation with prognosis of HIE; GLx-alpha/Cr showed a much stronger correlation than the Lac/Cr ratio (P < 0.01). The formula of the relationship between the poor prognosis of HIE and the ratio of GLx-alpha/Cr in basal ganglia was established by the logistic regression model. In conclusion, (1)HMRS is a useful tool for evaluating the severity and prognosis of HIE. The higher ratio of GLx-alpha/Cr in the basal ganglia and thalamus may predict a poor outcome in neonates with HIE.

Topics: Asphyxia Neonatorum; Basal Ganglia; Choline; Creatine; Female; Follow-Up Studies; Glutamic Acid; Glutamine; Humans; Hypoxia-Ischemia, Brain; Infant, Newborn; Logistic Models; Magnetic Resonance Spectroscopy; Male; Phosphocreatine; Predictive Value of Tests; Prognosis; Protons; Severity of Illness Index; Thalamus

Previous studies have shown that poly (ADP-ribose) polymerase (PARP) and DNA polymerase beta, nuclear enzymes, are associated with cell replication and DNA repair. The present study tests the hypothesis that hypoxia results in increased PARP and DNA polymerase activity in cerebral cortical neuronal nuclei to repair the hypoxia-induced damage to genomic DNA. Studies were conducted in 13 anesthetized and ventilated newborn piglets (age 3-5 days) divided into normoxic (n=5) and hypoxic (n=8) groups. Hypoxia was induced by decreasing inspired oxygen from 21% to 7% for 60 min. Cerebral tissue hypoxia was documented biochemically by determining the tissue levels of ATP and phosphocreatine (PCr). Following isolation of the cortical neuronal nuclei, the activity of PARP and DNA polymerase beta was determined. During hypoxia, the tissue ATP level decreased by 73% from 4.12+/-0.67 micromol/g brain to 1.12+/-0.34 micromol/g brain, and PCr decreased by 78% from 4.14+/-0.68-0.90+/-0.20 micromol/g brain. In hypoxic neuronal nuclei, PARP activity significantly increased from 5.88+/-0.51 pmol NAD/mg protein/h in normoxic nuclei to 10.04+/-2.02 (P=0.001). PARP activity inversely correlated with tissue ATP (r=0.78) and PCr levels (r=0.81). Administration of N-nitro-L-arginine prior to hypoxia decreased the hypoxia-induced increase in PARP activity by 67%. Endogenous DNA polymerase beta activity increased from 0.96+/-0.13 in normoxic nuclei to 1.39+/-0.18 nmol/mg protein/h in hypoxic nuclei (P<0.005). DNA polymerase beta activity in the presence of exogenous template increased from 1.54+/-0.14 in the normoxic to 2.42+/-0.26 nmol/mg protein/h in the hypoxic group (P<0.005). DNA polymerase beta activity in the presence or absence of template inversely correlated with the tissue ATP (r=0.95 and 0.84, respectively) and PCr levels (r=0.93 and 0.77, respectively). These results demonstrate that the activity of PARP and DNA polymerase beta enzymes increase with the increase in degree of cerebral tissue hypoxia. Furthermore, the results demonstrate a direct correlation between the PARP and the DNA polymerase beta activity. We conclude that tissue hypoxia results in increased PARP and DNA polymerase beta activities indicating activation of DNA repair mechanisms that may result in potential neuronal recovery following hypoxia and the hypoxia-induced increase in PARP activity is NO-mediated.

Topics: Adenosine Triphosphate; Animals; Asphyxia Neonatorum; Cell Nucleus; Cerebral Cortex; DNA Damage; DNA Polymerase beta; DNA Repair; Enzyme Inhibitors; Humans; Hypoxia, Brain; Infant, Newborn; NAD; Nerve Degeneration; Neurons; Nitric Oxide; Nitroarginine; Phosphocreatine; Poly(ADP-ribose) Polymerases; Recovery of Function; Sus scrofa; Up-Regulation

Previous studies have shown that hypoxia results in the generation of nitric oxide (NO) free radicals in the cerebral cortex of newborn animals. The present study tested the hypothesis that NO increases Ca++-influx in neuronal nuclei as well as N-methyl-D aspartate (NMDA) receptor-mediated Ca++-influx in cortical synaptosomes of newborn piglets. Studies were performed in five normoxic (Nx) and 6 hypoxic (Hx) newborn piglets. Cerebral tissue hypoxia was documented by determining the levels of ATP and phosphocreatine (PCr). 45Ca++ -influx was determined in the presence of sodium nitroprusside (SNP, 10 microM), a NO donor, and peroxynitrite (10 microM). In the Hx group, ATP levels decreased to 1.40+or-0.69 vs 4.27+or-0.80 micromoles/g brain in the Nx group (P<0.05). Similarly, PCr levels decreased to 0.91+or-0.57 vs 3.40+or-0.99 micromoles/g brain (P<0.001). Nuclear 45Ca++-influx increased from 3.57+or-1.46 pmoles/mg protein in Nx nuclei to 8.64+or-3.50 in Hx nuclei (P<0.05). SNP increased neuronal nuclear Ca++ influx in the Nx from 3.57+or-1.46 to 5.47+or-2.52 pmoles/mg protein (P<0.05) but did not affect Ca++ influx in the Hx group (8.64+or-3.50 vs. 10.17+or-4.00 pmoles/mg protein). The level of Ca++ influx in the presence of SNP in Nx nuclei was similar to that seen in Hx nuclei alone. Peroxynitrite did not affect nuclear Ca++-influx in either Nx or Hx group. Synaptosomal Ca++-influx in the presence of glu + gly was 40+or-11 pmoles/mg protein in the Nx group and 80+or-16 pmoles/mg protein in the Hx group (P<0.05). Both SNP and peroxynitrite increased Ca++ influx in Nx and Hx synaptosomes. These results show that hypoxia results in increased nuclear and synaptosomal Ca++-influx. Further, the data demonstrate that NO increases intranuclear as well as intrasynaptosomal Ca++-influx and suggest that during hypoxia, the increase in intranuclear and intraynaptosomal Ca++ is NO-mediated. We propose that NO-mediated modification (by nitrosylation/nitration) of nuclear membrane high affinity Ca++-ATPase and neuronal membrane NMDA receptor, resulting in increased intranuclear and intracellular Ca++ influx, are potential NO-mediated mechanisms of Hx neuronal injury.

Topics: Adenosine Triphosphate; Animals; Asphyxia Neonatorum; Calcium; Calcium Signaling; Cell Nucleus; Cerebral Cortex; Free Radicals; Glutamic Acid; Glycine; Humans; Hypoxia, Brain; Infant, Newborn; Nerve Degeneration; Neurons; Nitric Oxide; Nitric Oxide Donors; Oxidative Stress; Peroxynitrous Acid; Phosphocreatine; Receptors, N-Methyl-D-Aspartate; Swine; Synaptosomes

The aim of the study was to test the hypotheses that elevated cerebral lactate, detected by proton spectroscopy performed within 18 hours of suspected birth asphyxia, is associated with adverse outcome, and that increased lactate can be used to predict adverse outcome. Thirty-one term infants suspected of having had birth asphyxia and seven control infants underwent proton magnetic resonance spectroscopy, using three-dimensional chemical shift imaging, within 18 hours of birth. Adverse outcome was defined as death or neurodevelopmental impairment at 1 year of age or more. Nine infants had an adverse outcome. The other 22 and all of the control infants remained normal. Median (range) lactate/creatine plus phosphocreatine (lactate/creatine) ratios in the abnormal, the normal, and the control group were 1.14 (0.17 to 3.81), 0.33 (0 to 1.51), and 0.05 (0 to 0.6) respectively (P=0.003). Lactate/creatine >1.0 predicted neurodevelopmental impairment at 1 year of age with sensitivity of 66% and specificity of 95%, positive and negative predictive values of 86% and 88%, and a likelihood ratio of 13.2. Elevated cerebral lactate/creatine within 18 hours of birth asphyxia predicts adverse outcome.

Topics: Asphyxia Neonatorum; Brain; Brain Damage, Chronic; Creatine; Female; Humans; Image Processing, Computer-Assisted; Infant; Infant, Newborn; Lactic Acid; Magnetic Resonance Spectroscopy; Male; Phosphocreatine; Pregnancy; Sensitivity and Specificity

Brain metabolite levels are measured by proton magnetic resonance spectroscopy (1H MRS) and include N-acetylaspartate (NAA), creatine (Cr), choline (Cho), and lactate and the ratios NAA to Cho and Cr (NAA-ChoCr), NAA-Cr, NAA-Cho, and Cho-Cr. Brain metabolite levels may correlate with the degree of neonatal asphyxia.. To determine which brain metabolite ratios have the strongest correlation with the Apgar scores in infants with possible asphyxia; whether the correlation is stronger with basal ganglia (BG) or anterior border-zone metabolites; and whether a combined approach using routine MR imaging (MRI), diffusion-weighted MRI, and MRS can be used to evaluate the severity of neonatal asphyxia.. Twenty infants with 1-minute Apgar scores of 6 or less were studied at 2 to 28 days of age. The MRS variables were compared with routine and diffusion-weighted brain MRI. Clinical variables and MRS findings were subjected to factor analysis and stepwise multiple regressions to determine interrelationships.. The BG region NAA-Cho and NAA-ChoCr ratios correlated with the 1-minute (P<.001) and 5-minute (P = .01 for NAA-Cho; P = .006 for NAA-ChoCr). There was no correlation between metabolite levels and the 10-minute Apgar scores. The stongest predictions exist between the 1-minute Apgar scores and the NAA-Cho and NAA-ChoCr ratios. In the anterior border zone, the only correlation was between the 1-minute Apgar score and the NAA-Cho ratio, but there was a strong age effect in these data. Lactate was found in the BG of 3 infants, all of whom had 5-minute Apgar scores of 6 or less. Three patients had focal lesions on MRI; 2 of these had elevated lactate levels in the abnormal region; and the third, who had an intrauterine stroke, had no lactate in the region.. Correlations between NAA-Cho and NAA-ChoCr ratios and the 1- and 5-minute Apgar scores are stronger in the BG region than in the frontal border zone. The presence or absence of lactate may indicate the severity of the brain insult, and the combination of MRS, MRI, and diffusion-weighted MRI may assist in localizing and predicting a long-term brain injury.

Topics: Apgar Score; Aspartic Acid; Asphyxia Neonatorum; Basal Ganglia; Cerebral Palsy; Choline; Humans; Infant, Newborn; Lactic Acid; Magnetic Resonance Imaging; Phosphocreatine; Phosphorus Isotopes; Predictive Value of Tests; Protons; Risk Assessment

Cerebral apparent diffusion coefficients (ADCs) were determined in nine newborn piglets before and for 48 h after transient hypoxia-ischemia. Phosphorus MRS revealed severely reduced cerebral energy metabolism during the insult and an apparently complete recovery 2 h after resuscitation commenced. At this time, mean ADC over the imaging slice (ADCglobal) was 0.88 (0.04) x 10(-9) m2 x s(-1) (mean (SD)), which was close to the baseline value of 0.92 (0.4) x 10(-9) m2 x s(-1). In seven of the animals, a "secondary" failure of energy metabolism then evolved, accompanied by a decline in ADCglobal to 0.64 (0.17) x 10(-9) m2 x s(-1) at 46 h postresuscitation (P < 0.001 versus baseline). For these seven animals, ADCglobal correlated linearly with the concentration ratio [phosphocreatine (PCr)]/[inorganic phosphate (Pi)] (0.94 < r < 0.99; P < 0.001). A nonlinear relationship was demonstrated between ADCglobal and the concentration ratio [nucleotide triphosphate (NTP)]/[Pi + PCr + 3 NTP]. The ADC reduction commenced in the parasagittal cortex before spreading in a characteristic pattern throughout the brain. ADC seems to be closely related to cerebral energy status and shows considerable potential for the assessment of hypoxic-ischemic injury in the newborn brain.

Topics: Animals; Animals, Newborn; Asphyxia Neonatorum; Blood-Brain Barrier; Body Water; Brain; Brain Damage, Chronic; Brain Edema; Diffusion; Humans; Hypoxia, Brain; Image Processing, Computer-Assisted; Infant, Newborn; Magnetic Resonance Spectroscopy; Phantoms, Imaging; Phosphates; Phosphocreatine; Swine

Studies of the brains of severely birth-asphyxiated infants using proton (1H) magnetic resonance spectroscopy (MRS) have shown changes indicating a rise in cerebral lactate (Lac) and a fall in N-acetylaspartate (Naa). The aim of this study was to test two hypotheses: 1) that these changes can be reproduced in the newborn piglet after transient reversed cerebral hypoxiaischemia, and their time course determined; and 2) that changes in Lac peak-area ratios are related to changes in phosphorylation potential as determined by phosphorus (31P) MRS. Eighteen piglets aged < 24 h were anesthetized and ventilated. Twelve underwent temporary occlusion of the carotid arteries and hypoxemia, and six served as sham-operated controls. 1H and 31P spectra were acquired alternately, both during the insult and for the next 48 h, using a 7-tesla spectrometer. During hypoxiaischemia, the median Lac/total creatine (Cr) peak-area ratio rose from a baseline of 0.14 (interquartile range 0.07-0.27), to a maximum of 4.34 (3.33-7.45). After resuscitation, Lac/Cr fell to 0.75 (0.45-1.64) by 2 h, and then increased again to 2.43 (1.13-3.08) by 48 h. At all stages after resuscitation Lac/Cr remained significantly above baseline and control values. Naa/Cr was significantly reduced below baseline and control values by 48 h after resuscitation. The increases in the Lac peak-area ratios were concomitant with the falls in the [phosphocreatine (PCr)*]/ [inorganic phosphate (Pi)] ratio, during both acute hypoxiaischemia and delayed energy failure. The maximum Lac/Naa during delayed energy failure correlated strongly with the minimum [nucleotide triphosphate (NTP)]/[exchangeable phosphate pool (EPP)] (r = -0.94, p < 0.0001). We conclude that both hypotheses have been confirmed.

Topics: Animals; Animals, Newborn; Aspartic Acid; Asphyxia Neonatorum; Brain; Creatine; Energy Metabolism; Humans; Hydrogen; Hypoxia, Brain; Infant, Newborn; Ischemic Attack, Transient; Kinetics; Lactates; Magnetic Resonance Spectroscopy; Phosphocreatine; Phosphorus; Reperfusion; Swine; Time Factors

Regional cerebral metabolite concentrations, principally of choline-containing compounds (Cho), total creatine (Cr), N-acetylaspartate (Naa), and lactate (Lac), can be quantified by in vivo proton magnetic resonance spectroscopy. In order to estimate a metabolite concentration, it is often necessary to measure the transverse relaxation time (T2). Metabolite T2s depend on cytosolic viscosity: as [adenosine triphosphate] falls leading to Na+/K+ pump failure, cytosolic water increases and T2s lengthen. In central grey-matter in human infants, Naa may be almost exclusively neuronal: Naa T2 may index neuronal edema and energy generation. In this preliminary report, metabolite concentrations and T2s have been measured in central grey matter in human infants suspected of perinatal hypoxic-ischemic cerebral injury. In infants who developed serious cerebral injury or died, [Cho] and [Naa] were low (the latter suggesting neuronal loss), [Lac] and all metabolite T2s were increased: the Naa T2 increase possibly reflected neuronal edema following failure of energy generation in a fraction of remaining neurons.

Topics: Asphyxia Neonatorum; Brain; Humans; Infant; Infant, Newborn; Magnetic Resonance Spectroscopy; Phosphates; Phosphocreatine; Reference Values

Studies of cerebral oxidative metabolism were carried out by phosphorous magnetic resonance spectroscopy during the first week of life in 52 infants with clinical and/or biochemical evidence of birth asphyxia. 15 infants died and the 37 survivors were assessed by a wide range of neurodevelopmental tests at one year of age. The minimum recorded values for cerebral phosphocreatine/inorganic phosphate concentration ratio (an index of oxidative metabolism) were related to outcome. The results showed a significant relation between the extent of derangement of oxidative metabolism and the severity of adverse outcomes, including death, neurodevelopmental impairment and reduced head growth.

Topics: Adenosine Triphosphate; Asphyxia Neonatorum; Birth Weight; Brain; Brain Damage, Chronic; Energy Metabolism; Female; Follow-Up Studies; Gestational Age; Humans; Infant, Newborn; Infant, Premature, Diseases; Magnetic Resonance Imaging; Male; Neurologic Examination; Phosphates; Phosphocreatine

Twelve normal and 32 asphyxiated neonates were studied using global and depth resolved phosphorus magnetic resonance spectroscopy (31PMRS). Eight of the asphyxiated group died or survived with major neurodevelopmental abnormalities. A global phosphocreatinine/inorganic phosphate (PCr/Pi) ratio below the range of values from normal infants predicted adverse outcome after asphyxia with a positive predictive value of 64%, sensitivity 88%, and specificity 83%. Corresponding values for global inorganic orthophosphate/adenosine triphosphate (Pi/ATP) ratios were positive predictive value 88%, sensitivity 96%, and specificity 88%. Spatially localised MRS data, obtained using phase modulated rotating frame imaging, showed cerebral energy metabolism to be more abnormal in deep than superficial regions after birth asphyxia. However, in this population of full term infants none of the regional metabolite concentrations were superior to global data for prediction of outcome.

Topics: Adenosine Triphosphate; Asphyxia Neonatorum; Brain; Humans; Infant, Newborn; Magnetic Resonance Spectroscopy; Phosphates; Phosphocreatine; Phosphorus; Predictive Value of Tests; Prognosis; Sensitivity and Specificity

Surface coils with strong coupling for both 31P and 1H were used to measure metabolite concentrations by in vivo NMR spectroscopy. Tissue water was used as an internal concentration reference and the 31P and 1H spatial sensitivities of the coils were matched. For such coils, sample loading does not necessarily have a significant effect on absolute quantitation results. The coils had proportionality constants which were almost independent of loading and the 1H and 31P flip angles at the coil centre produced by fixed length pulses were approximately equal over the range of loading conditions encountered in vivo. For 7 normal infants, of gestational plus postnatal age (GPA) 35 to 37 weeks, the nucleotide triphosphate concentration in the cerebral cortex was 3.7 +/- 0.6 mmol/L wet tissue (mean +/- SD). Further studies of normal infants down to 26 weeks GPA indicated that phosphorus metabolite concentrations increased significantly with GPA during this period. Concentrations were often low in the cerebral cortices of birth asphyxiated infants. In order to provide corroboration for the results from neonatal brain, data were acquired also from the resting, unexercised forearm muscles of 6 young adults and the measured adenosine triphosphate concentration was 6.3 +/- 0.8 Mmol/L wet tissue.

Topics: Adenosine Triphosphate; Asphyxia Neonatorum; Brain Chemistry; Female; Humans; Infant; Infant, Newborn; Magnetic Resonance Spectroscopy; Male; Phosphates; Phosphocreatine

To investigate the prognostic significance of abnormalities of oxidative phosphorylation, the brains of 61 newborn infants born at 27-42 wk of gestation and suspected of hypoxic-ischemic brain injury were examined by surface-coil phosphorus magnetic resonance spectroscopy. Of these infants, 23 died, and the neurodevelopmental status of the 38 survivors was assessed at 1 y of age. Of the 28 infants whose phosphocreatine/inorganic orthophosphate (PCr/Pi) ratios fell below 95% confidence limits for normal infants, 19 died, and of the nine survivors, seven had serious multiple impairments (sensitivity 74%, specificity 92%, positive predictive value for unfavorable outcome 93%). Of the 12 infants with ATP/total phosphorus ratios below 95% confidence limits 11 died (sensitivity 47%, specificity 97%, positive predictive value 91%). Among the 46 infants with increased cerebral echodensities, PCr/Pi was more likely to be low, and prognosis poor, in infants whose echodensities were diffuse or indicated intraparenchymal hemorrhage than in infants whose echodensities were consistent with periventricular leukomalacia. We conclude that when reduced values for PCr/Pi indicating severely impaired oxidative phosphorylation are found in the brains of infants suspected of hypoxic-ischemic injury, the prognosis for survival without serious multiple impairments is very poor, and that when ATP/total phosphorus is reduced, death is almost inevitable.

Topics: Asphyxia Neonatorum; Brain Ischemia; Humans; Hydrogen-Ion Concentration; Infant, Newborn; Magnetic Resonance Spectroscopy; Nervous System; Organophosphorus Compounds; Oxidative Phosphorylation; Phosphates; Phosphocreatine; Phosphorus; Predictive Value of Tests; Prognosis

We studied the effect of respiratory acidosis (pH = 6.8) on mechanical function, tissue adenosine triphosphate (ATP), and effluent creatine kinase (CK) in isolated arterially perfused hypoxic newborn and adult rabbit hearts. In the oxygenated muscle, acidosis reduced tension (T) and maximal tension first derivative [+ dT/dt (max)] in the adult more than in the newborn. In the adult hypoxic and reoxygenated hearts, acidosis during hypoxia (not reoxygenation) improved the recovery of T, + dT/dt (max) and tissue adenosine triphosphate (ATP) and reduced CK release and the rise in the resting tension. In the newborn heart, respiratory acidosis during hypoxia had no beneficial effects on recovery of mechanical function, tissue ATP and CK release. The buffering capacity and sarcolemmal H-Na exchange rate are both higher in the newborn heart than in the adult heart. This suggests that acidosis reduces the rise in intracellular Na and Ca, that is observed during hypoxia and reoxygenation, in the adult more than in the newborn and this may explain the beneficial effect of acidosis in the adult and not in the newborn.

Topics: Acidosis, Respiratory; Adenosine Triphosphate; Age Factors; Animals; Animals, Newborn; Asphyxia Neonatorum; Creatine Kinase; Heart; Humans; Hypoxia; Infant, Newborn; Myocardium; Oxygen; Phosphocreatine; Rabbits

Phosphorus (31P) nuclear magnetic resonance spectroscopy was used to study intracellular metabolism in the brains of 6 normal newborn infants and 10 infants who had been asphyxiated during delivery. In the normal infants spectral peaks mainly attributable to adenosine triphosphate, phosphocreatine (PCr), phosphodiesters plus phospholipids, and inorganic orthophosphate (Pi) were always detected, together with an additional large peak in the phosphomonoester region indicating the presence of a metabolite or metabolites (probably largely phosphoethanolamine) which may be involved in rapid growth of the brain. In the asphyxiated infants, data obtained on the first day of life showed no differences from those in normal infants, but by the second to ninth days inverse changes in the concentrations of PCr and Pi had caused a significant reduction in PCr/Pi. This latency suggest the possibility of effective early treatment before irreversible metabolic damage sets in. Mean intracellular pH when PCr/Pi was minimal was 7.17 +/- 0.10. Values for PCr/Pi below 0.80 were associated with a very bad prognosis for survival and early neuro-developmental outcome.

Topics: Adenosine Diphosphate; Adenosine Triphosphate; Asphyxia Neonatorum; Brain; Energy Metabolism; Female; Humans; Hydrogen-Ion Concentration; Infant, Newborn; Magnetic Resonance Spectroscopy; Male; NAD; Phosphates; Phosphocreatine; Phosphorus; Spectrum Analysis

In vivo phosphorus nuclear magnetic resonance spectroscopy (31P NMR) was used to evaluate the pattern of phosphate compounds in seven newborn babies (mean gestational age, 32 weeks; birth weight, 1,430 gm; age, 37 days) with a history of perinatal asphyxia. Spectra were collected in a 1.9 Tesla superconductive magnet with surface coil techniques. The spectra had characteristic peaks for phosphorylated monoesters (PME), inorganic phosphate (Pi), phosphodiesters (PD), phosphocreatine (PCr), and ATP. In contrast to cortical spectra from mature animals, these newborn infant 31P NMR spectra were dominated by a large PME peak and had small PCr, Pi, and PD peaks. Intracellular pH, as measured from the chemical shift of the Pi peak relative to the PCr peak, was 7.1 +/- 0.1 (SD). We studied one infant postmortem, and a large PME peak was present in his spectrum. The presence of PME 3 hours after death strongly suggests that it is not a sugar phosphate. In NMR spectroscopy, compounds are identified by their chemical shift relative to a known standard (PCr); the chemical shift of the PME peak was 6.5 ppm, suggesting that it is a mixture of phosphoryl ethanolamine and phosphoryl choline. The PCr/Pi ratio (1.3 +/- 0.7) and the PCr/ATP ratio (0.7 +/- 0.4) were lower in these babies than in mature animals (greater than 2 and greater than 1.4, respectively); the PME/PD ratio (1.2 +/- 0.6), however, was much greater in the infants (mature animals, less than 0.2). These findings suggest that there are unique aspects of human newborn cerebral metabolites and bioenergetic reserve.

Topics: Adenosine Diphosphate; Adenosine Triphosphate; Asphyxia Neonatorum; Brain; Humans; Hydrogen-Ion Concentration; Infant, Newborn; Magnetic Resonance Spectroscopy; Phosphates; Phosphocreatine; Phosphorus

Intracellular metabolism in the brains of seven infants, born at 33-40 weeks' gestation and aged 44 h to 17 days, was studied on fourteen occasions by phosphorus nuclear magnetic resonance spectroscopy (31P NMRS). The characteristic spectral peaks of ATP, phosphocreatine (PCr), phosphodiesters, and inorganic orthophosphate (Pi) were always detected, together with a large peak attributed mainly to ribose-5-phosphate. The ratio of PCr to Pi NMRS signals (which are related to concentration) in one infant thought to have a normal brain was 1.7. In three infants who had severe birth asphyxia the PCr/Pi ratio ranged from 0.2 to 1.0 but increased as their clinical condition improved: infusions of mannitol solution caused a rapid increase in the ratio on four occasions in two of these infants. The PCr/Pi ratio was 1.4 in an infant with congenital cerebral atrophy and 0.7 in an infant with meningitis. Grossly abnormal 31P spectra antedated the detection by ultrasound of large porencephalic cysts in two infants. No systematic changes in intracellular pH (calculated from the chemical shift of the Pi resonance) were observed: the mean value for all observations was 7.2 +/- SD 0.1 (n = 14).

Topics: Adenosine Triphosphate; Asphyxia Neonatorum; Brain; Female; Humans; Hypoxia, Brain; Infant, Newborn; Infant, Newborn, Diseases; Magnetic Resonance Spectroscopy; Male; Phosphocreatine; Phosphorus; Ribosemonophosphates; Spectrum Analysis