title: Magnesium sulfate after transient hypoxia-ischemia fails to prevent delayed cerebral energy failure in the newborn piglet.
abstract: Severely birth-asphyxiated human infants develop delayed ("secondary") cerebral energy failure, which carries a poor prognosis, during the first few days of life. This study tested the hypothesis that i.v. magnesium sulfate (MgSO4) after severe transient cerebral hypoxia-ischemia decreases the severity of delayed energy failure in the newborn piglet. Twelve piglets underwent temporary occlusion of the common carotid arteries and hypoxemia. Resuscitation was started when cerebral [phosphocreatine (PCr)]/[inorganic phosphate (Pi)], as determined by phosphorus magnetic resonance spectroscopy, had fallen virtually to zero, and nucleotide triphosphate (NTP) had fallen below a third of baseline. The piglets were randomized to receive, blind, either: 1) three i.v. infusions of 12.5% MgSO4 heptahydrate solution: 400 mg.kg-1 MgSO4.7H2O starting 1 h after resuscitation, and 200 mg.kg-1 12 and 24 h later (n = 6); or 2) three infusions of placebo, 0.9% NaCl (n = 6). Phosphorus and proton spectroscopy were continued until 48 h after resuscitation, and values were compared between the two groups. Mean plasma magnesium levels, 1 h after each of the three doses of MgSO4, were 2.1, 2.0, and 1.9 mmol.L-1, respectively. The severity of the primary insult, determined by the time-integral of depletion of cerebral [NTP]/[exchangeable phosphate pool (EPP)], was similar in the MgSO4-treated and placebo groups. After resuscitation, there was no difference in the progression or severity of delayed energy failure between the two groups, as judged by cerebral [PCr]/[Pi], [NTP]/[EPP], or lactate/creatine and N-acetylaspartate/creatine peak-area ratios. We conclude that MgSO4 did not decrease the severity of delayed cerebral energy failure.
authors.affiliation: Department of Paediatrics, University College London Medical School, United Kingdom.
authors.forename: J
authors.initials: J
authors.lastname: Penrice
authors.forename: P N
authors.initials: PN
authors.lastname: Amess
authors.forename: S
authors.initials: S
authors.lastname: Punwani
authors.forename: M
authors.initials: M
authors.lastname: Wylezinska
authors.forename: L
authors.initials: L
authors.lastname: Tyszczuk
authors.forename: P
authors.initials: P
authors.lastname: D'Souza
authors.forename: A D
authors.initials: AD
authors.lastname: Edwards
authors.forename: E B
authors.initials: EB
authors.lastname: Cady
authors.forename: J S
authors.initials: JS
authors.lastname: Wyatt
authors.forename: E O
authors.initials: EO
authors.lastname: Reynolds
mesh_terms: D000208:Acute Disease; D000818:Animals; D000831:Animals, Newborn; D004734:Energy Metabolism / Q000187:drug effects*; D002534:Hypoxia, Brain / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D007262:Infusions, Intravenous; D015640:Ion Channel Gating; D002546:Ischemic Attack, Transient / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D008278:Magnesium Sulfate / Q000627:therapeutic use*; D009682:Magnetic Resonance Spectroscopy; D013552:Swine; D016896:Treatment Outcome
chemical_list: D008278:Magnesium Sulfate