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.

The Effects of Systemic Magnesium Sulfate Infusion on Brain Magnesium Concentrations and Energy State During Hypoxia-Ischemia in Newborn Miniswine

“…Magnesium administration either before or after HI, ischemia, or excitotoxic exposure in perinatal and adult rats ameliorated the extent of neurologic injury (38 -43). In contrast, systemic magnesium administration after HI in newborn piglets did not prevent the development of delayed energy failure, but much lower [Mg] plasma were achieved compared with the present study (44). Furthermore, systemic magnesium administration after asphyxia in fetal sheep did not reduce the extent of cytotoxic edema, did not improve the recovery of the EEG, and did not alter the histologic outcome (45).…”

Magnesium Sulfate Treatment after Transient Hypoxia-Ischemia in the Newborn Piglet Does Not Protect against Cerebral Damage

“…Previous results from this study demonstrated that administration of MgSO 4 failed to reduce the delayed decline in cerebral energy metabolism after HI in newborn piglets (9). However, from the apparent success of MgSO 4 in protection against cortical injury induced by glutamate agonists (10), we surmised that local neuroprotective effects might also be expected in cerebral HI, even if global energy metabolism was unaffected.…”

“…The physiologic, MRS, and blood [Mg 2ϩ ] results have been published previously (9). In brief, there were no significant differences between the two groups of piglets for observations of a wide range of systemic and biochemical variables, including arterial PO 2 , PCO 2 , pH, base excess, hematocrit, blood glucose, mean arterial blood pressure, heart rate, rectal and tympanic temperatures, and plasma Na ϩ , K ϩ , urea, creatinine, and lactate, either at baseline, at the end of the insult, or 2, 24, and 48 h after resuscitation.…”

A Pilot investigation of mild hypothermia in neonates receiving extracorporeal membrane oxygenation (ECMO)

“…150 In a further study in newborn piglets, Greenwood et al151 reported that following hypoxic -ischaemia there was no difference in the severity of cerebral damage between piglets treated with magnesium sulphate and the placebo group.…”