title: Proton magnetic resonance spectroscopy of the brain during acute hypoxia-ischemia and delayed cerebral energy failure in the newborn piglet.
abstract: 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.
authors.affiliation: Department of Paediatrics, University College London School of Medicine, United Kingdom.
authors.forename: J
authors.initials: J
authors.lastname: Penrice
authors.forename: A
authors.initials: A
authors.lastname: Lorek
authors.forename: E B
authors.initials: EB
authors.lastname: Cady
authors.forename: P N
authors.initials: PN
authors.lastname: Amess
authors.forename: M
authors.initials: M
authors.lastname: Wylezinska
authors.forename: C E
authors.initials: CE
authors.lastname: Cooper
authors.forename: P
authors.initials: P
authors.lastname: D'Souza
authors.forename: G C
authors.initials: GC
authors.lastname: Brown
authors.forename: V
authors.initials: V
authors.lastname: Kirkbride
authors.forename: A D
authors.initials: AD
authors.lastname: Edwards
authors.forename: J S
authors.initials: JS
authors.lastname: Wyatt
authors.forename: E O
authors.initials: EO
authors.lastname: Reynolds
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D001238:Asphyxia Neonatorum; D001921:Brain / Q000378:metabolism*; D003401:Creatine / Q000378:metabolism; D004734:Energy Metabolism; D006801:Humans; D006859:Hydrogen; D002534:Hypoxia, Brain / Q000378:metabolism*; D007231:Infant, Newborn; D002546:Ischemic Attack, Transient / Q000378:metabolism*; D007700:Kinetics; D007773:Lactates / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D010725:Phosphocreatine / Q000378:metabolism; D010758:Phosphorus; D015424:Reperfusion; D013552:Swine; D013997:Time Factors
chemical_list: D007773:Lactates; D010725:Phosphocreatine; D010758:Phosphorus; D001224:Aspartic Acid; D006859:Hydrogen; C000179:N-acetylaspartate; D003401:Creatine