“Effect of MgSO₄ on cerebral energy state and intracellular Mg(Mg_i) during and following Hypoxic-Ischemia (HI)” † 1012

The mechanism of neuroprotection associated with Mg administration remains unclear; increases in Mg_i and attenuation of hypoxic-ischemic changes in brain energy state are two possibilities. To determine if Mg infused animals have higher Mg_i during and following HI and less alteration in brain energy state, MgSO₄ infused piglets (Mg, n=5, age 6±2 days, wt 1.5±0.3 Kg) (mean±SD) were compared to Na₂SO₄ infused piglets (Na, n=5, 5±3 days, 1.0±0.2 Kg) using P-31 MRS. After a control period, MgSO₄ (275 mg/kg over 30 min followed by 100 mg/kg over 30 min) was infused over 60 min to achieve hypermagnesemia (plasma [Mg] at 60 min = 9.12±1.49mM). The Na group received comparable volumes of Na₂SO₄ (plasma [Mg] at 60 min = 0.96±0.51mM). Both groups underwent HI (FiO₂=.08, bilateral carotid occlusion, hemorrhagic hypotension) over the last 15 min of infusions. During HI mean arterial pressure was 42±11 and 45±9% of control for Mg and Na, respectively, and O₂ content was comparably reduced from 10.3±1.7 to 2.3±0.8, and 9.7±0.5 to 3.0±0.6 vol% for Mg and Na, respectively. Mg_i, calculated from the ³¹P chemical shifts of NTP, was identical in each group at control (Mg, 0.22±03mM vs Na, 0.22±.01mM), increased to higher values during HI in Mg compared to Na (Mg, 0.55±.10mM vs Na, 0.46±.10 mM p<.05), and remained higher in Mg vs Na for 30 min post-HI. Intracellular pH (pH_i) was similar at control (Mg,6.99±.03 vs Na, 7.01±.02), and Mg had greater acidosis during and for 40 min post-HI(p<.05). Maximal acidosis in each group occurred at 10 min post-HI (Mg, 5.95±.12 and Na, 6.11±.13). Mg compared to Na had greater reductions relative to control (latter set at 100%) in NTP during HI (Mg, 48±6% vs Na, 70±3% p<.001), larger increases in inorganic phosphate (Mg, 248±49% vs Na, 144±20% p<.01), but similar changes in phosphocreatine. Group differences in NTP persisted over 20 min post-HI. Hypermagnesemia during HI increases Mg_i above elevated values with HI alone, but also results in greater decreases in brain energy state and more severe intracellular acidosis. Although increases in Mg_i may in part be a reflection of increased cerebral acidosis and reduction in NTP, the entry of the infused Mg into brain cells remains a possible mechanism by which Mg could modulate the detrimental effects of HI. Alternatively, the unexpected exacerbation in changes by HI in brain NTP and pH_i observed in Mg animals could be detrimental and requires further study.