title: Delayed ("secondary") cerebral energy failure after acute hypoxia-ischemia in the newborn piglet: continuous 48-hour studies by phosphorus magnetic resonance spectroscopy.
abstract: Phosphorous (31P) spectra from the brains of severely birth-asphyxiated human infants are commonly normal on the first day of life. Later, cerebral energy failure develops, which carries a serious prognosis. The main purpose of this study was to test the hypothesis that this delayed ("secondary") energy failure could be reproduced in the newborn piglet after a severe acute reversed cerebral hypoxic-ischemic insult. Twelve piglets were subjected to temporary occlusion of the common carotid arteries and hypoxemia [mean arterial PO2 3.1 (SD 0.6) kPa]. Mean cerebral phosphocreatine concentration [PCr]/inorganic orthophosphate concentration [Pi] decreased from 1.40 (SD 0.29) to 0.01 (SD 0.02), and nucleotide triphosphate concentration [NTP]/exchangeable phosphate pool concentration [EPP] decreased from 0.19 (SD 0.02) to 0.06 (SD 0.04) (p < 0.001 for each decrease). On reperfusion and reoxygenation of the brain, mean [PCr]/[Pi] and [NTP]/[EPP] returned to baseline. Observations continuing for the next 48 h showed that [PCr]/[Pi] again decreased, in spite of normal arterial PO2, mean arterial blood pressure, and blood glucose, to 0.62 (SD 0.61) at 24 h (p < 0.01) and 0.49 (SD 0.37) at 48 h (p < 0.001). [NTP]/[EPP] also decreased, but to a lesser degree. Intracellular pH remained unchanged. These findings appeared identical with those seen in birth-asphyxiated human infants. No changes in cerebral metabolite concentrations took place in six control piglets. The severity of secondary energy failure, as judged by the lowest [PCr]/[Pi] recorded at 24-48 h, was directly related to the extent of acute energy depletion, obtained as the time integral of reduction in [NTP]/[EPP] (p < 0.0001). This animal model of secondary energy failure may prove useful for testing cerebroprotective strategies.
authors.affiliation: Department of Paediatrics, University College London, United Kingdom.
authors.forename: A
authors.initials: A
authors.lastname: Lorek
authors.forename: Y
authors.initials: Y
authors.lastname: Takei
authors.forename: E B
authors.initials: EB
authors.lastname: Cady
authors.forename: J S
authors.initials: JS
authors.lastname: Wyatt
authors.forename: J
authors.initials: J
authors.lastname: Penrice
authors.forename: A D
authors.initials: AD
authors.lastname: Edwards
authors.forename: D
authors.initials: D
authors.lastname: Peebles
authors.forename: M
authors.initials: M
authors.lastname: Wylezinska
authors.forename: H
authors.initials: H
authors.lastname: Owen-Reece
authors.forename: V
authors.initials: V
authors.lastname: Kirkbride
mesh_terms: D000208:Acute Disease; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000378:metabolism*; D004734:Energy Metabolism / Q000502:physiology*; D002534:Hypoxia, Brain / Q000378:metabolism*; D002546:Ischemic Attack, Transient / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D008991:Monitoring, Physiologic; D010759:Phosphorus Isotopes; D013552:Swine; D013997:Time Factors
chemical_list: D010759:Phosphorus Isotopes