The effects of systemic magnesium sulfate infusion on brain magnesium concentrations and energy state during hypoxia-ischemia in newborn miniswine.
The mechanism of neuroprotection associated with systemically administered magnesium remains unclear. This investigation examined the acute effects of systemically administered MgSO4 on brain extracellular ([Mg]ecf) and intracellular ([Mg]i) fluid Mg concentrations, specific brain phosphorylated metabolites, and brain intracellular pH. Miniswine were studied with P-31 magnetic resonance spectra, to derive [Mg]i, and brain microdialysis probes, to measure [Mg]ecf. Animals were infused with MgSO4 (n = 5, 275 mg/kg over 30 min followed by 100 mg/kg over 30 min, designated MgHI) or Na2SO4 (n = 5, designated NaHI), and both groups underwent hypoxia-ischemia (HI) over the last 15 min of the infusions. Groups differed in plasma [Mg] at the completion of HI (9.1 +/- 1.5 versus 1.1 +/- 0.6 mM for MgHI and NaHI, respectively, p < 0.05). MgHI had elevations of [Mg]ecf (0.23 +/- 0.11 and 0.40 +/- 0.14 mM at control and completion of HI, respectively), and [Mg]ecf was unchanged for NaHI (p < 0.05 versus MgHI). At the completion of HI, MgHI had greater decreases in nucleoside triphosphate (NTP) (48 +/- 6% of control), and more brain acidosis after HI (6.01 +/- 0.07) compared with NaHI (NTP, 70 +/- 3% of control; brain pH, 6.51 +/- 0.14, both p < 0.05 versus MgHI). [Mg]i increased to elevated values during HI in both MgHI and NaHI (p < 0.05 versus control of each group) and remained higher in MgHI over the next 25 min (p < 0.05 versus NaHI). There were inverse correlations during HI between [Mg]i and brain NTP (r2 = 0.73 and 0.59 for MgHI and NaHI, respectively), and brain acidosis (r2 = 0.85 and 0.85 for MgHI and NaHI, respectively) in each group. These findings indicate complex effects of Mg on the brain. Elevation of [Mg]ecf may be beneficial with regards to excitatory neurotransmitters. However, greater disturbance of brain NTP concentration, more acidosis, and the increase in [Mg]i may offset any benefit. The results warrant further investigation using indicators of neuronal injury to determine whether Mg supplementation provides neuroprotection.
Gee
Jerry B
JB
Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX 75390-9063, USA. abbot.laptook@utsouthwestern.edu
Corbett
Ronald J T
RJ
Perlman
Jeffrey
J
Laptook
Abbot R
AR
D000818:Animals; D000831:Animals, Newborn; D000927:Anticonvulsants / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002245:Carbon Dioxide / Q000097:blood; D004734:Energy Metabolism; D006863:Hydrogen-Ion Concentration; D020925:Hypoxia-Ischemia, Brain / Q000188:drug therapy* / Q000378:metabolism*; D008274:Magnesium / Q000378:metabolism*; D008278:Magnesium Sulfate / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D010100:Oxygen / Q000097:blood; D010766:Phosphorylation; D013552:Swine; D013556:Swine, Miniature
D000927:Anticonvulsants; D002245:Carbon Dioxide; D008278:Magnesium Sulfate; D008274:Magnesium; D010100:Oxygen